Podcast "Let's Talk Cancer" – The future of oncology: new technologies and tailored treatment

The past few decades have witnessed significant strides in how cancer is detected, diagnosed and treated, leading to a noticeable decrease in mortality rates in many countries.

These improvements are largely due to new discoveries about why and how cancer develops, generating new ways of treating cancer to help people live longer, healthier lives.

From immunotherapy and AI to cancer vaccines – Cary Adams, CEO of UICC speaks with Dr Laszlo Radvanyi, President and Scientific Director of the Ontario Institute for Cancer Research, an internationally renowned research institute located in Toronto, Canada, who is at the forefront of some of the most ground-breaking work in cancer research.

See podcast transcript below

 

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Podcast transcript

Cary Adams: Welcome to Let’s Talk Cancer. I’m Cary Adams and I am the CEO of the Union for International Cancer Control. Globally, cancer remains a major health challenge, with nearly 10 million related deaths reported in 2022. The past few decades have witnessed significant strides in how cancer is detected, diagnosed, and treated, leading to a noticeable decrease in mortality rates in many countries. These improvements are largely attributed to new discoveries about why and how cancer develops that have generated new ways of treating cancer to help people live longer, healthier lives. Doctor Dr Laszlo Radvanyi is president and scientific director of the Ontario Institute for Cancer Research. He is at the forefront of some of the most groundbreaking work in cancer research. He joins us for this episode of Let’s Talk Cancer to talk about innovative cancer treatments such as immunotherapy and precision medicine, where treatment is tailored to a person’s unique genetics. Laszlo, thank you very much for joining us today. It’s a pleasure to talk to you.

Dr Laszlo Radvanyi: Great. It’s nice to be with you, Cary, and look forward to the discussion.

Cary Adams: Well, let’s start off with the incredible advances that we’ve seen in cancer research in the past decade. I mean, what do you think has generated this real big surge forward in understanding cancer and the opportunity to treat cancer?

Dr Laszlo Radvanyi: Well, I mean, first and foremost, it’s just the sheer increase in the volume of our knowledge and how science has moved forward over the last several decades. I mean, we began 30 years ago, you know, not even knowing what are the genes that are driving cancer. And then we’ve identified those driver genes against cancer. Then we’ve identified genes that suppress cancer in our body and, you know, found out how they’re shut off. And then they made. And then we’ve made tremendous strides in understanding our own immune system, which we really didn’t understand 30, 40 years ago, our so-called T cells and how they fight off disease and infection and then, miraculously, and how they can fight cancer.

Cary Adams: What about technological advances?

Dr Laszlo Radvanyi: We’ve had huge technological advances. You know, when I was a student working in the lab, compared to my students and my trainees in the lab, I mean, the amount of instrumentation and efficiency in the lab to do things and to discover things. I mean, we’re moving at such a rapid pace right now in the area of genomics by understanding, you know, how to sequence our genomes, and what our cells produce. So, I mean, we can now do it within a day or two, whereas several decades ago, it took over a year or more. And, and the costs have tremendously gone down. So we can generate more data, at much less cost with better technologies. We understand the inner workings of the cells and cancer and also communication and international collaboration, of teams of scientists working together not only within countries but across countries. And sharing of data has increased. And we have tremendous data informatics tools to share data and to drive, you know, big data systems to really then churn out this data, understand cancer better.

Cary Adams: It’s certainly an exciting time. And one of those exciting developments is precision medicine, of course, and that encompasses early detection, diagnosis and treatment involving all sorts of new technologies and therapies. So can you explain maybe in a few words, what precision medicine is and how it works? Because a lot of people know the words, but they don’t really understand what it means.

Dr Laszlo Radvanyi: Well, first of all, let me be a little bit controversial and I and admit to everybody or say I don’t like the term precision medicine. Because the term precision AI actually comes from statistics, it means that you’re able to reproduce things and generate the same data, using the same method, over and over again with very little variability. That’s what really precision is. We’re really talking about accurate personalized medicine. And I like the word accurate oncology or accurate medicine because it’s really finding the best medicine for the right patient at the right time, at the right dose, in order to be able to generate the maximum efficacy for what you’re trying to use that medicine or that therapy for. And at the same time, understanding the patient’s unique needs in terms of quality of life, by reducing toxicity, for example, one of the hallmarks of precision medicine or accurate medicine is the use of biomarkers. Every patient’s cancer is unique. We need to understand each patient’s cancers from a deep molecular standpoint. And now we have all these amazing tools to actually sequence a patient’s tumour, to understand what’s going on in the blood, to do imaging, etc., and other so-called real world data from the patient. And we can then combine all that data and then and then using the tools at hand in the medicines at hand, we can then, develop or conceptualize the best sort of individualized or personalized accurate, medicine, for that patient. Each patient is an N of one. Each patient is unique and we need to treat that patient accordingly.

Cary Adams: It sounds like, from what you’ve said, that it relies heavily on computers and data banks, and intensity of understanding rapidly with the brain can’t cope with it. So you need to have the technology to sort all that out and give you direction. What role is AI playing in that? Another subject matter which is discussed a lot across the cancer community.

Dr Laszlo Radvanyi: Yes, AI is a buzzword. Everybody’s using it. A lot of people don’t understand it. A lot of people are afraid of it. Let me start off by saying AI has huge potential implications for revolutionize how we treat cancer. And not only that, but how we reduce cancer disparities in terms of access to therapy and doing the best therapies at the right times for patients all across the world, especially in underserved communities within our own countries, but also in in underdeveloped and developing countries across the world. By generating big data from multiple sources, through research, through clinical data, through imaging, etc. as we combine more and more of those data sets, our brains can, you know, fathom mining all that. So what the magic or the amazing thing about AI is that we can churn through these data, find those comparisons, find those predictive things we need to do, to find better therapies, even find new targets for cancer in the reams and reams of data, biology data, clinical data, real world data that we never thought that we can find. It’s also going to revolutionize cancer diagnostics and cancer detection, because we still have trouble finding cancers early, even breast cancer using, for example, mammography. There’s a lot of false negatives. There’s error that humans have in looking at these things. And AI algorithms also promise to sort of, you know, solve some of the errors that we have, in our judgment, and help us make better judgments in terms of diagnostic detection as well as better therapeutic choices for our patients. I think we’re seeing a big revolution, especially if we use AI wisely, if we use AI ethically, and if we make AI systems, fairly and ethically available across the world to everybody, not just the few.

Cary Adams: Laszlo, do you feel that the oncology community share your optimism about this, or is there a fear within the oncology community about their jobs, their roles, etc., etc.? Do they do you feel that there is a general optimism?

Dr Laszlo Radvanyi: I think there is. But at the same time it’s tempered with a sense of fear. Pathologists, for example. Now there are new AI tools. For example, just by taking a simple stain slide of a tumour that, you know, pathologists used to look at under the microscope and make all sorts of diagnostic decisions as to what type of cancer it is, what stage, etc.. Now we have imaging tools that simply scan that slide, and then AI algorithms that can actually not only tell you what type of cancer it is, what stage it is, but even now molecularly classify that cancer and be able to then glean treatment decisions and other clinical management decisions based on that.

Cary Adams: So what can be done to reduce fears?

Dr Laszlo Radvanyi: I think what the problem is with AI is that it’s a misunderstanding. I think there’s a lack of. Education. It’s really important for the data science community and all these amazing data scientists that are generating these tools, and the AI pioneers to really educate the public and educate clinicians about what AI is, the power of the of AI, and how to use it responsibly, such that you’re not eliminating or putting at risk the role of the human element. And there has to be a human element in AI, because ultimately we’re the ones that dispense the therapy, were the ones that make the decision of what we’re going to do with the patient, not the computer. So we’re the last as humans, last arbiter in anything that’s churned out through an AI algorithm. And so I think we need to approach AI and clinicians and clinical management as a tool, as a really powerful tool to help us make those decisions. And we need to educate our clinicians to be comfortable with it and understand what AI can and can’t do. And I think that’s probably one of the problems right now in our society overall, that not many people understand it. So we’re afraid of what we don’t understand. But at the same time, we need to be careful and again develop those ethical rules of developing AI. So then, you know, we don’t, you know, eliminate the human element. I am concerned though about that. Because human intuition is still, I would say, a superior thing.

Cary Adams: I think there’s a sense of fear and worry, but at the same time, optimism about the potential has to, at the end of the day, save more lives. And ultimately, that’s what the oncologists are trained to do. They want to save lives. So let’s see how it goes. But I think in the next ten years, there’ll be some dramatic changes in the way that we can detect and treat cancers. And let’s talk about immunotherapies. Um, part of that portfolio of new approaches to accurate, personalized treatment, as you described it earlier. Um, a lot of people hear the word again, but they don’t really understand what it is. Could you explain your perspective, what immunotherapy is?

Dr Laszlo Radvanyi: Immunotherapy and the our immune system is an immense and powerful weapon against cancer. But at the same time it is a two edged sword. Our immune system can actually, under certain conditions, can actually be a driver of cancer, sort of cooperating with those mutations that occur in our cells that sort of derange our cancer cells. I think we need to understand both sides of the coin, why the immune system can sometimes drive cancer, but why, you know, the excitement, for example, why the immune system can actually help eradicate cancer. Essentially, our immune system is really our response to the outside world, right? From our skin to what’s happening inside our body to fight infection and other, you know, viruses and other pathogens. It’s really why we can survive as a species. How was the.

Cary Adams: Study of immunotherapy evolved over time?

Dr Laszlo Radvanyi: Over the last several decades, there’s been tremendous advances in understanding not only the basic mechanisms of the immune system and how they fight infection, and then understanding how that understanding of the immune system at a deep level now, and the molecules and the pathways and that regulate all our different immune cells, how they then can be, interpreted and how they can be applied in context of cancer because of our increased understanding of the immune system and how it’s involved in cancer eradication, but also cancer driving cancer, I think now it’s widely accepted as one of the most amazing, pioneering revolutions in cancer therapy. Um, and also in the last several decades, we’ve understood, sort of our brakes on the immune systems. I mentioned that, for example, our immune system is really also evolved not only to fight infection, but also evolve the mechanisms to stop ourselves from killing ourselves through our immune system, by preventing our immune system from attacking our own cells. Well, unfortunately, cancers usurp that process. They trick us by turning on those processes that tell our immune system, hey, I’m a normal guy. I’m a normal girl. Don’t touch me. You know? And then, and then the immune system says, oh, okay. And then, of course, the tumour isn’t fought off and the tumour continues growing. And I think one of the tremendous revolutions, I think our understanding of the immune system is how these sort of so-called self-tolerance mechanisms are usurped by cancer, how they turn off our immune system. And then what are the molecules and pathways that turn this on? And then we can actually develop therapies. And we’ve developed what are called immunotherapies. Now we’re able to develop these types of drugs that are able to prevent our tumours from telling our immune system, hey, you know, we’re normal. And then the immune system. Then says, hey, we’re not normal. I’m going to attack you and kill the cancer.

Cary Adams: And will this have a major impact on cancer control?

Dr Laszlo Radvanyi: It’s an amazing, amazing, pioneering advance, and we’ll be seeing more and more of those as time goes on. Another pioneering advance is the area of cell therapy. We understand how the cells of our immune system fight off infection, and how we can then harness ourselves through what are called cell therapies, to, to fight off cancer, where we can take cells out of our body, reprogram them to fight cancer, and then actually put them back in our bodies and fight cancer. One of the most powerful, therapies, against cancer.

Cary Adams: Some cancer types are more readily open to immunotherapy than others. Can you explain why that is?

Dr Laszlo Radvanyi: Our immune system recognizes things that are foreign, and we’ve known that for a while. That’s why our immune system reacts against pathogens like viruses, bacteria, fungi, etc.. But we realized that cancers, because they’re driven by mutations and alterations in our genes that then produce altered proteins, abnormal proteins that don’t function normally, either they don’t suppress the cancer or they drive the cancer. And that these gives we found that these gives rise to novel what are called antigens or things on, on, on the surface of the cancer cell that are recognized as foreign by our immune system, just like viruses and bacteria. And so the more foreignness or mutations the tumour has and decorates itself with these sort of foreign things that the immune system sees, hey, this is not myself. This is not, you know, our own body’s stuff. The more the immune system will recognize it as foreign and then get activated and try to kill, you know, whatever it sees as foreign. So the more so, I guess what that translates to is that the more mutated a cancer is, the more it’s seen by the immune system. And then the better that immune the immune responses. And so tumours such as cancer, such as melanoma, for example, that are induced by UV light, for example, that has a tremendous amount of mutations compared to, let’s say, an oestrogen receptor positive breast cancer or a prostate cancer, for example, are generally more so-called immunogenic to the immune system.

Dr Laszlo Radvanyi: And that you can use these modern immunotherapies such as checkpoint blockade and other therapies such as cancer vaccines to fight these cancers, because intrinsically, before you even treat the patient, our immune system already has a better response against these tumours, and we can accentuate that response better with tumours that are less mutated, we have to do some tricks to try to coax the immune response into seeing that cancer as more foreign, because it’s less mutated. And although many cancers that are less mutated, are less immunogenic, there are still mutations. And so it’s a matter of just developing more finesse technologies for us to find those mutations and then program our immune system to target those mutations. It is possible we just have to be smarter and develop better technologies for those less mutated tumours, for immune system to fight it versus the more mutated tumours. But we’re getting there, and one day we will be there. We’ll be able to, like, treat more or less all cancers equally by doing this, with our immune systems.

Cary Adams: You mentioned cancer vaccines, and that’s been in the press recently in the UK about the potential for using the mirror technology for cancer vaccines, and what hopes do you have for that?

Dr Laszlo Radvanyi: Well, huge, huge hopes. Um, I think vaccination is one of the huge, hallmarks and revolutions, in human health. It saved the lives of millions and millions of people from infectious diseases for centuries. You know, there was a time when there was this big hype about cancer vaccines in the in the 1990s, when immunotherapy and understanding the immune system against cancer. That knowledge started taking off. And we identified what are called tumour antigens, these foreign things on tumours that are recognized, the immune system. And then a lot of people, you know, went into the tumour vaccine field and there was a lot of research and clinical trials, and many of them failed. Most of them just failed. And there was a sort of a lull, kind of, system, this, this sort of valley of disillusionment, so to speak, in cancer vaccines, where people started saying, well, it’s not going to work. And but then again, because we didn’t understand these other mechanisms of why the cancers are able to shut off the immune system, why some cancers are more mutated than others, and how to and that the cancers, many tumours are recognized by the immune system because of these mutations. And these tumour specific mutations are being recognized by the immune system. Now, fast forward into the 21st century. We’re now seeing a huge revolution in cancer vaccines not only to treat already established cancer. By identifying what are those antigens that we can target those mutations, and then we can rapidly make vaccines and then vaccinate patients in a personalised way.

Dr Laszlo Radvanyi: I think this is what the huge revolution is. Using mRNA technology, we can sequence a person’s tumour, understand what each individual’s, sort of repertoire of mutations are, and then quickly make an mRNA, an mRNA vaccine that targets those mutations, and then and then vaccinate the patient to sort of boost the immune response. So those are called therapeutic vaccines. We treat patients with already existing cancer. Now another exciting, really exciting area now is because we understand that many cancers are driven by so-called, you know, sort of, foundational driver mutations, many patients, for example, that have hereditary cancer syndromes that have deficiencies in DNA repair, they have mutations. We can identify what those mutations are that actually that will drive the cancer before the cancer will actually even evolve. What that brings up is a really exciting possibility, which is now already being tested to actually make so-called preventative cancer vaccines, for example, using mRNA, where we can encode these drivers that will drive the cancer and then program and educate the immune system to respond against that. So as soon as the cancer cell starts to go crazy, a small tumour, our immune system then can recognize that right away before that cancer takes off and eradicate that cancer. So cancer vaccines not only have the potential to prevent cancer, but also to treat already diagnosed cancer and prevent recurrence.

Cary Adams: Well, having cancer vaccines, which can prevent cancer at a very, very early stage by educating the immune system, sounds like a great way of addressing some of the global challenges we have with regard to, you know, cancer in low and middle income countries. Um, you said at the beginning of this, this discussion that, you know, this is AI technology. Data is opening up the opportunity to address cancer globally. We know that majority of deaths occur in low middle income countries. Our cancer vaccines that prevent cancer, one of the technologies you think could really make a difference in closing that equity gap around the world?

Dr Laszlo Radvanyi: Possibly, yes. If we if the well-to-do countries and the pharmaceutical companies, etc., really want to sort of level the playing field. We know that vaccines, for example, against infectious diseases like, like for example, smallpox, etc., polio, are relatively cheap. I mean, these don’t have to be expensive. And so we need to be careful about, you know, price gouging and sort of the, you know, some of the issues that have arisen with the cost of cancer, of therapeutics. Now, with that said, depending on the type of cancer vaccines or preventative vaccines you’re dealing with and how difficult they are to manufacture and how expensive, of course, you know, there’s a cost issue there, but I think, vaccines could add AI and data science tools, for better management and, and also, other tools such as early detection by. Blood samples through what are called liquid biopsies and cheaper, genomic sequencing tools on those blood samples. I think all of these can level the playing field across the world. So I think, yes, vaccines if we do it right. But again, one of the major problems with using vaccines to prevent cancer is, you know, we still know relatively little about the genomics and about how cancers are different in different demographics than, you know, so-called the white Western American population that has dominated our international genomic databases. I think right now we need to get better at inclusivity and diversity, in these large genomic data sets, in terms of understanding cancers, in all demographics, in all cultures, in all races, cancers are unique in different people. But at the same time, there are unique differences between different, racial and ethnic groups, in just the genomics of, of those people. And then that is reflected in their cancers. So we need to get a better, more democratized understanding of cancer at its most basic levels by understanding genomes of people all across the world. Once we know that, we can understand better those drivers and susceptibility factors. Once we do that, then we can actually then more rationally develop vaccines to perhaps prevent cancer while.

Cary Adams: We wait for those new developments, is there something we can already do?

Dr Laszlo Radvanyi: One of the major things we can already do to prevent cancer is by, for example, all across the world in embracing the human papillomavirus vaccines and other antiviral vaccines that we know can cause cancer. HPV vaccination has revolutionized the prevention of cervical cancer and in other cancers driven by that virus, such as head and neck cancer. So we can already make tremendous inroads in the developing and underdeveloped world by ethically and equitably providing these types of vaccines. And then as technology takes off and we understand cancer is better in different racial groups across the world and what drives them, then I think we can be in a situation where we can actually start developing preventative cancer vaccines for people across the world.

Cary Adams: I certainly agree with you that part of the challenge is actually to get our own house in order, in terms of collaboration and sharing and wanting to focus our attention on addressing the inequity gap globally. So I would really appreciate hearing any other views you have on that. Apart from the technology, what else needs to be put in place?

Dr Laszlo Radvanyi: Yeah. First of all, I’d like to laud the UIC and its work. Um, it’s an amazing organization. I’m proud to be part of it and help the UIC in any way I can, because I think, you know, everyone in the world has a right to health care. I think, UIC and its partners, can be very instrumental in really breaking down some of these disparity barriers because I think these are going to be growing. Unfortunately, as we develop more and more intricate technology, targeted therapies against cancer, requiring a lot of upfront workup of the patient through, let’s say, genomic sequencing and things like that, we have to be careful that we’re not going to enter a world where there’s going to be haves and have nots, where the have nots are not going to have access to these types of technologies, and then we’re not going to be able to then deploy the most intricate and the best personalised therapies, and they’re going to lose out. So we need to really get together at internationally to really, you know, empower access, to, to these data science tools and to these other technologies. And I think we are going to be seeing some positive things, for example, genomic sequencing, for example, which is still very expensive. There are now cheaper, sequencing technologies that are coming up that can be deployed in rural areas and other underserved areas that are cheaper. There’s a new technology, for example, called long read sequencing, which can use these little, small little cassettes and can take a person’s blood sample, isolate the DNA or the RNA and can sequence them very rapidly and very cheaply to get diagnostic answers that can help, you know, for example, decide what type of therapy we need clinicians to work together.

Dr Laszlo Radvanyi: I think one of the great opportunities is to have international clinician teams, or what are called a twinning program, where clinicians in, first world countries can partner up with clinicians in developing countries such as Africa and Asia, etc. and then could have, tumour boards or virtual tumour boards where they can discuss patient cases together. The clinicians can help each other out in providing, better decision making and each providing their expertise. So, so these international exchanges between clinicians, international tumour boards, AI algorithms that can be provided, to developing countries, to, let’s say, to better develop radiation therapy regimens, for example, and other, care regimens, I think is a huge, opportunity countries have to get together and have an international declaration against cancer that we’re going to work together and reach certain milestones which ensure equitability and fairness for developing countries, especially when these new, really intricate genomic based technologies and, more intricate and more highly advanced cancer care comes in, I think, just like we have the climate change declarations and meetings, that I think we should have the same international cooperation.

Cary Adams: That seems like a fine, call to action to end our discussion. Laszlo, I agree, I think we have, component parts of that, but we don’t have really member state commitment despite World Health Assembly resolutions, NCD commitments, cervical cancer elimination, etc. We still were far away from having the same that they have in climate change.

Dr Laszlo Radvanyi: Cancer is the biggest killer. And as our population ages, it’s going to be more and more. But it really behoves us, as wealthier countries, to do it because it’s a huge economic burden and it’s going to be a huge problem to sustaining economic stability if we don’t fight the cancer problem across the world, especially in every country, including developing countries, to then bring up their economies, because everything is interconnected. And I think, again, data sharing is another area that OICR has been working on internationally. I think we’re living in a time where people are becoming protectionist. You see it across the world. And I think this is very counterproductive because we need to share data internationally, to really help each other out.

Cary Adams: Well, thank you very much for giving us an overview of some of the advances that we’re seeing in, specifically accurate, personalized treatments and diagnostics. I’ve learned a new phrase, and I will use that in the future, but also, sharing your optimism about what we could do with this and how the real challenge in the longer term is not necessarily the advances we’re seeing in innovative ways to diagnose and treat, but how we can actually share that around the world more broadly. So I really appreciate your thoughts and thank you very much indeed.

Dr Laszlo Radvanyi: Thank you, Cary, it’s been a pleasure.

Cary Adams: If you’re interested in cancer research, why not listen to episode 26 on Oncology in Orbit, Cancer Research in Zero Gravity, and episode 24 on the history of cancer control. Also, check out the web page of World Cancer Research Day at World Cancer Research Day.com. Cancer researchers are strong feature at UICC’s upcoming World Cancer Congress in Geneva, with the presentation of hundreds of abstracts as well as sessions on innovations in prevention and treatment. And I we do hope you’ll join us this September in Geneva.