Pink October, breast cancer screening awareness month, begins on Sunday. The opportunity to ask Bruno Quesnel, research director at Inserm, if advances in medicine made it possible to see possible cures for patients suffering from different forms of this disease.
They affect the breast, lung, colon, prostate, skin, liver, stomach… And are one of the main causes of mortality. Cancers were the cause of nearly 10 million deaths worldwide in 2020, or nearly one in six deaths, according to the World Health Organization. In France, breast cancer alone is diagnosed in nearly 60,000 people each year, causing 12,000 deaths, according to Public Health France. However, despite a national screening program that invites women aged 50 to 74 to have a mammogram every two years, less than half of them perform this examination.
On the occasion of the launch of the annual Pink October awareness campaign, Sunday October 1, franceinfo spoke with Bruno Quesnel, director of the cancer thematic institute of the National Institute of Health and Medical Research (Inserm ), and also responsible for research and innovation at the National Cancer Institute. An interview to understand where the research is on this disease and the treatments to cure it.
Franceinfo: With the increase and aging of the population, the number of cancers has doubled in France since 1990. Is there a tendency to develop more cancers?
Bruno Quesnel: Not really. In fact, 60% of cancers are said to be “inevitable”, because they come from the aging of our cells. During our lives, our cells divide, and in copying their DNA, they make errors which induce mutations. It’s a bit like when you make a photocopy of a text, then a photocopy of a photocopy… In the end, the text becomes totally illegible. This natural phenomenon is present in all complex organisms: when a population ages, the number of cancers increases, it is unstoppable.
Promising new treatments for various cancers were announced in June. A therapeutic vaccine against cancer lung was also presented in September. Does 2023 mark a turning point in medical research?
I do not believe. You have to be very careful with these kinds of announcements. There are some every year at the end of the Asco congress [le plus grand congrès international de cancérologie, qui se tient chaque année en juin à Chicago, aux Etats-Unis]. Sometimes these announcements can indicate progress following therapeutic trials, without these necessarily changing the situation, or only very partially.
“With my thirty years of experience, I would say that there is on average one major therapeutic advance per decade.”Bruno Quesnel, research director at Inserm
The big breakthrough in the 1990s, for example, was the discovery of monoclonal antibodies. [des anticorps fabriqués par des cellules en culture pour traiter des maladies spécifiques]such as rituximab, which allow in particular to better treat certain lymphomas [des cancers qui affectent certains globules blancs]. Then, during the 2000s, appeared the targeted therapies, which target mechanisms specific to tumor cells. The 2010s were marked by the emergence of immunotherapy, which stimulates immune defenses against cancer cells. It comes from research that was carried out in the 1990s and early 2000s.
We will see what progress will be made in the 2020s. We must be aware that the therapeutic avenues that are being tested today on humans come from fundamental research that dates back more than fifteen or twenty years.
How has the discovery of immunotherapy constituted a major advance in treating cancers?
To put it simply, our immune system is designed to recognize anything that is foreign to it. It is designed to destroy parasites, viruses, bacteria… Anything that can contaminate us. It can also recognize cancer cells. However, it does it badly and does not prevent neoplastic conditions [c’est-à-dire les tumeurs ou les cancers] to develop oneself. We therefore searched for a long time how to solve this problem, by trying to stimulate it.
This is how we made a major discovery, by identifying the brakes of the immune system, which was also the subject of a Nobel Prize awarded to two researchers, Tasuku Honjo and James Allison. When you develop a condition, your immune system must fight it off without getting carried away. Once it has fought off this virus, it must return to a normal functioning state. To do this, it uses moderating molecules, which cancer cells use a lot to evade the immune response. We have therefore identified these brakes and developed blocking antibodies, which prevent these brakes from acting.
During clinical trials, we demonstrated that we could achieve spectacular responses for certain cancers. One of the best examples concerns malignant melanoma, a very serious skin cancer. He responds very, very poorly to radiotherapy and there is no effective chemotherapy. Immunotherapy makes it possible to modify the progression of cancer, and even to provide a complete response to the disease for certain patients. However, it does not work on all types of cancers, nor on all patients. This is a general rule in oncology: there is no treatment that works 100%.
Besides treatments, are there other advances that make it possible to better treat more patients?
We can improve patient prognosis with new diagnostic tools. For example, many acute leukemias [des cancers du sang] that occur in adults require a bone marrow transplant. However, these grafts can be toxic for certain patients. Thanks to DNA sequencing, we can now determine in which patients this transplant will be beneficial, and in whom it should be avoided.
“DNA sequencing has made it possible to increase the long-term survival rate of people aged 18 to 60 affected by leukemia from 30% to 45%, even 50%.”Bruno Questel, research director at Inserm
This DNA sequencing has also enabled another important progress over the last twenty, even thirty years: that of having created categories and subcategories of cancers. This allows doctors to define entities that will respond differently to treatments. Before, you were told that you had lung cancer. However, there are several types, with DNA mutations which cause very diverse forms. Today, we must instead use the plural and talk about lung cancer, with many different categories. Some will be sensitive to immunotherapy, and others to targeted therapies.
During the pandemic, messenger RNA made it possible to develop vaccines against Covid-19. It is also an avenue explored in cancer research. Will this technology also make it possible to cure patients suffering from this disease?
Our immune system is a kind of xenophobic tool, which destroys everything that is foreign to our body. However, cancer comes from our own cells, which means that our immune system cannot detect and hunt it as well as an external virus.
In the case of cancer, the cells are already there, like a sort of spy that has infiltrated the body. Messenger RNA could allow our immune system to identify this spy and destroy it. But again, these are only leads: there are some encouraging results, but it will probably take more than a decade to know if these leads are really interesting.
Does artificial intelligence represent hope in the fight against cancer?
Artificial intelligence especially helps research. Even more so with the tools we have today, such as DNA and RNA sequencing and all the ways of characterizing cancer cells, which generate an absolutely colossal flow of data. AI helps us identify interesting research avenues in this stream.
We can also use AI for clinical research, particularly for diagnostic and prognostic tools. Perhaps this will become the routine of the coming decade. However, it is necessary to prove that these tools can provide a real benefit compared to the interpretation of a doctor or a researcher.
You can estimate that AI does just as well in terms of interpretation results, but it also needs to demonstrate its impact on patient survival. However, for this to happen, we will have to spend years and years to collect long-term monitoring data. But what is certain is that we will no longer be able to do without it in terms of research.
With these technological advances, will we eventually be able to treat all cancer patients?
To answer this question, we must look at a long time scale – several decades in oncology. I think that we will be able to cure all neoplastic conditions in fifty or a hundred years, since we have several therapeutic avenues.
“We have a better understanding of the processes that lead to the development of cancer and, more importantly, its progression.”Bruno Quesnel, research director at Inserm
The general public must understand that the time required for scientific research and clinical validation is very long. Because once you arrive at a treatment that can be used in humans, you have to test it, then begin a whole phase of clinical trials, before having them validated. Finally, you must be able to justify the benefit of a drug in therapeutic and public health terms. All this can take a decade.
This time is difficult to compress. You can accelerate fundamental research by putting more resources into it, using more powerful IT tools. But if you want to judge the effectiveness of a drug, you need years of hindsight. What we want to know in cancerology is whether a new treatment allows patients to survive long enough to consider them cured.