— Could you please tell me about yourself, Ilya. Where you were born, what schools you went to, and how you became an oncologist?
— I'm from Belarus, born in Mogilev. I completed my secondary schooling there before enrolling in the School of Science at Sechenov University in Moscow. This was a unique school back then, where every student received almost individual attention. We studied in small groups of five, and were taught like the future of science depended on us. I am forever grateful to Sechenov University for putting me on this path. That school was a unique project in every sense. Unfortunately it no longer exists, but I'm hopeful that it will be revived one day. I completed my degree and went to grad school to do cancer research at the Blokhin Center of Oncology. Around the same time, the autonomous non-profit The Kidney Cancer Research Bureau was established. This was Russia's first non-government non-profit research organization, and it's been around for 15 years now. We do all kinds of different research projects at the Bureau, from strictly in-vitro, such as when we look for some cell receptor, to purely clinical, like studying the effectiveness of immunotherapy on patients.

— You're a member of many international scientific bodies and associations. Was it your published works or personal contacts that got you membership?
— I owe my standing in the international scientific community solely to my endeavors in science. I have had some important works published. The Kidney Cancer Association was quick to acclaim my work following our 2007 study where we profiled the role of fibroblast growth factor receptors in tumor progression. I was asked to make a report, and that's how I joined their network. This work is my priority. It's been the keynote of my life's work. It's come a long way since that receptor's role was discovered in kidney cancer. Now we are working to develop drugs for curing it.

— Let's talk cancer. What causes it? How does it occur? Some theories claim environmental factors are to blame, others point the finger at viral impacts, and others still believe that tumors are something like hotbeds of evolution. Does a practicing oncologist even care about the causes of cancer?
— That's a great question! I wish I had a one-size-fits-all answer for it. All these theories you mentioned, they all do exist. The viral theory has been proven conclusively. We know for sure that cervical cancer is caused by the human papilloma virus (HPV). The obvious method of avoiding it is to vaccinate girls and now boys as well. The HPV vaccines available now include single-dose options. Liver cancer is also caused by a virus, the hepatitis virus. The causal relations are indirect here: the virus will invade the liver cells, hepatocytes, triggering an immune response. In this case, the virus does not cause the cell to mutate, it just sets the cell up to be targeted by the immune response.
Environmental impact is definitely the leading factor in some types of cancer. Smoking, the bane of the twentieth century, is known to be a factor in lung cancer. In this case, etiology is of the essence and will be considered during treatment. If a lung cancer patient continues to smoke, the risk is higher of the tumor taking a turn for the worse, and this is something the oncologist must heed. For patients with esophageal cancer, alcohol intake impairs the patient's survival prospects. Here, too, the oncologist may suggest corrective action to mitigate the tumor growth factors.

— One of your most frequently cited works — published in 2014 in Lancet Oncology — discusses the increasing incidence of cancer in China, India, and Russia. At that time, it was double the rates of the US and UK. What was behind those high cancer rates? Has the situation changed in the intervening 7 years?
— One must keep in mind that it takes time to prepare a research, which means the data we used had been collected earlier.
The epidemiological situation was very different then in the US and Russia. But now, it would be fair to say that all trends are very similar in the US and Russia. The Cancer Research Bureau has performed its own prognostic study on cancer incidence and mortality rates in 2035. We worked with the statistician who had done an identical prognostic study in the US, her name is Lola Rahib. She is well-known in professional circles and had done a similar study for the US National Cancer Institute. That's how we found out that the trends are now identical. Russia has caught up in terms of economic disincentives for smoking. Smoking rates have declined, and this has proved sufficient for the top 5 most common tumors to become almost the same in the US and Russia.

— What about China and India?
— We haven't been watching China and India during these years. Let's just say, things are a little more complicated with statistics over there. And there are some country-specific nuances. The most common type of cancer in Asia is gastric cancer. In India, it's tumors of the head and neck. This is different from Russia and its Caucasian patient cohort.

— But let's get back to Russia. Are our trends all positive, then?
— They're mixed. The good news is that fewer people smoke. The bad news for Russia is that the incidence of all types of cancer is going to increase. It is predicted to increase 13% in the next 15 years. This has to do with population aging and growth. There are more people, and they are getting older. Those cell mutations we have mentioned before, they occur more frequently in older people, and they increase the probability of cancerous growth. But on a positive note, the mortality rate is expected to drop 20% 15 years from now. The outcome we're looking at is that there will be more cancer patients, but fewer will be dying. Obviously, this is only a prediction. Different factors might interfere, but the trend is positive overall.

— Do you reckon the mortality rate will drop thanks to advanced treatment methods? Immunotherapy, targeted therapy, checkpoint inhibitor therapy are all popular terms now. Can you please explain these methods?
— These are different forms of medicinal treatment. There are several treatment options in oncology. Chemotherapy, which has been around longer, does not target the tumor exclusively. We attack the tumor with a toxic agent, but it's also toxic to the surrounding tissues, as far as it can reach. In targeted therapy, the blocker is delivered to the specific receptor responsible for tumor growth. Immunotherapy targets our healthy immune system rather than the tumor itself. In cancer patients, the immune system exhibits diminished activity through the action of a range of suppressant factors. Immunotherapy reinvigorates the immune system and directs its efforts against cancer cells. Checkpoint inhibitors are a new brand of immunotherapy. Checkpoint inhibitors is the umbrella term of a family of medical products. They guide the immune system toward identifying specific antigens on the tumor cell and then destroying this cell.

— I think we should backtrack a bit here. What role does the immune system play in cancer progression?
— This is an important question. We all possess natural immunity that fights cancerous substances. Every person develops a million cancer cells during their lifetime. But we don't all develop cancer because our immune system fights them off. In cancer patients, the immune system cannot cope with the issue on its own, it has to be helped by immunotherapy.

— To what extent is this part of clinical practice now? When Tasuku Honjo and James Allison won the Nobel Prize for checkpoint inhibitor therapy in 2018, three or four drugs were mentioned.
— I have a personal story to tell to that end. I remember when Allison presented his findings at the American Association for Cancer Research Meetings in 2007 or 2008. It was a massive hall filled with five thousand people, and everyone rose to applaud the presenter. We were clearly witnessing a revolutionary breakthrough.
We've come a long way since. Lots of new checkpoint inhibitors have been developed, each inhibiting different checkpoints or more specific aspects of the same checkpoint. If we take a look at all monoclonal antibodies known in medicine, the cancer antibodies, namely, checkpoint inhibitors, rank second and third by frequency of occurrence. Thirteen new indications appeared for the top two inhibitors in 2021 alone. What does 13 indications mean? It means that we are potentially equipped to treat 13 new variants of tumors. The only treatment available for gastric cancer used to be chemotherapy. Now we have a registered checkpoint inhibitor for it.
It is important to note that, unlike the earlier generations of immunotherapy, checkpoints could theoretically be applied in the treatment of all existing tumors, with varying success. Now, immunotherapy is deemed to have proved successful in treating lung cancer, melanoma, and kidney cancer. Gastrointestinal tumors used to be viewed as more difficult to cure than other cancers. Now they are no longer incurable, not something immunotherapy cannot fix. These are cancers of the stomach, the esophagus, and the colon. Hormonal tumors, such as breast and prostate cancer, have always been extra resistant to immunotherapy. Today, some forms of hormonal cancer, like triple negative breast cancer, have been found to be responsive to immunotherapy. Depending on the indication, all or most tumors are now responsive to immunotherapy. The future, from my perspective, looks bright in this respect.

— What about other approaches? Not so long ago, there were high expectations for angiogenesis inhibitors and hormone therapy.
— Indeed, the first major breakthrough in recent decades had to do with angiogenesis. This is targeted therapy that influences the vascular growth factor or the receptors or proteins in the tumor cell. We prevent blood vessels from growing into the tumor, thereby denying it the nutrients it needs to survive and grow further. We were able to increase survival rates for kidney cancer patients using targeted therapy with angiogenesis inhibitors. At the time when I started working in this field, patients with metastatic kidney cancer had 4-6 months to live, now they have years. We're seeing a 5-year effectiveness rate with these drugs. But we've advanced further, developing combinations of targeted therapy and immunotherapy. It makes sense to combine this highly effective drug with a checkpoint inhibitor. So where are we now? Take kidney cancer, for example. The therapy success rate has improved to 70%. This means that in 70% of patients, the tumor will shrink. We couldn't even get a 10% figure before. And we owe this to the targeted therapy and immunotherapy combo.

— There has been some pessimism about targeted therapy due to the fact that tumors tend to mutate, so the target may some day simply disappear. Is that correct?
— Yes, such a problem does exist. As I've mentioned before, the tumor cell never stops changing. New mutations emerge, and some of them may render the cell unresponsive to targeted therapy drugs. But progress never stops either. Work begins immediately on new classes of targeted therapy drugs that are effective in the treatment of those new mutations. Lung cancer is a good case in point. Some time ago, we only knew about two major EGFR gene mutations in lung cancer cells. And so we came up with our first-generation drugs, the EGFR inhibitors. When the tumor cell started producing the T790M resistance mutation, we promptly formulated a third-class drug that suppresses the said mutation. Now we have these, what we call lines of therapy: the 1st, 2nd, and 3rd. We can indicate them in succession, or we can indicate the appropriate one right from the start. This is the evolution of targeted therapy.

— Would it be an accurate assessment if I said that biotherapy, as opposed to chemotherapy, has been a game-changer in oncology?
— Yes, for the majority of tumors, that would be a fair assessment. But there are tumors we cannot beat, not yet. One is pancreatic cancer. According to our prognosis, the incidence of pancreatic cancer and the associated mortality rates are set to increase, unlike lung cancer, for instance. Pancreatic cancer statistics are grim. The survival rate of five years is only 10% for pancreatic cancer patients, even if you catch the tumor at an early stage. Which is to say, only 10% of patients will live for another 5 years or more, compared to 74% for kidney cancer patients. That's a big difference. But new treatment solutions are being explored for pancreatic cancer as well, including next-generation targeted therapies. Some patients get this so-called BRCA gene mutation, which was previously found in patients with ovarian, breast, and prostate cancers. The blockers used for those other cancers are currently under research and have been approved for use in pancreatic cancer treatment. It is worth noting that pancreatic cancer patients themselves contribute a lot toward the advancement of therapy. For instance, the PanCAN association of patients supports pancreatic cancer research. Before this action network was established, the world had seen just one study on pancreatic cancer. Now there are some 100 studies in progress. Patients themselves can be the driving force behind this progress.

— Are there any contraindications for using the cutting-edge methods? In surgery, I guess contraindications don't matter as long as the surgeon can reach the spot with their scalpel, but what about immunotherapy?
— Yes, there are definitely some contraindications. But only few patients are unable to receive these therapies. For immunotherapy, contraindications include autoimmune conditions, when the patient's immune system is already highly active. Other contraindications may include severe allergies, Crohn's disease, and multiple sclerosis. If we apply immunotherapy in those cases, we run the risk of harming the patient more than we help cure the tumor, for immunotherapy would in this case stimulate an already hyperactive immune system.
With targeted therapy that impacts angiogenesis, its adverse side effects may include hypertension and increased blood pressure, because it affects the blood vessels.
As a consequence of that, we cannot treat hypertensive patients who already have high blood pressure. But we can offer these patients personalized treatment by customizing their medication doses. For instance, now it's okay to use immunotherapy on patients with psoriasis, which is an autoimmune disease. Immunotherapy can be applied while keeping psoriasis under control.

— How would you rank Russia's progress in developing innovative cancer drugs on a scale of 1 to 10?
— That's an interesting question. I haven't looked into the data, but off the top of my head, I'd say it's 2 out of 10.

— Well, at least it's not a 1.
— We have very few such drugs, and most of them are still under development. Not that there's anything wrong with drugs being in development before they go to the market. It all started not so long ago, when Skolkovo was set up and, with it, came what I think is a unique system to start up businesses, initiate research, and develop new drugs. It's just there hasn't been enough time. It takes at least 10 years to develop a single drug formula, including time for research. We're still halfway through the process. But some of these drugs are already on their way to the market.  The first Russian targeted drug of the kind that we discussed has now entered clinical trials, which means it has proved effective in preclinical trials. This is a Russian immunotherapy solution developed by a major Russian company. So, now we officially have our first Russian checkpoint inhibitor that's made it this far. There are a few other drugs under research, but we need more time.

— Is there any chance, however distant, that these drugs might obtain official registration in the Western world, putatively by the FDA?
— I think so. As we continue to gain experience in this field of oncology, which is new to us, I'm confident that our drugs will eventually be recognized elsewhere in the world. I can see how Russian Big Pharma's research approaches are evolving. Whereas before, their studies were, so to speak, specifically Russian, now their research level is close to the international standards. They put top oncologists from Europe on their expert panels, I know that for a fact. They procure auditors from international expert bodies to review their gynecologic oncology studies, for instance. ENGOT, a highly reputable European oncology body, oversees Russian research and gives feedback. So, we're getting close to how things should be done.

— We've pretty much covered the therapy part, but isn't cancer prevention just as important?
— Absolutely! Prevention is a crucial part of oncology. In Russia and pretty much everywhere else in the world, prevention is not the job of oncologists, but of primary care physicians who face the nominally healthy individuals, and are supposed to give them guidance on how to avoid the risk of cancer development. Prevention is a factor in the incidence of disease and, ultimately, also mortality rate. Lung cancer is a good example. In Finland, once one of the world's heaviest smoking nations, lung cancer rates have dropped 80% in consequence of anti-smoking education. Education and explanation are affordable options, and they really work.

— As long as we're on the subject of lung cancer... It is commonly believed that, no matter if or when you quit smoking, if you've ever been a smoker, you're more likely to get lung cancer. Is this true? Does it matter how long the person smoked and what age they are?
— To assess the risk of lung cancer, we need to look at how long the person was a smoker, when, if at all, they quit, and what age they are. Further diagnostic procedures will or will not be prescribed based on this. In the United States, smokers who quit less than 10 years ago and are now over 50 years old get a CT scan of the lungs to catch the tumor at an early stage. If the person quit smoking more than 20 years ago, the risk is minimal and they do not need this procedure.
So, yes, age and duration of smoking are of the essence when it comes to early diagnostics. The same principle applies to women and mammography. Where there's a hereditary history of breast cancer or any lumps in the breast, we prescribe a mammogram.
As for lung cancer prevention, let's just put it this way: no one should smoke. I also urge everyone to vaccinate against the human papillomavirus, this applies to children, women, and men. Some countries have this vaccine on their compulsory vaccination schedule, but not Russia, so you have to get your own shot. This is to minimize the risk of cervical cancer. We're getting increasingly solid evidence that the vaccine really does prevent it. The Cancer Research Bureau predicts that cervical cancer will rank among the top 5 tumors in women by 2035. Vaccination will gradually reduce the risk, but not by 2035. We must realize that all preventive steps and early diagnostics are about long-term effects. We won't be seeing any positive outcome earlier than 20 to 30 years from now, but we have to start right away. Alcohol should be consumed minimally or not at all to avoid the risk of cirrhosis of the liver or other cancers. According to the American Society of Clinical Oncologists' (ASCO) recently released guidelines, it's safe for women to have one glass of wine a day, and two glasses for men. When you exceed these limits, you expose yourself to the risk of liver cancer, esophageal cancer, or other gastrointestinal tumors.
It is also advisable to get immunized against hepatitis B, which is on the mandatory vaccination list in many countries. When it comes to hepatitis C, which is the variant that most often leads to liver cancer, it should be treated, not prevented. HCV patients recover in 96-99% of the cases.

— But first you have to diagnose it. It doesn't always show any symptoms, does it?
— In this case, I can say with pride, Russia is among the world leaders. In Russia, three tests are compulsory at admission to hospital and as part of health checkups: for HIV, hepatitis, and syphilis. Everyone gets those tests done, so we know at any given time how many people we have living with hepatitis. But you have to be hospitalized to get those tests. No other country requires any compulsory tests, neither during hospitalization, nor as part of any health checkups. Another obvious prevention effort should be made in fighting obesity. For instance, kidney cancer is linked to two factors: smoking and obesity, but these factors may contribute to most tumors. Breast cancer is also linked to obesity.

— Are the preventive measures you spoke about statistically valid? How is this verified, by tracking disease progression over time or by exposing correlations with people's lifestyles?
— They are totally valid. They are all arguably meaningful factors in cancer. We can speculate about this, but the fact is, if the person is a smoker, the risk of cancer significantly increases. This is the important point.

— Do you perform surgeries?
— I'm a chemotherapist, but when we do research, we do work that involves surgery and radiation therapy, which, incidentally, has made a big stride. I am a strong believer in medication-based therapy. Tuberculosis was once treated surgically, but now we treat it with medication. My Bureau once performed an illuminating study. Our patient had a small kidney tumor with no metastases. The standard solution now is to remove the kidney or a part of it. That's what our forefathers did: they cut it out. We tried immunotherapy in the hope of stimulating the immune system to destroy the primary tumor, instead of surgical removal. I must admit it didn't work. The tumor didn't go away, but the condition stabilized, and didn't progress any further. That didn't shake my belief that in the future, new therapeutic solutions will allow us to move away from surgical procedures that involve organ removal.

— Tell us a little about your Bureau. How do you organize your work? Do you work with specific clinics or do medical centers come to you? How do you operate?
— When we first started the Bureau, we agreed to adopt the cooperative group model. There are some major cooperative groups in the world. When a study is initiated within the group, the originating researchers, the Bureau in the case, sign contracts and collaborate with several different centers. This work model may be described as a virtual online collaboration, except that it's also hands-on as empirical research is carried out at these different partner centers. One center might specialize in kidney cancer, another in stomach cancer. We believe this is the best organizational model for speedy and productive research, and we get to collaborate with top experts in each field. That's how we operate.

— Sounds like the Bureau has a coordinating role, does it?
— I wouldn't put it that way. We build on an idea. Our role is to formulate the task, develop it into a research protocol, and then organize implementation by engaging other centers. The idea does not have to be ours. Any researcher who wishes to work with us is free to come to us with an idea, and if we like it, we'll try to implement it.

— We've discussed various aspects of treatment development, now I'd like to talk about the hands-on side. The general consensus at this time seems to be that modern medicine is no place for lone heroes, it's all about teamwork and protocol. Would you say that the entire civilized world follows uniform healthcare standards?
— I guess I could say that. The entire civilized world, Russia included, operates on very similar standards. Those standards have recently become quite flexible. Take lung cancer for example. The pertinent international standards have been revised five times in the last year. Those standards used to be revised every five years. But now, with fast-paced progress and the emergence of all these new options, frequent revisions are necessary to keep the standards up-to-date.
Russia follows international practice. The Russian Society of Clinical Oncology has developed the Russian guidelines based on those standards, entitled practical recommendations, which the Ministry of Health and other professional bodies have adopted as their framework standards. I think they are very similar. Perhaps the only difference can be found in the options that have yet to be registered in Russia, but we are catching up fast in that department. Access and execution are another matter. And it needs further deliberation.

— Not at our level, I guess?
— Of course not. Access to new options is a financial matter. High quality medication may cost 600 to 700 thousand rubles, sometimes as much as a million rubles. Not all regions in Russia are able to secure the steady supply of these medications for patients, and yet we note that the number of patients receiving these new medication options has markedly increased. In Moscow, practically all patients can enjoy access to world-class treatment. Some regions have it better, others worse, but this is a matter for the diagnosis-related group (DRGs). This is a separate topic for discussion, not a scientific one.

— How significant is the difference between private and public cancer care in Russia, compared to other countries?
— Private cancer care was tabooed in Russia ten years ago. It was believed that private providers did not have the resources to deliver the full scope of care, unlike public providers. However, we have recently seen a surge in the number of new private cancer centers. Once I served as director of the Hadassah Institute of Oncology, an Israeli clinic. In regards to the Russian clinics I am familiar with (without naming them), I can say that things have really improved there. Some private clinics face all kinds of issues, but there are also some pretty successful private clinics, those that "get it right", so to speak. Their service is no worse than what public clinics offer.

— So, private clinics are kind of second tier?
— It's true, but only because they are restricted in their ability to prescribe drugs and treatment methods to patients covered by obligatory medical insurance (OMI) policy. They are allocated specific quotas, and within their quotas they are not in the back seat, they are actually at the wheel. OMI patients may not be getting the best treatment value for the same money, but they certainly get a more comfortable hospital environment. But when these OMI quotas run out, private providers relapse into the back seat, being unable to deliver all care according to the standards. From this point on, the government no longer covers it and patients have to pay out of their pocket. I believe private oncology should be cultivated in Russia going forward, and perhaps some day a higher percent of cancer care services will be provided by private clinics in Russia. The government ought to share public funds with both public and private clinics. Private clinics are fully funded by investors, and can cost them a fortune. A single CT scanner can price something close to a million dollars. The investor invests their own money, the state doesn't have to pay anything. As I said before, the number of cancer patients is expected to increase dramatically in the near future. When that happens, public clinics will not longer be able to handle all patients. That's why it makes sense to share the burden.  In the US, for example, cancer care is provided exclusively by private clinics. It's covered by insurance, which is the same principle as with the OMI. It works like a charm. In Europe, it's a fifty-fifty deal, but the private sector dominates. We shouldn't be afraid of this.

— What does it take for cancer to lose its terrifying connotations completely?
— There's no other way but to advance science. Contrary to what this might sound like, there's nothing "virtual" about it, it's totally real. We've talked about the Nobel Prize winners before. One lesson the pandemic has taught us is that science is vital, even if its ways are unobvious to the broader public sometimes. The National Cancer Institute (in the US it can be called an unofficial "Cancer Ministry") invests billions of dollars in science, fully aware that 96% of that money will go to waste or yield negative results. But 4% will germinate. The problem is, no one knows which 4% it will be before the funds are disbursed and the work completed. Clearly, we need to invest in science and develop it in order to fight cancer effectively. We've seen tremendous progress in oncology over the past 5 years, all thanks to science. And if we fail to invest in science and advance it, we'll just stay where we are.

— Let's talk a bit about fear. Do you think doctors should be honest with a cancer patient's family and the patient themselves? I'm aware that until recently, Russia's policy in this regard was different from that in the Western world.
— I'm a chemotherapist and I work with patients, so it's a very practical question for me. Unlike the surgeon, I have to tell patients if they have metastases. My cohort are patients with a more unfavorable prognosis. It's painful to bring these things up with them. Legally, we are under an obligation to tell them. The patient who signs an informed consent to treatment is supposed to know everything.
The question is, how do we tell them? You can shock them or you can let them down gently, and then give them some hope that it's treatable. I talk to my patients just like I'm talking to you right now. I break it down for them, explain the options: yes, you have cancer, but we'll fight it, we'll deploy revolutionary know-how to stop and reverse it. But you have to talk to them, that's for sure. I'm pleased to see that outpatient clinics in Moscow have psychiatrists now. They never used to have them before.
I visited Botkin Hospital recently. They also have a psychiatrist's office now. You walk in like it's some private clinic. There is a couch the patient is supposed to lie down on. An experienced professional psychiatrist is in charge. We need these people to help us with what we do. It'll make a difference! Just a few years ago, such facilities were only available in high-end private clinics.
On the occasion of the recent World Kidney Cancer Day, the International Kidney Cancer Patients Association did a survey about the psychological dimension of cancer: how patients cope with their diagnosis and who they feel comfortable sharing it with. The Cancer Research Bureau represented Russia on the project. I found it interesting that Western patients do want to talk about their diagnosis and issues with family or share in patient groups, whereas the Russian patient will only talk about it with the doctor. The Russian patient will often hide the information from family and friends. They don't want to talk about it, except with the doctor. And it brings us back to the question of psychological help, we should support this.