Podcast

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.