César Rodríguez, oncologist: “Cancer is like a ‘coup’ of your own cells”

You never know where life takes you. César Rodríguez (Salamanca, 54 years old) was going to be a biologist, but ended up studying Medicine. During his studies, he says, he pursued his professional career away from patients, in the field of research and the laboratory—microbiology or biochemistry, perhaps—but he learned about clinical and healthcare medicine and settled at the end of his studies as an internal student. of cardiology. That was his final destiny until he wasn’t. Until, “in the last breath”, in a random rotation through the oncology area, he discovered, with the help of his mentor, Dr. Juan Jesús Cruz, a discipline and a world that he hardly knew anything about. “Cancer, at that time, in 1993, was still an almost always lethal disease, with very few treatment options. It was a specialty where everything had to be done,” explains the doctor, who is an oncologist at the University Hospital of Salamanca, now.

30 years have passed since those first turns in life that, against all odds, led him to oncology and, although the study of cancer has taken a giant leap, it still remains an enigmatic disease, admits Martínez, who has just debuted as president of the Spanish Society of Medical Oncology (SEOM) at the congress that the scientific organization held this week in Barcelona.

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Ask. He says that, when he started, it was a discipline in which everything had to be done. Now, 30 years later, has everything been done?

Answer. Much of what we thought was yet to be done has been done, especially to understand tumors. But everything remains to be done because if we already knew everything we would be curing most of the tumors. What’s left to do now? Knowing the mechanisms of resistance to the treatments we use is probably one of the challenges we have. Also know why in some cases in which we have very well designed treatments to address a very specific therapeutic target, we still do not have homogeneous efficacy in all patients: what differentiates patients who do very well with a treatment compared to to those who are not doing well; and then there are much more basic challenges: early diagnosis, the challenge of not having to treat but rather prevent, at a social level continues to be a problem. We have not yet managed to reach the point where we diagnose tumors in very early stages.

Ask. Oncologist Siddharta Mukherjee said in an interview in EL PAÍS that cancer continues to be one of the greatest mysteries of medicine. What do you think?

Answer. Cancer is one of the greatest mysteries of medicine because cancer is a revolution of your own body, it is like a coup d’état of your own cells. Here it is your own DNA, your own cells, your own identity that turns against you: it undergoes certain modifications that make its behavior, which has always been to go with you and help you repair tissue when it is damaged, turn against you. They are the ones that have always served you to help you solve problems, the ones that cause you harm and also, they do it in a very well prepared way. If cancer were simply disordered proliferation of cells, it would never kill and surgery would cure most tumors. Cancer is capable of growing, proliferating and, at a given moment, saying: “We are not satisfied with the problem we have created here and now we are going to look for ways to escape.” And these escape routes are much more complex than we think: not only is cancer capable of metastasizing because it sends cells out there, because if that were the problem, our immune system is quite smart and is capable of identifying what is foreign. and would destroy it. It is capable of escaping and is able to circumvent our immune system’s own recognition systems in a very intelligent way. That is, I grow, I proliferate, I escape, I am able to outwit (the immune system) and I proliferate again in territories that were not the most suitable for me. That’s what makes cancer such a difficult disease to understand. And it turns out that when you have discovered the mechanism by which a tumor grows and you find a treatment strategy that can harm it, it is capable of developing resistance, escape routes to treatment.

Q. Is it survival instinct, in the end?

A. Yes, but in a very programmed way. The complexity of our own cells means that tumors also have these escape routes. Our cells are designed, for example, to be able to regenerate and this capacity for regeneration is what makes tumors also immortalize. And we also know that tumors have behaviors, growth and proliferation mechanisms, so different from each other that we are talking about dozens of different diseases that have nothing to do with each other: there are breast cancers that are more similar to certain types. of lung cancer when we analyze them from a genomic point of view.

Q. What is it that is not fully understood about cancer?

A. In many tumors, we know the mechanisms that lead to their development, but we do not know the primary cause. When we know it, we will understand much better everything that goes behind it. In some tumors we do know: knowing that the cause of cervical cancer is infection by the human papillomavirus has meant that, with vaccination programs, in the future, in our environment, this tumor will be anecdotal.

In many tumors, we know the mechanisms that lead to their development, but we do not know the primary cause. “When we know it, we will understand much better everything that goes behind it.”

Q. What if the cause is chance? A random mutation, for example.

A. When a change occurs that leads to the development of a tumor, generally speaking, something else has to go wrong. I once heard a teacher in a class in Salamanca say that we all get cancer every day, but we have mechanisms that prevent that from happening anymore. Mechanisms that, when a cell mutates or proliferates in an inappropriate way, lead that cell to programmed cell death; or mechanisms that identify this proliferation as foreign so that your immune system can eliminate it. Under normal conditions we are prepared so that all those alterations, those mutations that we have every day, do not get worse. The question is why in some cases this does not happen.

Q. Cancer has always been associated with aging and the forecast is that cancer numbers will rise because life expectancy also increases. But tumors in young adults are also increasing. What’s going on?

A. You can never look for an explanation with a single factor. You always have to look for an accumulation of things. Fundamentally, this is happening in Western countries, where environmental factors and lifestyle habits related to the development of tumors have become more frequent: we are seeing a population that is globally more overweight, with a diet that is not the most appropriate, alcohol consumption very high, a smoking habit that we are not able to stop, excess calories in the diet, a sedentary lifestyle… Exposure to environmental risks, such as pollution, is probably another factor. If you put all this together, it is logical to think that in a Western society that increasingly exposes its citizens to risk factors sooner, you will have tumors sooner. And then there’s another factor: Detection at younger ages is also sometimes linked to better diagnostic techniques.

Q. Regarding secondary prevention, in the presentation at the SEOM congress, you warned of the need to refine screening, including moving towards molecular screening. Where do you want to go?

A. We cannot do what is difficult before knowing how to do what is easy. Breast cancer screening, which cost a lot to make universal, is a reality, but in colon cancer there is still a way to go. Before we think about more sophisticated things, let’s do the easy things first. But it is true that, at a certain point, you have to realize that screening programs have to be aimed at the populations in which you can obtain health results: it is not feasible to do a CT scan on the entire population to look for any tumor, but we know that there is solid data that certain radiological studies in the smoking population will allow there to be less mortality from that cause. It will be necessary to combine population screening programs, where you know that you benefit a large population with a simple and affordable test, with those more selective programs in at-risk populations.

Q. Last week a study was published on breast milk screening to detect tumor DNA in breast cancer during the postpartum period. In the long term, will there be more refined screening, such as molecular testing?

A. The scientific community is convinced that molecular screening will be a reality. The ability to detect molecular alterations that indicate that there is a tumor and the origin of that tumor, technically, is already a feasible reality, but it must be refined. The study with breast milk samples is fantastic. Other examples are that with the determination of circulating DNA in peripheral blood we will have to, with a blood test, identifying certain molecular alterations, you will know that that person is at risk or is already incipiently developing a tumor. That will be an indisputable reality. What we don’t know is when we will be able to implement it.

“We all get cancer every day, but we have mechanisms that make it stop.”

Q. In the congress presentation you also mentioned tertiary prevention, in former cancer patients. What does it refer to?

A. Today we know that certain behaviors, after having had a tumor and being cured, allow us to reduce the risk of relapse as much as, and sometimes more than, some treatment strategies. That is, in women who have had breast cancer that has been adequately treated, in the years following that diagnosis and potentially curative treatment, there is a proportion that relapses, but we also know that, if these women, fundamentally, are postmenopausal, have a normal weight and do well-scheduled physical exercise, have an adequate diet and do not consume alcohol, their risk of relapse is significantly lower.

Q. Regarding treatment, there has never been as much therapeutic arsenal as there is now. What are they missing?

A. We have a huge arsenal and it is increasingly selective. What is needed now is to identify the populations that benefit from a specific therapeutic strategy. We still have very modern strategies that, despite the fact that they act on a specific molecular target, when we use them, we see that there is still a population that does not respond.

Q. For example?

A. With immunotherapy we have been able to identify in some tumors that the most responsive patients are those who have, for example, an expression of a receptor that is PDL-1 or PD-1. But in certain types of tumors, such as triple-negative breast cancer when we use it in neoadjuvant treatment (before the main treatment), PDL-1 does not play a role in saying who responds and who does not, so it is he puts it to everyone. Although we believe that we have very precise medicine, we have to continue refining the mechanisms that are capable of identifying which patients truly benefit so as not to subject those who do not to treatment.

Q. The population is still afraid of the word cancer.

A. There is still fear about the word cancer, but it has been greatly destigmatized. We have made a lot of progress in making cancer visible as something normalized, but another thing is the stigma that cancer kills: there is still a long way to go. It is true that cancer continues to be a disease with a high mortality rate and as long as it has a high mortality rate, it will continue to be a disease that transmits fear and fear. There is only one option here: we have to continue improving therapeutic results and transmit them to the population so that they understand that, at this time, certain tumors that previously had a poor prognosis, we are now capable of allowing patients to live with the disease and have a normalized life.

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