Podcast

Giancarlo Pruneri: Welcome to TJ Talks – Conversation about Oncology by Tumori Journal, the peer-reviewed oncology journal dedicated to the dissemination of key oncological themes and advancements. I am Professor Giancarlo Bruni, editor in chief of Tumori journal, and in this episode I am happy to meet Professor Andrea Sartori Bianchi, full Professor of Oncology at the University of Milan and director of the Division of Clinical Research and Innovation, Medical Oncologist at Grand Hospital Metropolitano Niguarda in Milan. Andrea, thank you for being with us today. 

Andrea Sartore Bianchi: Giancarlo, thanks so much for inviting me. 

Giancarlo Pruneri: Andrea, no doubt you are one of the most important key opinion leaders in colon cancer. Could you tell us something about your educational and professional background? 

Andrea Sartore Bianchi:  Yes. So, I’m a medical oncologist., I work in the Niguarda cancer center, and I’m professor of oncology at University of Milano, and my journey in oncology, let’s say, started at the University of Pavia, where I completed my medical degree and also the specialization in oncology. Then I had a research experience at Brown University in Providence, Rhode Island, at the Division of Clinical Pharmacology of Professor Calabresi. And that really led me to the interface between the clinical and practice and the molecular research. Subsequently, I work in Niguarda hospital, mainly focusing on colon rectal cancer. So, my interest was always centered on, let’s say, on precision oncology, including both biomarkers on solid tissue and also liquid biomarkers, so liquid biopsy, CTDNA, to guide treatment decision and to improve clinical efficacy of oncological treatment. So, I always had the goal to make cancer care more personalized and dynamic, something that I think we will cover this is becoming to have some results in colon rectal cancer. 

Giancarlo Pruneri: Andrea this is a fantastic path taking together, you know, education and research and clinical care, and it’s also a very good news knowing that you are, you know, integrating your education in Italy and working here in order to get research insights to Italy and to our community.  And, Andrea, you mentioned that you and your team are authors of seminal works on precision oncology in colon cancer based on liquid biopsy. In your opinion, what is the current use of liquid biopsy in this setting and what are the future developments? 

Andrea Sartore Bianchi: Yes, you know right now I think that the real actual use of liquid biopsy is very limited in colorectal cancer, clinical practice, because mostly now we can rely on liquid biopsy when tumor tissue is not available or insufficient., and you can detect, rash mutation, for example, another molecular alteration on the blood instead of tissue, and also there is an application to guide Anti-egfr challenge. This is mentioned in ESMO guidelines and many guidelines. And this is also based on results from our group for example. But really I think that this is just the beginning because the real potential of liquid biopsy is really, you know, unfolding in several directions, and some of these are really exciting. And I would say that, for example, one of the most promising, of course, is detecting the minimal residual disease, MRD. This is one of the most promising applications, and the limit here is sensitivity, but you know that now we have the newer tests that are integrating methylation, fragmentation or also broader genomic coverage, like whole exome sequencing. Now we are starting to see also in ctDNA. So, this will definitely enhance the clinical application of liquid biopsy for MRD, I think, and this is very important for oncologists in colorectal cancer field, you know to drive and to guide prognostication, and at the end, also the use of adjuvant treatment. Then of course there are also other applications, for example, in rectal cancer also MRD is important because it can support upfront intensive treatment to aim to non-operative strategy, and under this regard, at Niguarda, we conducted the no-cut trial, and the results were presented at ESMO last year and the results important part in ctDNA for improving the prediction of complete response. And also, I would like to highlight how the newer adjuvant trial will, I think, really be impacted by ctDNA. Because with ctDNA, I think that we will aim to have personalized adjuvant treatment, because once you are focusing on a population of MRD positive patient, probably also some targeted agents that we know are not now used in the adjuvant setting, at the end probably will prove to be efficacious because you are aiming to the right population. 

Giancarlo Pruneri: Andrea, I fully agree with you that liquid biopsy is absolutely the new goal in precision oncology. What I always wondering is that now we are forced to switch from clinical trials to clinical practice, and this is something that is forcing us to revolutionize, you know, our infrastructures and the way we are working on precision oncology by integrating liquid biopsy in our clinical paths. In this regard, precision oncology is experiencing a technological and cultural revolution, as you just mentioned: how do you see scientific research in oncology and particularly in colon cancer evolving over the next five years? 

Andrea Sartore Bianchi: Well, yes, I think that we are definitely entering a new phase, as you are mentioning where possibly, you know, technology, biology and the clinical inside the clinical part will be more convergent. And possibly ctDNA will be crucial for this transition, I think. So, one of the main advancements, I think it will be, again, to have more and more ctDNA integrated as a routine tool. So, think about prognostication. I foresee that possibly on top of the TNM, we will have a, let’s say a B parameter, the B for blood B1 or B0, depending on the presence or absence of MRD after surgical resection. So, this will be, I think, an advancement and also many more applications of liquid biopsy for driving treatment, also in the metastatic setting. But this is diagnostic, this is a diagnostic advancement. On the treatment front I see some trends that I think will be more and more important over the next five years, I think that we are increasingly going to move target therapies earlier on in the treatment pathway, so, we are seeing this, for example, the first example is Braf inhibition. So, we very recently had this important data of the breakwater study where for the first time, we have a targeted therapy against an oncogene in colon-rectal cancer that is Braf. Now with results also from the very early part of the patient in first line, so, chemo plus encorafenibcetuximab. So, this is an application of precision oncology in first line, and I think that we will see more and more targeted therapy moving in this space earlier on in the treatment pathway. This is very important for rectal cancer, because there is a lot of heterogeneity, intratumor heterogeneity, so these accumulate over lines of treatment, and it’s more and more difficult to treat patients after first line. And, on the same side of treatment, I think that we will see more and more about RAS inhibition. This is a huge chapter of oncology in general, but also in colon-rectal cancer we have 50% of patients with RAS mutation and I think we will expand treatment beyond the G12c, but also we will be able to have newer drugs and with Pan-ras inhibitory activity, so this will be very, very impactful on the field. R2 also, you know that we our group provided first results about the R2 amplification and the possibility of having a treatment with a dual vertical blockade for the patient with R2 amplification, and I think that also here we will see results from first line treatments and possibly we will have sequencing in this patient.  

So, we have we will have more patients treated with Anti-R2 strategy receiving possibly more course of another Anti-R2 regimen, let’s say a rechallenge in this field, this is completely new. And finally, I think that one of the most important player will be the drug development, meaning that the targets are there, I think that we know about the most important genes that can be targeted, but we will have newer agents that are more impactful, and I think firstly to ADC antibody drug conjugates, so especially bispecific, and this may bring this new mechanism of action also to patients with colon-rectal cancer, and this I think will be very important also in this histology. 

Giancarlo Pruneri: Andrea, I mean, this is very fascinating because I think that what we are going to accomplish now is getting more and more reliable and robust in identifying the patients that should be treated with a molecularly driven therapies. And in the same time, for example, by using minimal residual disease, we could spare the side effects to patient with particular and, I mean, prognostic, and, you know, better prognostic, clinical course, so, I think that, you know, coupling these two approaches will be increasing, you know, the chance to be cured to our patients. As you know, Tumori Journal has promoted a discussion on the ethics of scientific publishing. What are the aspects of a scientific journal that you consider a priority when deciding to submit your work? 

Andrea Sartore Bianchi: Yeah, that’s a great question. It’s a very up-to-date topic, I think, because we have increasingly more and more journals every day, a lot of publications and also a lot of confusion in some for some aspect in clinical research and in also preclinical research. I think that what should be valuable and of course are the gold standard of scientific integrity, so the peer review process is so important. Also, there are issues also on this side from big journals in terms of having the proper compensation for a good review process. But this is, of course, very important. Also, I would say that I really appreciate those journals that foster interdisciplinary publication, interdisciplinary thinking. This is very important in oncology, and I think this is an aspect that is important. Of course, nowadays it’s important that a paper should be accessible, so accessibility is a key point for researchers to reproduce results. So, I appreciate of course, journals with open access options. And that’s important. And also, I have to say that it’s also nice to see, you know, journals becoming more engaged through social media, podcasts and other activities to, you know, to disseminate knowledge and, and results of paper.  

So, this is, I think, what Tumori is doing, what Giancarlo you are doing with your journal, and I think it’s very important because it really helps bring science closer to people, researchers, but also to communicate to the broad public and at the end, making communication of research more accessible and timely. 

Giancarlo Pruneri: I mean, Andrea, I completely agree. I mean, I think that what we are going to do is to keep discussing this issue because, you know, the ethics in publication is one of the most, uh, important and hot topics today. We have plenty of predatory journals, there is I mean, there is an editorial that came out in a Nature Medicine this month underlining the importance of choosing the right journal for publishing and for disseminating reliable data. Today we have discussed with Andrea about research and care and in, especially, in colon-cancer, but also in general we had, his view in the future of research in colon cancer. And, we have also discussing of, you know, life and attitude of the researcher Andrea Sartore Bianchi. And Andrea, I mean, thank you so much, it was really a pleasure having you on TJ talks. 

Andrea Sartore Bianchi: Thank you Giancarlo. It was a pleasure also by my side. Thank you so much! 

Giancarlo Pruneri: TJ talks is available on our website tumorijournal.org and on the podcast platforms. Follow us on X and LinkedIn to always be updated on cancer research and clinical practice in oncology. I’m Professor Giancarlo Pruneri, editor in chief of Tumori journal. Thanks for listening!

Lorenzo Ferrando: Welcome to TJ Talks – Conversation about Oncology by Tumori Journal, the peer-reviewed oncology journal dedicated to the dissemination of key oncological themes and advancements. I am Professor Lorenzo Ferrando, Section Editor at Tumori Journal, and in this episode I’m really happy to meet Professor Matteo Benelli, Associate Professor of Biochemistry at University of Florence. Matteo, thank you for being here with us today.

Matteo Benelli: Thank you, Lorenzo, for the invitation. It’s really a pleasure to be here and to talk with you about what I think is partly our shared passion.

Lorenzo Ferrando: Yes, indeed. So, Matteo, the first question for me would be what led you to specialize in bioinformatics?

Matteo Benelli: Well, thank you, Lorenzo, for the question. It was really an opportunity that happened by chance, I would say, because I was finishing my master’s degree in Nuclear Physics when I heard about a group at Careggi Universital Hospital that is the main hospital here in Florence that was offering a sort of predoctoral fellowship in what at the time was an emerging field, the bioinformatics. And I have to say that I didn’t know anything about bioinformatics at the time. But then, as you can imagine, studying nuclear physics, I had some programming experience because I knew how to analyze and interpret massive amounts of data. So, I took this opportunity and started working with R, a programming language that was new to me at the time and start analyzing data from high throughput technologies that it was back in 2008. So more than 15 years ago. And so, the dominant technology at the time were microarrays, then were followed by NGS. And after that, I joined an exciting PhD Program at University of Florence that was called Non-linear Dynamics and Complex Systems. That was really a multidisciplinary because we were physicists, biologists, psychologists, mathematicians that collaborate to study and solve complex systems. And you know that biological systems are maybe the most fascinating example of this complexity. So, to conclude, the course of the career that led them to specialize in bioinformatics, then after my PhD, I moved to the laboratory of Francesca De Michelis at University of Trento, because I wanted to really specialize in a specific field that is Cancer “Omics”. And that experience was incredible because it really shaped my approach to research. And the two years that I spent there were fantastic. I had the chance to contribute to really important studies primarily focus on advanced breast cancer. And I would say that consider that experience may be the most important one in defining my career, because after that I had clear ideas that I wanted to do exactly that work.

Lorenzo Ferrando: So, I think that it’s a very interesting and rich journey, like citing a very famous song. It’s a long way if you want to do bioinformatics basically. Right?

Matteo Benelli: Yes. Very long.

Lorenzo Ferrando: Yeah, but really exciting. So, you are the Co-Principal Investigator of AURORA, which is an international research program with a very important aim, which is improving the knowledge of the molecular mechanisms leading to response or resistance to therapy. Metastatic breast cancer patients are a very important effort from Europe and from several labs here in Italy, Belgium and Spain. So, what led you, what inspired you to join the AURORA program?

Matteo Benelli: Yes. You know, AURORA is an incredible effort and incredible project. And my involvement in AURORA is thanks to one person who changed the following course of my career, who was Angelo Di Leo. Because indeed, after completing my Postdoc at University of Trento, I moved to the oncology department at the hospital of Prato that was led at the time by Angelo, who was a really an internationally renowned breast cancer oncology. And he offered me an incredible, and I would say, unexpected opportunity that was to establish my first lab, the focus on bioinformatics and cancer omics. And this was especially, um, surprising because Prato, that is my hometown, is known for its textile industry, not cancer research. And so, I took this opportunity and started my first lab there. And while I was running the lab, Angelo invited me to join AURORA as an expert bioinformatician because Angelo at the time played a key role in the Breast International Group, that is the organization that coordinates this study and working on AURORA. You know, Lorenzo also, I think is and was at the time an exciting experience because it brings together a multidisciplinary team of clinicians, molecular biologists, bioinformaticians, pathologists. And the project is unique because, as you mentioned before, it provides access to primary tumor metastasis. And we generated the data multi-omics profiling of these samples to better understand how breast cancer develops resistance to human therapies, and which are the molecular alterations that characterize metastasis. At the beginning, we work very hard for two, maybe three years, and our work led to the first publication of this project that was published in Cancer Discovery. So, what was the path that led me to assume the role of Pi? This was quite incredible for me because at the time, AURORA was led by two clinical co-pis. And after the manuscript was published, I think that, you know, our work received recognition. And I think that it became clear to the Breast International Group that a more technical, non-clinical lead, was also essential to move the project forward. And so I was invited to join AURORA as also as Co-pi.

Lorenzo Ferrando: Yeah. I think that the fact that you join the AURORA program as Co-pi is like a great opportunity for the right person, the right moment for the right person. And I think that it is clear that bioinformatics is getting more and more central and relevant in this kind of cancer research. So how does bioinformatics, in your opinion, contribute to understanding the evolution of breast cancer, especially in identifying new therapeutic targets? And especially can you share if you can, of course, some of the most exciting findings that your team has made so far.

Matteo Benelli: Yes, I agree completely with you, Lorenzo. Bioinformatics has become an essential tool for studying cancer. AURORA is a prime example. And because I think because it enables to deal with the complexity of cancer. For instance, helping us to understand the emergence, the evolution, response to treatments, identifying new therapeutic targets, as you mentioned before. And this is because today cancer research relies on high throughput biotechnologies such as sequencing that we use every day, but also some new technologies that we are approaching in the in the last years that are imaging techniques that generate a data set, including thousands to millions of variables. And bioinformatics has the tools, the methodology that can deal with this complexity, but also enable to identify the most relevant features among these huge amounts of data. And the AURORA, which you mentioned before, is an example of how our expertise is essential in understanding how breast cancer develop resistance to therapy, for instance, because with our methodology, we are able to integrate multiple data to analyze simultaneously different layers of molecular information, such as genomics, transcriptomics. Because our goal in this project is to investigate molecular alterations acquired by tumors, to identify those that could be targeted by specific treatments. But in general, in addition to AURORA, the primary focus of the research of my group is in precision medicine, precision oncology. And among the most exciting findings you were referring to, I would like to mention that we work hard on circulating biomarkers. You know very well, particularly to the study of epigenetic alterations such as DNA methylation. We know, you know, that the liquid biopsy, especially the analysis of circulating tumor DNA. That is, these fragments of DNA released by tumors into the bloodstream is exciting and is an emerging tool for monitoring disease status in patients with cancer. So we are working on developing new methods that are both from the lab point of view, but also computational, obviously, that exploit these epigenetic features to improve the technical aspects of this test, so to improve sensitivity and specificity of this assay, but also to going beyond, because we would like in the future to have a phenotypic characterization from these non-invasive tests, a sort of capability that is only mainly done on tissue biopsy. We would like to have the possibility to do this also in a non-invasive way.

Lorenzo Ferrando: Yeah. I think that we could continue discussing this kind of topics for the entire day. I mean, it’s really exciting, but as you said, I think it’s a matter of complexity. I mean, informatics is just a very central part of cancer research, and it’s very complementary to the other domain of knowledge biology, medicine and bioinformatics as a tool to unlock the capability to answer very complex questions because technology is evolving like super-fast. The data generated is getting huge, really difficult to handle to manage. So, informatics has the tool to answer this kind of new wave of complexity. You know.

Matteo Benelli: I agree. And uh, maybe the most important term for us is, and for us, studying cancer is multidisciplinarity. So orthogonal and complementary skills. So, this is very important. Bioinformatics plays a key role in complementing the division.

Lorenzo Ferrando: Yeah. In fact, the next question I was thinking about would be how do you think bioinformatics will shape the future of personalized medicine? But now the question after listening to you is how is shaping the present right of personalized medicine?

Matteo Benelli: Yeah, I think that I agree with you that will and is playing a central role in cancer research and in personalized medicine. And let’s think about, for instance, the Molecular Tumor Board. Now are defined as multidisciplinary because they are, in terms of clinics, multidisciplinary. But imagine that in a near future these boards will involve clinicians as currently are involved in from different disciplines, but also molecular biologists, bioinformaticians that will help a clinician to interpret the results that they have, for instance, received from a comprehensive cancer gene panel test where hundreds of cancer genes are screened, but only few alterations are important to decide on the management of the patient. So, I think that this integration of our skills in these boards will happen soon. Hopefully soon, will happen for sure, but I hope also soon.

Lorenzo Ferrando: Yeah. You talked about the very hot topic here, the MTB right. Uh, let’s discuss a little bit about what does it mean to be a principal investigator, a Pi, in this country, in Italy. And how do you see the future of bioinformatics in this country? What are the challenges? You know, being performative and especially a principal investigator in bioinformatics?

Matteo Benelli: Yeah. So compared to the other countries that we know very well, Europe and also US, one consideration that we can do is that we are few.

Lorenzo Ferrando: True! Unfortunately, it’s true.

Matteo Benelli: Especially in relationship to the needs at least talking about the academic research. So, I think that this is due to the absence of specific academic course for sure, but also maybe most importantly, to the absence of a biotech industry, a solid biotech industry that is able to employ people with our skills out of academia. You know that being few can be seen as you are in a privileged condition because it’s easier to collaborate with other colleagues. But I think this has also some negative aspect related, for instance, to a limited competition that is usually not beneficial for improving the quality of the field. In some cases, your collaborators tend to consider you as a sort of service for their project. And this is really a problem for us because this situation limits the definition of bioinformatics as a valid research field. However, you know that being a Pi also means carrying on research projects and managing the lab, searching for funds. And I have to say that in Italy we are lucky because the Italian Association for Cancer Research is really a pillar for supporting us in our everyday work life, because they provide hundreds to thousands of researchers with the funding to conduct cancer research, including also researchers in the field of bioinformatics. And I am a recipient of a grant from ERC. So, I’m incredibly grateful for their support that they provide us for our activities. But, you know, regarding how I see the future of variable informatics in Italy, or last part of the question, I see it, I would say as bright because I’m optimistic for my group for sure, because I have a fantastic group of young researchers, both wet and dry, who work really with dedication and commitment. So, I am sure we will do some exciting work in the future. For the bioinformatics in general, I think it will be bright because the need for these skills will increase in the future. And I think also that we will assist a more balanced representation of computational water researchers in the in the future. But however, we also have to talk about some obstacles that we have in Italy. And we, Lorenzo, we discussed this a little bit in the past out of this podcast, because, you know, that Italy has some rigidity in the, in the system because it requires you to be, um, I mean, sort of labeled into specific categories, no disciplinary categories. So molecular biology, oncology, genetics, biochemistry. But our work is interdisciplinary per se. So, the categories do not easily apply to us. And we should work in some way to try to dismantle this bureaucratic rigidity and just let the research flow.

Lorenzo Ferrando: Yeah. I think that you touched a very relevant issue here because informatics being so hybrid, you know, touches different fields of from biology to medicine. So my hope and I think it’s your hope as well, is that in the future institutes the governments will be a little bit more elastic, let’s say, and will be more inclusive and maybe will Recognize officially in public institutes, hospital, etc. the professional figure of the Bioinformatician, which is now a little bit, you know, it’s not that easy to include and offer a long term job as a Bioinformatician is in a public institute. So, let’s see how the future will shape this next generation figure of researcher.

Matteo Benelli: I agree, Lorenzo, I think it will happen with some delay, obviously, because we are in Italy, but this is a real need, so in some way will happen.

Lorenzo Ferrando: Yeah, the need is there. So, let’s see. In the meantime, technology advances and as you know better than me, everyone like everyone is talking about AI and its use. So related to bioinformatics, what is the role of AI in analyzing big data and in this case big genomic data? Are there any emerging technologies or approaches that you are particularly excited about?

Matteo Benelli: Yeah, I agree with you that today AI has pervaded our language because everything is AI, but maybe nothing is important. Or I would say cool without AI, you know, you can stay out of AI because we have seen incredible stories of success of using AI in medicine, pathology, genomics. But these results have created an enormous hype around AI and obviously in our field. So, I think that we were in some way experts of AI, and we have always worked with different forms of AI, including also the classical machine learning, for instance, in the past. We have unethical role in not promoting too much AI. For instance, in cases where AI is not needed because you know that in some way it can be, AI has some disadvantages compared to other more classical approaches. And I think that there are many also of these disadvantages. One maybe the most important is that it depends on training using a huge amount of data to train these that are called the models now that are the core of the AI. But these models now in particular, if you think about the diagnostic test that exploit AI are proprietary of private biotech companies that are the only that have the budget to create them. So, think about, for instance, our health system. This situation could create some issues related to the dependency that our health system can in some way have with this private company. So, to be clear, I am a fan and supportive of AI, but only when it is needed. In other cases, let’s try to stay with more simple and also explainable approaches, because also explainability is a huge problem. I think that we are going to lose with some AI approach in the future.

Lorenzo Ferrando: Again, super interesting topic here because AI is really pervasive. Like everyone can use it, but whenever you talk about AI in diagnostics and etc., there is no competition. There is this gigantic investment in private companies developing tools. And they are really, really, really hungry for new data. And it can happen sometimes that public hospital can sell data sometimes, not sell is not the right word, but you know there must be some regulation between these private companies hungry for new data, hungry to develop new models and the data, and the data are of the people. Right? It’s a very interesting but complicated.

Matteo Benelli: Also, I have no mention. I did not mention another maybe limitation with the AI. That is the I have some doubts about some the issue of reproducibility because AI works very well when the context is clearly defined. No? The models are built on some training data that depends on some specific, for instance, assays, some specific technologies. But is it possible to translate this assay from the central lab in these private companies to a hospital? So how the model translates and how the model performs when we translate from the private company to the hospital? This I think it’s an open question. It’s problematic for the future.

Lorenzo Ferrando: True. So, you are a professor at University of Florence. Your lab is plenty of brilliant young researchers and students, but your lab is not the most common bioinformatics lab in this country, right? So, there are not so many labs like yours. And what advice would you give to young researchers who want to enter this field?

Matteo Benelli: I would have many advices, but maybe the most important one is to be prepared to work at the boundaries of many disciplines and languages, because our main role, if I have to define a single one, is to first understand or ask ourself a diagnostic, clinical or molecular question, then exploit our skills, our knowledge to solve this problem using computational statistics and mathematical strategies. And then we have to translate back the results that we obtained to molecular biologists, clinicians and so. So, we have to learn multiple languages because a clear communication between the declinations, the molecular biologist, for instance, and us is essential because we have to reach together the goal of solving some clinical question. And knowing multiple languages means also knowing multiple disciplines, or at least the discipline bioinformatics is applied to. So, I would suggest to interested students, researchers coming from computer science, engineering, physics, mathematics, statistics, study biology or medicine. The other way around, for those coming from biology, biotechnology and medicine, study statistics and computer science.

Lorenzo Ferrando: Yeah, I think that you said it perfectly. I mean, don’t be afraid. One student studied biology, right? Okay. Now, after finishing the university, if you want to do bioinformatics, he must study statistics and sometimes can be, you know, let’s say not trivial, right? And the other way around. And in my opinion, sometimes it’s more difficult the other way around. So, a Stem guy wants to study a little bit of cancer biology. So, it’s difficult at the beginning, but it’s really rewarding.

Matteo Benelli: Yeah. You have to be very committed, dedicated. But I think that at the end the results are clear.

Lorenzo Ferrando: Yeah, absolutely. Matteo, we are going to the end of this very nice and super interesting conversation. But where can people follow your work and learn about these really exciting AURORA program?

Matteo Benelli: Oh yes. Lorenzo, thanks for the question. So, you can have a look at my research group on the website of my university department in Florence. The site is sbsc.unifi.it. You can follow me and all news about the research we are doing on LinkedIn, my personal page. While regarding AURORA, there are much information on the website of the Breast International group that coordinate the study. The website is big against cancer.org. If you are interested, you can read the first manuscript that was published on Cancer Discovery a few years ago. It’s very easy to retrieve from PubMed, Google scholar, first name is Philippe Aftimos. He’s a friend of mine and co-pi of the study. But also, for other many, many new exciting findings from AURORA, I am sure you will hear very soon.

Lorenzo Ferrando: So, to all the listeners, I really encourage to follow Matteo because there are some very interesting surprises, let’s say, or publication in the really next future. So, it has been my pleasure to have you here. Thank you so much for being with us on TJ Talks.

Matteo Benelli: Thank you again, Lorenzo. And it was really a pleasure also for me chatting with you.

Lorenzo Ferrando: In this episode we found out how bioinformatics is transforming oncology from understanding breast cancer at the molecular level to uncovering new therapeutic targets. Professor Matteo Benelli shared insights from the AURORA program and highlighted the impact of AI on personalized medicine. We also explored the future of bioinformatics in Italy and heard valuable advice for the next generation of researchers. TJ Talks is available on our website tumorijournal.org and on the best podcast platforms. Follow us on X and LinkedIn to always be updated on cancer research and clinical practice in oncology. I am Professor Lorenzo Ferrando, Section Editor at Tumori Journal. Thanks for listening!

Paola Perego: Welcome to TJ Talks – Conversations about Oncology by Tumori Journal, the peer-reviewed oncology journal dedicated to the dissemination of key oncological themes and advancements. I am Professor Paola Perego, Section Editor for Pharmacology of Tumori Journal. Over time, there has been a shift in understanding the mechanisms of drug resistance of tumors: from considering just the relevance of genetic features of tumor cells, to also thinking of their plasticity, driven by epigenetic mechanisms. And we also look at the tumor as an ecosystem composed by tumor cells and several players from The Tumor Microenvironment. To discuss approaches to overcome drug resistance in cancer, with reference to mechanisms and experimental models, I’m happy to welcome Professor Sven Rottenberg. Sven, thank you so much for joining us to TJ talks.

Sven Rottenberg: Hi, Paola. Thank you very much for inviting me.

Paola Perego: Sven, let me introduce you to our listeners. You are Chair of the Department of Infectious Diseases and Pathobiology at the University of Bern, where you are investigating cancer drug resistance. Your group studies “Genetically Engineered Mouse Models of Human Breast Cancer” uses drugs that are frequently employed in the clinic. Okay, here’s my first question: what are the key challenges when it comes to anti-cancer drug resistance?

Sven Rottenberg: Yeah, well, drug resistance is unfortunately still the most common cause of death of patients with metastasized cancer. So, for example, if you have a tumor with breast cancer, with a Her2 positive receptor, and there’s a targeted therapy, then challenges that often many of these patients do not respond upfront. So that’s a first key challenge in this response to predict which patients really benefit from a certain therapy. And then another big challenge is that those patients that do respond, that where the tumors basically melt down, that the tumor cells in these patients cannot be completely eradicated. So, you have a few residual cells that basically persist. And from these residual cells then tumors relapse. And that brings me to the third challenge is that these relapsing tumors then often show secondary resistance. So acquired resistance and no longer respond to the treatment.

Paola Perego: Sven, how can your models be useful to define drug resistance mechanisms and particularly their overcoming?

Sven Rottenberg: So basically, we work with genetically engineered mouse models. And that has the advantage that we can, under very defined conditions, introduce genetic alterations and study these in mice that have a fully functional immune system. And the advantage of the mouse models is also that there is less of this genetic variability that we see in patients, which makes it much more difficult to identify, clearly identify mechanisms in patients. Moreover, the clinical trials in patients are very expensive, and they are often not enough patients to test all the various combinations. So basically, I think that our models are complementary tool where we can first check what are the most promising approaches to overcome resistance. And then these can be further tested in clinical trials. Moreover, we also have in vitro tools, so we have 2D cell lines, also 3D organoids that we have derived from these models, and so in these we can also do functional genetic screens. While these functional genetic screens you often get many hits and you’re not exactly sure which of these hits is now really relevant in vivo setting. And there this overlay between these in vitro assays with our models I think is also a powerful combination to see which mechanisms are identified in vitro are really relevant in vivo.

Paola Perego: Sven, what type of treatments are you studying?

Sven Rottenberg: Well, we are using novel targeted inhibitors that are now also frequently used in the clinic. We also use immunotherapy. We are looking also at newly developed therapies, but we are also looking at classical chemotherapy and radiotherapy because they are still frequently applied in the clinic. And so basically, we are particularly interested in treatments that are really used in the clinic.

Paola Perego: So, is there a common mechanism that you find in your models and that we can target?

Sven Rottenberg: Well, unfortunately not really. So, it’s very interesting that even in our genetically defined models, we see that there are really many different ways how these tumors can acquire resistance. So, for example, many of the current anti-cancer therapies they target a defect in the repair of DNA damage. So many tumors have lost DNA repair pathways. That’s how additional mutations occurred. This is how the tumor evolved. And so, this one can target with different treatments. And often these tumors that lack this DNA repair are very sensitive and will really shrink substantially. However, they are not easily eradicated. And then the tumors regrow, become resistant, and in these resistant tumors we see that they now manage to deal with the DNA damage again. And they do that in very different ways. But, maybe if you want what is common about these mechanisms, is that basically the way how the cells can deal with the DNA damage well, has improved, but in very different ways.

Paola Perego: But why is it so difficult to eradicate tumors that are initially drug sensitive?

Sven Rottenberg: Yeah, that’s a very good question. And this is also really very interesting. And well, we think that there are several mechanisms behind that, and they are based on the intratumoral heterogeneity and also on the plasticity of the tumor cells, because the tumor cells can basically relatively easily go from one state to another. So, one mechanism in this resistance is, of course, that in the tumor upfront by chance, because of this large heterogeneity, there may already be some mutations present in some cells that give them an advantage during treatment. And then of course these cells will be selected out and be resistant. Another option is that these mutations occur then during the treatment and also then basically acquired. But what I find even more surprising is that there are tumors that are, well, that are even sensitive again, when the tumor relapses, but still the cells cannot be easily eradicated.

Paola Perego: How is this possible, Sven?

Sven Rottenberg: Well, yeah. So, there’s again a very good question. So basically, our research suggests that these persisting tumor cells, we call them “drug tolerant cells” are transiently lying low or hibernating, if you want, and thereby avoid the cell death, because the cell death is often inflicted when cells replicate their DNA. And basically, when these cells are lying low and then eventually the drug is gone, then they reenter the cell cycle. And we think that there are epigenetically regulated programs behind this involving reprogramming factors and chromatin remodeling.

Paola Perego: So, is there a role for the tumor microenvironment in this context?

Sven Rottenberg: Yes, absolutely. So, because it’s very well possible that the tumor microenvironment influences these epigenetic programs. And this is indeed part of our current investigations.

Paola Perego: This sounds somehow frustrating. Is there no way to kill this persisting tumor cells?

Sven Rottenberg: Well, in our model systems, we found that if sufficient DNA damage is inflicted, also the persisting cells will give in and eventually be eradicated. But of course, this high dose chemotherapy has obviously more side effects, and we are currently investigating new vulnerabilities of these persisting cells.

Paola Perego: How do you do this?

Sven Rottenberg: Well, we successfully managed to mimic these residual cells in 3D organoid cultures in vitro. And this gives us now a very useful tool to apply more high throughput genetic screens to test which genes are really essential for these residual cells to survive. And our hope is that, when we inhibit the proteins that are encoded by these genes, the tumors no longer relapse.

Paola Perego: It sounds like there is still a long way to go. Could results from your research be applied to the clinic?

Sven Rottenberg: Well, we work for example, with mouse models for Brca1 and Brca2. Brca2 mutated breast cancer, and in these we found that combination therapy where the tumors first treated with platinum based drugs, followed by a maintenance therapy with Parp inhibitors, is very promising, and this treatment approach could then indeed be proven to be also highly effective in patients with Brca1 or Brca2 mutated breast and ovarian cancer. And this has become now a standard of care for these specific tumor subtypes. Moreover, we have also identified a channel which is crucial for platinum drug uptake. So how the platinum drugs enter the cells. And we found that in some tumors this channel is dysfunctional. And then specific platinum drugs are not the best choice for these patients. Or because they do not enter the cells, they do not target the DNA, do not induce the damage then. And so, we are currently testing ways to identify these patients and look for other treatment options that might be better suited for these individual patients.

Paola Perego: If drug-resistance arises, one would hope that this comes at a cost for the resistant cells and there may be a new vulnerability that one can target.

Sven Rottenberg: Absolutely. This is indeed we find some or we find examples in our models where resistance to one type of therapy increases the sensitivity to another one. And finding such new vulnerabilities of the resistant tumor cells is an important part of our research.

Paola Perego: Do you think that this is the future of cancer therapy? When resistance comes up, administering new combinations of drugs that then make use of the new vulnerability gained.

Sven Rottenberg: Yeah. So, I think there will be definitely cases where this is useful, but unfortunately there is also the frequent clinical observation that tumors that have the acquired resistance are also resistant to all sorts of therapy. Showing this, a so-called pen resistance and the precise mechanisms behind this pen resistance are not entirely clear. So, one mechanism for tumors that originally have a defect in the DNA repair is certainly this restoration of the DNA repair function, like genetic reversion, the case of Brca1 and Brca2 mutations. Because if the Brca1 or Brca2 work again, of course there’s no longer this sensitivity to or increased sensitivity to DNA targeting or DNA damage inducing drugs. But basically, for many of the tumors, we still do not know exactly what this is and or what causes this pun resistance. And therefore, I think that our goal should really be to try to eradicate the tumors upfront during the initial cycle of the treatments and avoid that these tumors relapse and subsequently acquire this pen resistance. And so I therefore think that the understanding of why tumor cells in a sensitive tumor persist is very important to understand, and also to find ways how to specifically kill these residual tumor cells. I think this is really crucial to achieve the overall goal of really get fully tumor eradication.

Paola Perego: Sven, thank you so much for being with us on TJ Talks and good luck with your research.

Sven Rottenberg: Paola, it has been a pleasure. Thank you very much.

Paola Perego: TJ Talks is available on our website tumorijournal.org and on the best podcast platforms. Follow us on X and LinkedIn to always be updated on cancer research and clinical practice in oncology. I am Professor Paola Perego, Section Editor for Pharmacology of Tumori Journal. Thanks for listening!

Giancarlo Pruneri: Welcome to TJ Talks – Conversations about Oncology by Tumori Journal, the peer-reviewed oncology journal dedicated to the dissemination of key oncological themes and advancements. I am Professor Giancarlo Pruneri, editor in chief of Tumori Journal, and in this episode I’m happy to meet Arsela Prelaj, a thoracic oncologist who works at the National Cancer Institute of Milan and has recently become the director of the Artificial Intelligence for Oncology Lab. Arsela, thank you for being with us today. 

Arsela Prelaj: Thank you, Giancarlo, for inviting me in this fantastic podcast. 

Giancarlo Pruneri: First of all, I would like to share your story with your listeners. How did you become an oncologist and later on, the director of an artificial intelligence lab? 

Arsela Prelaj: Oh, thank you for this question. I think it’s a really funny story. So basically I am originally from Albania and I used to study in Rome and became a medical oncologist in Rome. And then I came here in Milan to practice my oncology, let’s say path as a thoracic oncologist. But however, I for my whole life I love math. So some years ago I wanted to do a PhD, and the idea, let’s say to do wet lab was a bit difficult, so I didn’t love so much wet Lab. So I love numbers and this is why I decided to focus more in dry. And I have seen, let’s say, different programs, including statistics. However, five years ago I saw this artificial intelligence PhD, and also inspired from my previous boss, Doctor Garassino, I started this interesting PhD, which I mean changed my life, I can say. 

Giancarlo Pruneri: And this is a very interesting and thank you for contributing to the development of science in our country. Listen, our listeners, they are very curious, you know, what activities do you carry out in your artificial intelligence lab? 

Arsela Prelaj: So basically, there are many activities that we are working on focused the AI on lab. It’s focused more in using AI techniques for oncology needs. Now I recently reorganized the lab, let’s say in this last year, because we have grown from 10 people to 30 people around. So it’s meant to be a joint research platform with Politecnico di Milano. And I divided the team in six different subgroups focusing in AI tools, the Radiomics group, the digital pathology group, also the translational AI, explainable AI, and more recently large language models. 

Giancarlo Pruneri: Wow, this is a fantastic Arsela. And listen, artificial intelligence has for sure enormous potential, but I’d like you to hear from you what are, in your opinion, three goals that artificial intelligence could achieve in the specific field of oncology over the next three years. 

Arsela Prelaj: Oh, this is a very good question. I mean, I hopefully let’s say I will focus on three goals. However, I really believe that not only in the next year, but also in the further years, there will be many fields that will be changed and started already to change. However, if we think about the short-term results, let’s say that the main focus for sure will be in practice the screening, because we have done a lot of advancements in terms of screening and the use of images such as radiomics images to differentiate, for example, between a good benign lesion or malignant lesion. The other very good piece of advancements, I think, is the digital pathology, which for example, with the recent advancements of foundation models, it has been very interesting to use all these labeled data that are spread within different cancer centers. And I think this can can be very relevant, for example, for a diagnostic task which are simple tasks, but also why not for the prognosis and prediction tasks. And the digital pathology is this next very relevant field. The other field, which I think will change within also the next year and is already changing the way we are using AI, is the large language models which are used, for example, in this case more for automatic tasks. For example how we can automatize data collection. Imagine how much efforts we put there now to insert our data one by one. So this can be really and not only for the data management but also for the administrative tasks. 

Giancarlo Pruneri: This is amazing Arsela. And of course, these are great opportunities for the future. But we know that there is always a downside, especially whenever you like to implement a new technology in medicine and in oncology in particular. So which are the current hurdles in the development of artificial intelligence in your field? 

Arsela Prelaj: So this is another very nice point. So I wanted to share with you I think that also here I can mention three points which are crucial in this case. The first one to my opinion is the digitalization process, which is not very easy because obviously we have to take a lot of decisions, for example, how we can build cool rooms, which are all these rooms with big hardwares within the hospitals. But on the other hand, we have also these cloud advancements. And so how we can use the cloud, let’s say possibility also to to run our tasks, so hard level tasks and the digitalization we know that have costs. However I believe that for sure in this case we will find a solution, at least to do big investments in long-term purpose. So this is the first one, the second one, which is another interesting point and I think still a very weak point is the ethical and legal frameworks, which to my opinion, it’s not only the simple things, because the ethical and legal frameworks are also linked with the normal data, not only with AI, but in field of AI, especially, for example, to adapt for the adoption of generative AI within clinical practice, we know that there are a lot of big advancements and logarithmic advancements in terms of oncology. And imagine the whole, for example, lawyers and all these persons can stay and can remain up to date among all these technologies. So I think this is a very big deal. And I think that putting more expertises and more, for example, lawyers that are dedicated only in these tasks can be a solution. And the third one is how we can adapt all these tools in clinical practice. I think this is one of the third and main point, and I think that, for example, with explainable AI and other techniques which try to explain doctors how these tools work and explain also the responsibilities in this case, I think this can can can be a type of solution. 

Giancarlo Pruneri: I completely agree with you Arsela. Beside the ethical and legal stuff for sure, implementing data storage within a hospital is for sure a tough task for the future. But you are drafting a brand new world where physicians will be interacting with artificial intelligence. In your view, what will be the relationship between doctors and artificial intelligence in the near future, and what benefits will patients gain from it? 

Arsela Prelaj: Oh, I think this is my favorite question, honestly, because I think that it’s very connected with the hurdle that we discussed before related to why we do not adapt today and we are not adapting very, very quickly today to the tools. I think that this interaction has a paradigm shift today. So what we are doing with AI is not only trying to develop them, not only trying to explain them, but also having the human in loop. So the human in this case gives some feedback to the AI tools that not only take the explanation, but also say if they are satisfied with these explanations. So one of the main things is that obviously the human in the loop and also the human feedback, so there is also this paradigm shift which I do not aim to high level of performance. But I would prefer maybe to have a lower performance in the tools but to have a very good explanation because this would allow me absolutely a very good adaptation. So this is the main point. I think that also, for example, the educational part, it’s very important because doctors need to be in the loop in the education and training, and they have to be specialized. For example, if we think about the radiologist, which is specialized and has to know a bit on radiomics and the same for the digital path and the oncologist, I think we need absolutely to exploit more and more the education, the training and the exchange between the two players. So the interaction of human and AI intelligence. 

Giancarlo Pruneri: This is absolutely fascinating, having a brand-new world in oncology where, you know, technology and doctors, they have a crosstalk. And this will be for sure benefiting our patients. So Arsela, thank you very much for being with us on TJ Talks. 

Arsela Prelaj: Thank you for inviting me. Thank you. 

Giancarlo Pruneri: In this episode, we found out how artificial intelligence is crafting the future of oncology. Arsela told us the hurdles in its implementation, but she learned how to overcome them to fully develop the oncology of the future. TJ Talks is available on our website tumorijournal.org and on the best podcast platforms. Follow us on X and LinkedIn to always be updated on cancer research and clinical practice in oncology. I’m Professor Giancarlo Pruneri, editor in chief of Tumori Journal. Thanks for listening. 

Luca Agnelli: Welcome to TJ Talks – Conversations about Oncology by Tumori Journal, the peer-reviewed oncology journal dedicated to the dissemination of key oncological themes and advancements. I’m Doctor Luca Agnelli, section editor in bioinformatics at Tumori Journal, and in this episode, I’m really glad to meet George Calin, professor at the MD Anderson Cancer Center in Houston in Texas. And first of all, hi, George, I’m happy to talk with you. Thanks for being here with us.

George Calin: Hi, Luca. My my pleasure to be here with you. And also because I was working years in Italy: “Piacere di essere con noi, è sempre un piacere parlare italiano e interagire con italiani. I miei migliori anni sono stati probabilmente a Ferrara quando ho imparato genetica molecolare”. It’s my pleasure to be with you. Thank you.

Luca Agnelli: Well, nice to start as such. So let me give a brief overview of your brilliant career, since we have to introduce you to our listeners. You earned your degree in medicine from the University of Medicine in Bucharest. And then you worked in Ferrara, you said before, by Massimo Negrini’s lab. And later you became a postdoc with the Carlo Croce at the Kimmel Cancer Center in Philadelphia and then at the Columbus University. And finally, in 2007, you joined the MD Anderson as a professor in experimental therapeutics. And now you currently serve in the Department of the Translational Molecular Pathology, in the Division of Pathology. I summarized also your primary research interests, I hope to do this correctly: the role of microRNAs and non-coding RNAs in human disease and cancers, the sepsis, the study of familial predisposition to cancers and last, but not certainly the least, you are the editor in chief of the non-coding RNA journal, where I collaborate with you as the section editor in bioinformatics as well. So a very impressive path, George.

George Calin: Thank you, luca. You are too kind. I think in life you have to be lucky. So I was lucky to be at the right moment, in the right place. And what I tell to my fellows, I had over 200 fellows in my lab in the last 20 years, is that parents you cannot choose. It’s unconditional love for parents in both directions. But the mentors, you can choose very carefully. And I had a huge privilege to have wonderful mentors in Romania, a great Cytogeneticist D. Stefanescu. Then I went in Italy, where Beppe Barbanti Brodanò and Massimo Negrini were wonderful mentors in Ferrara, and then in Kimmel Cancer Center, Carlo Croce. So I had a lot of wonderful training in my life. Then I was very lucky to have excellent fellows who work with me because, let’s be fair, they are the people who are working in the lab. They are our mind and our hands. You have to make them believe in what research you are doing, and also you have to you have to teach them that science is about making discoveries at first, but at the end, they are the ones who move forward the science and then push forward. So really, I was lucky. And also I never pay attention to the hours of working because I was initially a gastroenterologist and intensive care physician. So I’m used to work and work and work, and in fact, in the United States only the sky is the limit for science. So again, you are very kind. But I was really a lucky one. Thank you.

Luca Agnelli: Yeah, wonderful. George, could you repeat the number of fellows?

George Calin: Over 200, because I think I started in a communist country. You know, 1980s Romania was a communist country, and genetics was forbidden because it was done by reactionary Americans and Western people. So I learned by myself first years molecular genetics and genomics in cancer. So taking from here, the point was that I have to train as many people as I can to widespread the knowledge on microRNAs. And I was lucky to be with Carlo Croce as the first one who discovered microRNA involvement in cancer. So really we have to widespread, I would say, an excellent discovery and the opening of a new field in medicine and in genetics.

Luca Agnelli: Yeah, that’s fantastic, and it’s the first very important message of this podcast. The first question can only be about the event of the year, you know, the Nobel Prize in Medicine, awarded to Victor Ambros and Gary Ruvkun, and 2024 is the year of the Nobel Prize for all the people who study microRNAs and their role in the post-transcriptional regulation and their role in cancer. But now my question is not about the past, but about the future. What challenges does non-coding RNA research have to face today, in your opinion?

George Calin: So it’s a wonderful question and it’s also well timed because this week starts the Nobel Prize ceremonies in Karolinska, so Gary Ruvkun and Victor Ambros will be there. So it’s wonderful timing. And I think it’s one of the most well-deserved at a long listed Nobel Prize, because it took 31 years from the time of discovery and publication of the two cell papers until they got the word, so it’s a wonderful time for microRNAs and for the teams that work with Ambros and Ruvkun. So the past of microRNAs is wonderful because we know so many things on how microRNAs are functioning, how many microRNAs are in the human body, over 2500, how they are involved in cancer hallmarks and in any type of disease. What I think is important is in fact, what you ask: the future. And the future will be developed, in my opinion, on two different directions. One is a biomarker development, how we can use the microRNAs from all the tissues and most important, from all the body liquids (plasma, urine, cerebrospinal fluid) in order to identify early cancer occurrence, early metastasis, dormant cells, minimal residual disease and any other type of clinical characteristics. This is a big challenge because for proteins it took quite 50 years to have the first proteins as biomarkers for different type of diseases. The second, which I think is extremely important, is the therapeutics. And what is the issue with new therapeutics is the fact that all of us, we compare what we create new therapeutics with a huge success of checkpoint inhibitors. And in fact, checkpoint inhibitors are a revolution. I say that I’m very happy to be to be here and everything we are doing in non-coding RNAs from now on as therapeutics will be compared with this huge success. In 1997, scientists got Nobel Prize for siRNAs and only in 2020, the first clinical trial with siRNAs were very successful. So I anticipate in the next decade microRNAs will go into clinical practice. And I tell to all of you who are listening one idea: start developing small molecules targeting RNAs. It’s a strange idea. We develop small molecules for proteins. But you who are listening, if you are a chemist or if you are love science seem to the concept of targeting RNAs with small molecules. Why is this is an important concept? Seeing how many of your friends colleagues in Italy, in Romania, my home country, in the United States suffered because of Covid 19 is because Covid 19 is generated by a single strand RNA virus. What would be the outcome of Covid 19 if the scientific, society and medical world would have small molecules targeting RNAs from 2017-2018? Very many lives would be saved. So I think next ten years, next decade will be a bright future for microRNA therapeutics if we are thinking out of the box.

Luca Agnelli: Thank you. So biomarkers and therapeutics, and  I would also remember that you were among the the group that for the first time discovered microRNAs as agents of cancer in chronic lymphocytic leukemia with Carlo Croce. So it’s an important step also for your career. And I would just focus on your career since in your journey between clinical practice and the research, you moved across three completely different worlds, from Eastern Europe to Western Europe, Italy, and finally to the United States. And my question is, what are, in your opinion, the main differences that you can highlight and if present, what are the common threads?

George Calin: Thank you. So I would start with the second part. What is the common in all these three places where I was. I was in contact with people who really love science and teach me science, as I told you from Romania, cytogenetics. Then I moved in Italy, where I learned molecular biology, and I saw my first time in the life of a pipette under Massimo Negrini. And then I went to the famous Carlo Croce, where we discovered the involvement of microRNAs cancer. So I think the commonality was that I pick really people who were able to teach me what to do and how to do because they had a huge passion for science. Now, what are the differences? Certainly each place is different. I would say, you know, I love Romania because it’s a place where I was born and the place where I was trained in school and medical school. I love Italy because it’s a place where I learn molecular genetics and I love Italy also because of the very nice, nice personalities of Italians. And I think Italians are very creative people, including in science. This is why you Italians have so wonderful scientists all over the world. And certainly I love United States. It’s the second time in these meetings when I say it, because only the sky is the limit in science. The amount of of money, the amount of intellectual interest, the amount of outstanding colleagues who are surrounding you is unbelievable. It’s a critical mass of people who are living to make discoveries and to do science. Many of them are clinician scientists, physicians with a love, a passion for science. So I would say in life is good to know how to take what is the best from each of the places. And I was lucky, thanks also to the fact that I had a family surrounding me. I have very good friends. I remain very good friends with Massimo Negrini, a very good friend with Carlo Croce, a very good friend with Drago Stefanescu, and I was able to keep these relations for what, for over quite 35 years from now.

Luca Agnelli: Great. Now a question, apart from your research activity, what are the best memories for these places?

George Calin: So I think in Romania the best memories is family because that is the route that you take the genes and you move forward with the genes that you took from your family. In Italy certainly is a friendship and the warmth of the people and the beautiful way that Italians are living and are doing science. And in the United States, certainly the scientific accomplishments and scientific results.

Luca Agnelli: Good, nice. But now, a tricky question. Where did you drink the best wine?

George Calin: Italy, Barolo. I’m a big fan of Barolo. I’m a big fan of Barolo all the time. When we go here to restaurants, we are drinking Barolo, one of the finest wines in the world. And it has this a little bitterness to make you aware that the life has a good side, you know.

Luca Agnelli: Great choice. I said before that you are the editor in chief of a journal, the Noncoding RNA Journal, and I’m happy to collaborate with you there. And I would talk about your editorial activity since I have a challenge for you now. There’s a topic we have already discussed informally in front of a beer I can remember in another occasion that I’d like to bring it up again here for our listeners. The era of peer review in impacted journals has come to an end? Or does it remain the guiding criterion for research? And if it remains the guiding criterion, what tools do you think that might be necessary to address the major issues of these systems, for example, the endemic shortage of reviewers?

George Calin: It’s a very important question, and I have to tell you that my experience as editor is much larger as a non-coding RNA journal. So I am a senior editor to cancer research and molecular cancer research, to molecular oncology, to molecular cancer, to cancer therapeutics, and so on. So I try to contribute because I think editing and reviewing and helping your colleagues to improve their manuscripts is an important, an essential part of research activity. I think a way to solve this shortage is quite simple: to have a payment for reviews, because reviewing is a very professional activity. You have to spend hours in order to give a good advice to your colleagues. So journals are making a large amount of money on the fees. I don’t know if you know, but Nature Communication is publishing over 10,000 papers a year. Wonderful papers and so on, but each cost many thousand dollars, so I’m a big proponent of a payment for the reviewers, and of course the reviewers have to do the review in a more professional way, on the side with the timing on how much they spend for the review and so on. So this will, I think, be a solution. Other journals try to go with a double blind option so you don’t know who are the reviewers, you don’t know who are the authors. I don’t think this will increase the amount of reviewers who want to take the job. Now you have also the eLife type of approach: doesn’t matter if the reviewers agree or not, your paper is published not as accepted, but as submitted. Anyway, I think this is a big issue, an issue which will be accelerated by the increase of the number of journals which is, on one side, a beauty of new science. You don’t depend on the 10-20 major journals in the field, but also it’s a big challenge because you don’t know what are the journals who have a good reputation and the ones who will disappear. And I have to thank you, Luca, for for your activity in the editorial board of of non-coding RNA, because really we need dedicated people like you for this type of activity, which is very important because in science not only is making discovery important, not only training our our mentees, but also helping our colleagues to publish great papers. And the help is in a fair and detailed review, which will also assure the accuracy of data and publications.

Luca Agnelli: Yeah. Well, George, I have to thank you for the great opportunity that you have offered to me in the past. So it’s a reciprocal opportunity. But you faced three great issues, so the payment of reviewers, the idea of double blind peer review and the opportunity to publish in the form of, for example, bio archives, so the content is as such without any kind of review. Recently, in the world of non-coding transcripts, the amount of omics data has increased exponentially. This is my field in bioinformatics field in particular, I am very interested in this topic and from my perspective, from my point of view, the risk of false positive data and results has grown as well. And my question for you now is should we invest much more resources on producing data or maybe it’s better to invest resources in utilizing the data that we already have generated? What’s your opinion?

George Calin: It’s a very clever question, and my answer is we have to use both in both ways, not only to continue analyzing the data, but also to spending for additional generation of additional data. So the data that are already generated should be analyzed with a new type of in silico methods, and you can know you are on the top of the field, and you can develop such new methods daily. But further, there are new types of analyzing and generating omics data that were not not available years ago. For example, I moved from from experimental therapeutics to translational molecular pathology right during Covid 2020 because I anticipated a huge development of spatial transcriptomics and digital pathology and in fact, in the last year, in the last 12 months, there were developed a lot of pathology assays in which you can do single cell analysis on a geographical map of the slides. This was unbelievable and unanticipated two-three years ago. So the way in which the technologies are developing is absolutely extraordinary. So I would answer to your question in both ways. Use more effort for what was generated to analyze, and don’t forget to put a large amount of money in these new type of technology who really change the way the medicine is done.

Luca Agnelli: Yeah, thanks George, i totally agree with you. So finally I would like to to play a game with you for this podcast. The game is: who would you throw off a tower? And I will start with Richard Dawkins or Stephen Jay Gould?

George Calin: None of them I like both what they they said,punctual evolution and genes are extremely important, so I will keep them alive.

Luca Agnelli: Okay. J.K. Rowling or Emmanuel Carrère?

George Calin: I’ll throw off Carrère because who doesn’t love Harry Potter? Everybody loves Harry Potter. So Rowling will be with me.

Luca Agnelli: Okay, and last but not least, Rafael Nadal or Novak Djokovic?

George Calin: I’d say Nadal because I pride Djokovic because he is born in Eastern Europe and it’s much more difficult to achieve greatness born in a place where the resources are less and exactly in the years of forming new personalities, you have to live that reality of less money, less knowledge, less amount of training camps, different type of diet. Nadal is wonderful, but I pride Djokovic because he started from a place where really is difficult to grow at this number one greatness.

Luca Agnelli: Great, great. So thank you very much George for being with us in TJ Talks. It has been a pleasure to talk with you. And I do really hope to see you in Italy early. So it’s a sort of invitation for you to come here in Milan to talk about microRNAs and science. So thank you very much.

George Calin: Thank you very much. It was my pleasure. So grazie mille caro Luca and good luck with the Tumori Journal because journals are a very important. It’s a way to widespread the news to all the world.

Luca Agnelli: Grazie George, un abbraccio.

George Calin: Grazie di cuore. Buona giornata a tutti. Grazie, grazie.

Luca Agnelli: To close this episode, I would like to recap the first words said by George. I was lucky in my life, and I want to do the same with my fellows. More than 200 fellows, 230 fellows to spread the research and science in university, in academic context and all over the world. TJ Talks is available on our website tumorijournal.org and on the best podcast platforms. Follow us on the social networks to always be updated on cancer research and clinical practice in oncology. I am Doctor Luca Agnelli, Section Editor in Bioinformatics at Tumori Journal and thank you very much for listening.

Giancarlo Pruneri: Welcome to TJ Talks: Conversation about Oncology by Tumori Journal, the peer reviewed oncology journal dedicated to the dissemination of key oncological themes and advancements. I’m your host, Professor Giancarlo Pruneri, editor in chief of Tumori journal, and in this episode, I’m happy to meet Giuseppe Curigliano, MD, PhD, and chair of the Division of Early Drug Development at the European Institute of Oncology in Milan, Italy. Giuseppe is also full professor of oncology at the University of Milan School of Medicine, among other things. Hi Giuseppe, thanks for being here.

Giuseppe Curigliano: Thanks for inviting me, Giancarlo.

Giancarlo Pruneri: Giuseppe, in the last two decades, you have had a very active role in clinical care and research, focusing on drug discovery in phase one trials. Can you outline how research on innovative drugs has changed the landscape of oncology in the last few years, and what is foreseeable for the next future?

Giuseppe Curigliano: You know, I believe the most important revolution was the agnostic approach to drug development. Specifically, we developed a lot of umbrella trial and basket trial in which selection of patients is not based on the organ of origin, but is based specifically on the genetic alteration of the tumor. I just would like to remind to you that many new agents have been approved based on agnostic development pembrolizumab and nivolumab in patients with microsatellite instability, larotrectinib and entrectinib in patients with intra fusion gene. Recently, BRAF inhibitors for V600E mutation and also for RET fusion gene positive selpercatinib. So it’s really a revolution where you select patients based on a genomic alteration.

Giancarlo Pruneri: So and this is something that we can forsee as a switch from an a histology approach to a more mutational profiling approach. So tumor profiling with all the available omics to date, we are just sticking on genomics, but in the next future we will be probably introduced to transcriptomics and proteomics as well, is a crucial step for translational and clinical research, but unfortunately it is not widely distributed even in the US and Europe and of course, also in Italy. Giuseppe, how do you think biology can drive clinical trials and real world care and how we could implement NGS profiling within our clinical practice?

Giuseppe Curigliano: This is really an excellent question. What I believe we have is to think about a precision oncology program in any single country. So we need to think globally, but to act locally specifically. NGS is not available all over the world. But if you centralize genomic platform, of course you can think about sequencing tumors of our patients in one single site, and then generate a model of network where patients can be referred to single centers to receive treatment. So coming back to your question, how we can drive clinical trials in real world care, what I believe is that in the future we will have more real world trials. And specifically we have some examples, like in the Netherlands with the droop model in which you perform locally and NGS, and then you have a network of cancer center where patients can be allocated to experimental treatment or to agnostic treatment based on availability. This is a very complicated network to be built. We have many challenges. The first, of course, is economical sustainability that in some continent, like Latin America or Africa or also China is not so feasible. But the key problem is to generate a network: if you generate a network, this will be feasible everywhere.

Giancarlo Pruneri: So this is a fantastic view. I think that this is something that we discussed a lot in the past, and maybe it is becoming a reality in the next future. Of course, we have to implement the infrastructure of our institution and this is probably the next goal. Giuseppe, you are also, among other things I already mentioned, a very passionate mentor and teacher for medical students and postdocs. Could you briefly explain your opinion on the role of education in future precision oncology, and how we could work together in order to create new professionals working within these important disciplines?

Giuseppe Curigliano: You know, this is a very important question because this was one of my aim also in the ESMO presidential program. So we have actually a workforce shortage in cancer. There are some countries in the world where you don’t have Pathologist to review the slides of a patient with a cancer. You don’t have a radiation oncologist. And in the future I will also see very few medical oncologists. So what we need is to boost, of course, cancer doctors and to offer opportunities to very young people in order to build a career of clinician scientists. It’s crucial, really, to create and generate this new professional figure that is specifically a cancer doctor that also understands about precision oncology. In the future, we will have much more technology engaged in cancer treatment. And this can be related, of course, to the impact of NGS of digital pathology Multi-omics analysis, artificial intelligence. So we need to have some people that will take care in high volume comprehensive cancer center in a multi-dimensional approach to cancer care. And then we need to generate locally medical oncologists that of course, at least know the standard of care for any single disease and can apply the clinical practice guidelines with high quality of care. So two different professional profiles: advanced, to do research and innovate, and of course basic, with an high level of clinical care.

Giancarlo Pruneri: So this is a very important goal that we have to achieve. We already mentioned in a previous episode the importance of Masters and PhD, we mentioned the fact that there is a the chance to have a PhD programs focusing on new and new figure of a professional that is a scientist and a clinical doctor together. This is absolutely important. You already mentioned that you have been elected as ESMO president. This is for the next to 2027-2028 biennium. So this is a truly important let me congratulate with you because this is a truly important achievement for you, for us and the European oncologists. So firstly, it is very important to me that you know, a guy like you that with this open mind with regard to precision oncology and to the implementation of technology for carrying our patients, has been elected as ESMO president. So my question here for you is how do you foresee oncology in the next ten years, and which role should be played by national and international associations?

Giuseppe Curigliano: Well, you know, I believe oncology in the next years will be a platform for interconnections across disciplines. So in my mission, there was really to generate a scientific society that can be a platform in order to integrate different aspects of cancer care, starting from diagnostic to pathology and of course also to surgery, radiation oncology and medical oncology. In my opinion, per definition, cancer care is multidisciplinary and in order to optimize outcome of our patients, we need a multidisciplinary approach. And now, with the new technologies that are driven by artificial intelligence and by algorithms that eventually can refine diagnostic and also treatment algorithm is very essential to have a governance of all this process. So in my opinion, the future of medical oncology in the next ten years will be much more related to a better knowledge of the biology of the disease, to an interception of cancer before appearance or interception of cancer before recurrence. So what I envision is to start treatment before cancer will develop with the really primary prevention program, or eventually in case patients have cancer to intercept recurrence with new cancer treatment that can delay the metastatic disease.

Giancarlo Pruneri: Giuseppe, thank you very much for being with us on TJ talks. It was a very pleasure for me.

Giuseppe Curigliano: Thank you very much for inviting me and see you soon.

Giancarlo Pruneri: So in this episode, we found out how to craft the new avenues for precision oncology. We have been discussing with Giuseppe Curigliano, an eminent scientist, oncologist, teacher and mentor, and the new elected president for ESMO. TJ talks is available on our website tumorijournal.org and on the best podcast platforms. Follow us on Twitter and LinkedIn to always be updated on cancer research and clinical practice in oncology. I’m your host, Professor Giancarlo Pruneri, editor in chief of Tumori Journal. Thanks for listening.

Giancarlo Pruneri: Food is medicine. This was the title of an editorial published in Nature, and the evidence is growing that targeted dietary interventions can treat, delay, and even prevent some illnesses. Today we are focusing on this topic with Professor Claudio Vernieri. I am Professor Giancarlo Pruneri, editor in chief of Tumori Journal, the peer reviewed oncology journal dedicated to the dissemination of key oncological themes and advancements. Welcome to TJ talks, conversation about oncology by Tumori Journal. Hi Claudio, thanks for being here.

Claudio Vernieri: Hi Giancarlo, thanks for inviting me.

Giancarlo Pruneri: Claudio, let me introduce you. For those who don’t know you yet, you are a breast oncologist working at the National Cancer Institute of Milan and a university professor and the PI of a prospective study on the efficacy of a metabolic intervention added to chemo immunotherapy for patients with triple negative breast cancer. Wow. That’s a lot for someone as young as you. Is there anything you’d like to add?

Claudio Vernieri: Yes, I’m also a group leader at IFOM, where I direct a group of eight scientists, basic and translational scientists who are studying novel approaches to target cancer metabolism. And this is an especially exciting moment because now in the clinic, we are investigating approaches that were studied in the laboratory 10 or 5 years ago, and at the same time, in the lab, we are studying new approaches that will be the focus of clinical trials in the future.

Giancarlo Pruneri: Wow, that’s exciting and I’m truly hoping that your day is lasting more than 24 hours. Claudio, can you explain how you came to hypothesize that a metabolic intervention could help in cancer treatment?

Claudio Vernieri: Yeah. Thank you for your question. So when I got interested in this research field in the cancer metabolism field, about ten years ago, what I did first was to study a lot of literature, trying to understand among several metabolic approaches that were being investigated in several laboratories around the world at the time, which of them could be potentially more feasible and potentially also more effective in cancer patients? And so this process lasted for a couple of years, during which I designed a specific calorie restricted regimen that we started to investigate in cancer patients at the beginning of 2017.

Giancarlo Pruneri: Wow. I mean, so it’s starting from basic science and getting to patients quite quickly. And here we are today with a breakfast-2 to study. And what are the goals of this study and where are we currently?

Claudio Vernieri: So the breakfast-2 study is a phase two randomized, multicenter clinical trial, which is randomized in patients with stage two or stage three triple negative breast cancer to undergo a specific calorie restricted regimen in combination with standard preoperative chemoimmunotherapy. And the primary objective of this study is to investigate whether the addition of this calorie restricted regimen to the standard medical therapy is able to increase the rate of pathologic complete responses when compared to the standard treatment alone. So now we have started recruiting patients about one year ago, and very soon other Italian cancer institutions will adhere and will start enrolling patients in the context of this trial.

Giancarlo Pruneri: So this is very interesting. So it’s I mean a clinical intervention. Are you planning to get, you know, some translational studies in order to answer some biological question?

Claudio Vernieri: Yes, of course, I will be conducting collaborations with you, with your group, several genomic and transcriptomic analysis, both at bulk and single cell levels, with the main aim of understanding what is the impact of the experimental interventions on the intratumoral immune system, and also on systemic and intratumoral metabolism, because we hypothesized, based on results of preclinical experiments, that specific metabolic changes that occur at the tumor level very precociously may predict the response of the tumor to the experimental approach.

Prof Giancarlo Pruneri: So this is very interesting. Let me tell you from an organizational point of view, is that completely an academic study or do you receive funding from companies and industries?

Claudio Vernieri: So this is a very important point, and I’m proud to say that this is a fully independent study. So we received different types of fundings from foundations, organizations but not from pharma companies. And this will allow us to be totally free in the design and in the analysis of the clinical results, but also in the conduction and analysis of translational data. That will be so important to understand the biology that is behind this type of experimental intervention.

Giancarlo Pruneri: Sure, Claudio, it must not be easy for a woman with cancer carrying all the anxiety and legitimate fear to follow a diet. How do you support your patients and what tools do you use to comfort and provide them with precise instructions for following the diet?

Claudio Vernieri: Yeah, this is a very crucial point. I have to say that this is a very peculiar historical moment because cancer patients are more and more interested in investigation and nutritional interventions. Everybody basically is asking, what should I eat? What should I drink during my cancer treatment? And so in general, patients who are proposed this type of experimental intervention accepted very enthusiastically. So what we are doing now to support these patients is to follow them very closely, to monitor them and to this aim we have developed, in collaboration with Arama Precision Oncology, a specific instrument, which is a web app that will allow us to collect on a daily basis information about the side effects, tolerability not only of the diet, but also of the medical treatment, and to provide timely suggestions and recommendations to prevent and to manage these side effects. So I’m pretty optimistic that also on a multisensory base, this trial will be successful on this point.

Giancarlo Pruneri: Yeah, sure. Claudio, this is very interesting. So please explain it a bit more precisely. I mean, so the patients are able to contact the clinicians through this app whenever they have some doubts or are requesting some advice?

Claudio Vernieri: Yes. Patients have the opportunity to use this chat, which is open with the investigators of the breakfast trial, both oncologists and nutritionists, and to ask whatever they want regarding side effects, doubt about their nutritional regimen and so on. So this is an opportunity to have a very close contact with the patient, to improve the participation of the patients and also their compliance, and also to prevent and timely manage side effects that are related either to the medical treatment or to the investigation and nutritional intervention.

Giancarlo Pruneri: And I mean, I guess that they can do that 24 hour per day. So this is meaning that, you know, you have a lot of free time left. And I mean, Claudio, I would like to thank you for being with us on TJ Talks.

Claudio Vernieri: Thank you, Giancarlo, for this invitation. It was a great pleasure to be here today.

Giancarlo Pruneri: And as I wrap up, let’s circle back to Feuerbach idea: we are what we eat. It’s a simple reminder of how crucial our food choices are, not just for the daily health, but also in the fight against serious diseases like cancers. These therapies are all about disrupting cancer cell bioenergy, proving that our battle against cancer can indeed start on our plates. And remember, choosing the right foods is not just about good health, it’s a key part of our fight against cancer. Follow us on Twitter and LinkedIn to always be updated on cancer research and clinical practice in oncology. I am Professor Giancarlo Pruneri, Editor in chief of Tumori Journal. Thanks for listening. TJ Talks is available on our website tumorijournal.org and on the best podcast platforms.

Giancarlo Pruneri: What are the reasons that make really unique the role of pathologists in the model of precision oncology today? and which are the reasons why doctors should be involved in a specialization course in Milan? To find out, I invited Doctor Emanuele Frigo, who is completing his specialization course here in Milan. We will discover his story, follow his path and very importantly, which are the opportunities offered by the specialization course and the PhD course. I am Professor Giancarlo Pruneri, editor in chief of Tumori Journal, the peer reviewed oncology journal dedicated to the dissemination of key oncological themes and advancements. And this is TJ talks: Conversation about Oncology by Tumori Journal. Hi Emanuele, thanks for being here.

Emanuele Frigo: Hi, Giancarlo, thank you for inviting me. I’m really pleased to be here.

Giancarlo Pruneri: Emanuele, would you like to introduce yourself to our listeners?

Emanuele Frigo: Sure. I am Emanuele Frigo, a resident in pathology currently working at fourth and last year of the residency program here at the University of Milan. And I am also, since January 2024, PhD candidate in IFOM in Milan. And I’m currently working on research, preclinical and translational research on tumor metabolism with a focus on melanoma.

Giancarlo Pruneri: Wow. That’s great. But we will talk about a PhD maybe later on. Firstly, Emanuele, could you describe what today does a pathologist involved in precision oncology?

Emanuele Frigo: Sure. Traditionally, pathologists have been at the forefront of clinical diagnosis in tumors, and they had profound knowledge of cancer biology, its clinical settings and also the molecular profile of tumors. So I think that pathologists among many medical specialists are probably the most appropriate professional figure to be a bridge between a morphology, the clinical settings, and the molecular profile of tumors. If we think that the recent advancements in the genetic testing have profoundly modified the traditional classification of tumors, and so also the knowledge that pathologists have also in the technical aspects of the molecular testing, can have a huge impact into the field of precision oncology. Pathologists have different roles in different aspects of the management of the patients in oncology, from the pre-analytical phases to, for example, the management and the proper choice of the tissue samples, cytological samples, both in terms of quality and quantity, in situ techniques, for example fish RNA sequencing and so on, and also they can integrate molecular data into the clinical Oncology Reports. We also participate in the multidisciplinary team and the clinical decisions, among other professional figures, and they can participate in the core aspects of the precision oncology, which are the discovery of the new biomarkers or targets inside the tumors that are exploitable from a therapeutic point of view. So, I think that pathologists are really they cover a really important and crucial role in oncology.

Giancarlo Pruneri: Impressive, Emanuele. So, it’s a kind of balance between the traditional pathology with classification and the new molecular avenues. And in order to do that, you choose the specialization course in pathology at the University of Milan. Can you explain why?

Emanuele Frigo: Yeah, that’s a great question. Um, initially, after my medical training, I wasn’t sure to be a pathologist. Actually, I was unsure whether it was the diagnostic of tumors or the clinical aspects of tumors to be my main topic of interest. So I undertake a residency program in the radiation oncology at a European Institute of Oncology here in Milan. And during that period of one year, I became progressively more interested in the diagnostic aspect of diseases through the participation at many, many multidisciplinary meetings in European Institute of Oncology with pathologists and oncologists across different fields of oncology. So, I decided to undertake the residency program here at the University of Milan in pathology. And thanks to its extensive networks of big hospitals with high quality standards and also a wide range of clinical expertise across many sub specializations in pathology, doing residency pathology residency in Milan offers a huge possibility of professional growth through also the rotation through across all these different big hospitals.

Giancarlo Pruneri: That’s great. And it’s very interesting. I mean, and can you quite schematically, you know, describe us a normal day life in, in the life of a pathologist?

Emanuele Frigo: As a resident, we participate in every aspect of the clinical routine, diagnostic routine in the pathology department of our current rotation. Starting from the first and second year, our activities mainly centered around acquiring basic knowledge into the gross microscopic examination of tissue samples and autopsies, and also basic general histology. From the third year, we dive deeply into the special histology cases and the final year we have also the opportunity to follow research, but clinical and preclinical, like what I’m doing with a PhD at this opportunity the last year. We also have the opportunity to do up to 18 months abroad that can widen our knowledge in, in the field. So, it’s pretty varied activity across the whole four years.

Giancarlo Pruneri: Emanuele, you mentioned earlier that during the specialization course there is also a PhD course that is the physician scientist course. I think that it’s a fantastic opportunity for young doctors and specialization students to get a quite comprehensive approach in education. And in fact, you can work in a cancer center like the Fondazione Istituto Nazionale dei Tumori, Milano, and in a research center like IFOM, in order to get, you know, skills either in oncology and in tumor classification, but also in the biological basis of disease with a very translational approach. Can you just underline quite quickly what are you doing at the moment?

Emanuele Frigo: Thank you. Yeah, I really think that, as you mentioned, this is a great opportunity for us residents to reach clinical and preclinical research through a PhD and a clinical aspect of our activity as a residence in the Istituto Nazionale dei Tumori. To just give you an insight of what I’m doing during my PhD course, I work on two more metabolism, and in particular, I’m trying to dissect the mechanistic impact of specific metabolic pathways in affecting the response to immunotherapy in melanoma patients. And I’m trying to do this through the development of an in vitro and ex vivo models that are able to explore deeply the heterogeneity of the tumor and also its microenvironment.

And to do this, at the beginning, it was very demanding, but also a little bit of chaos, I would say, because I had to go back to the basics, and I was the start of my fourth year as a resident in pathology, but really I had no knowledge about how to manage an Eppendorf, for example, or how to also prepare media, for example, for the cells. So, I had to discover a lot of new things to learn, a lot of new things day and night, basically. But I also had the opportunity to meet very, very welcoming colleagues there in IFOM that are very open to help me through this journey.

I am three and a half months into my PhD course, and I’m starting now to realize that by doing this, it really gives an open up new opportunities from a professional point of view, but also it offers me to be able to bridge the world of pathology and the world of clinical research into one thing. That’s one of the main purposes of doing this.

When you, Giancarlo, proposed us residents to participate in this PhD program, I was in at the University of Leuven in Belgium, and I was doing a fellowship, working on clinical aspects of melanocytic tumors and melanoma. And I had also the opportunity to work on clinical research on that topic that brought me to present work on at the National Belgian Congress in Brussels and the Anglo-French meeting in Paris. And so, by doing this PhD, I really, took the opportunity to work on my main field of interest from the clinical point of view at Instituto Nacional de Tumori, where I work on the classification of tumors and in the diagnosis of them, and from the research point of view at IFOM. And this is really exciting, and I can’t wait to progress on this.

Giancarlo Pruneri: Exciting indeed. Emanuele, and thanks for being with us on TJ talks.

Emanuele Frigo: Thank you very much, Giancarlo.

Giancarlo Pruneri: [00:09:59] In this episode we found out how the role of pathologist is central in precision oncology. The pathology training is indeed rich and multifaceted. The training is focusing on classifying tumors and pinpointing biomarkers for treating patients with tailored therapies, mainly using molecular biology techniques. And yeah, we’ve learned about these cool new PhD program which is shaping new physician scientists. These professionals are going to be a bridge between traditional clinical care, patient treatment and research. And it just seems like this is the best way to take care of our patients. TJ talks is available on our website and on the best podcast platforms. Please follow us on Twitter and LinkedIn to keep updated on cancer research and clinical practice in oncology. I’m Professor Giancarlo Pruneri, editor in chief for Tumori Journal. Thanks for listening.