La génétique donne des informations précieuses sur le cancer. UNSPLASH – NATIONAL CANCER HEALTH INSTITUTE
Professor Pascal Pujol, a geneticist specializing in cancerology, heads the oncogenetics department at Montpellier University Hospital and chairs the French Society for Predictive and Personalized Medicine.
Diagnosis, prevention, treatments… genetics is revolutionizing the approach to cancer, says oncogeneticist Pascal Pujol, while World Cancer Day, this Tuesday, February 4, is marked by great hopes for treatment, and an observation: with 433,136 new cases in 2023 (source: National Cancer Institute), cancer is the leading cause of death in France. 3.8 million French people are currently living with a cancer diagnosis, recalls the Inca.
Pascal Pujol gave a public lecture on Friday, January 31, in Montpellier, “What genes say about our health”, on the occasion of a conference organized by the League against cancer.
Pascal Pujol: “I spent twenty years fighting with doctors who said that genetics is a fad”. DR – HANNAH ASSOULINE
Genetics and cancer, the link seems obvious today, but it has not always been so: twenty years ago, you were one of the pioneers, you opened the oncogenetics consultation at the Montpellier University Hospital.
Yes, there were two “levels” in fact. First, the question of family predispositions to cancer. To date, we have seen 30,000 patients at the University Hospital.
The second important point is the advent of targeted therapies: in the last twenty years, treatments have arrived to target a genetic anomaly on the tumor. The growth is considerable. Today, we have 122 treatment indications on 70 genetic markers. For example, for lung cancer, we have 10 drugs on 10 different genetic markers. Many colleagues did not believe it, and that is still the case. I spent twenty years fighting with doctors who said that genetics was a “fad”.
The American FDA publishes a report every year on drugs put on the market. The latest one came out this week: 30% of new drugs are targeted therapies. Each time, we try to develop strategies to overcome the genetic anomaly.
With what types of treatments ?
Immunotherapy can be part of it, it works in 10% to 15% of cases. Before administering it, we need to know if the patient will be sensitive to it, for this we have a genetic marker of the tumor that allows us to know, MSI (for micro-satellite instability).
We also have CarT-Cells for liquid tumors, which are coming in myeloma and solid tumors, and drug-conjugated antibodies, chemotherapies guided by a molecular marker, for about ten indications. Here, you use a molecular marker of a tumor (bladder, breast, lung, etc.). If the cancer cells express a particular gene, you will use the antigen to attach chemotherapy to it. The drugs can be even more powerful, and it is incredibly effective.
Finally, we have about thirty “drug-conjugated antibodies”, i.e. chemotherapy + antibodies, in clinical trials today. We need to find a specific tumor marker, and from there, attach a drug. Here too, they are very powerful, they would be deadly if they were not so targeted.
200% Deposit Bonus up to €3,000 180% First Deposit Bonus up to $20,000“The whole problem is to have the molecular marker of the type of cancer”
All this would not be possible without genetics…
No.
All types of cancer are affected by advances in genetics ?
The whole problem is to have the molecular marker of the type of cancer. Where it works best today is the lung, the bladder, the breast.
How far has progress gone?? Let's take a woman who has the BRCA 1 or BRCA2 genetic mutations, to take one of the best-known genetic predispositions to the very high risk of breast cancer. Can we offer her a drug that inhibits gene expression or should she remain under close surveillance, or even have her breasts removed??
We set up a trial on the subject in 2007. It was opened in thirty centers in France. We offered women who had a BRCA mutation a drug known to reduce the risk of breast cancer, it is a hormonal therapy, against a placebo.
We had results last year: unfortunately, the result is negative. The hormonal treatment has no effect.
We must ask ourselves the question again with new drugs. But there is the problem of side effects.
“Any child who has cancer is seen in an oncogenetic consultation”
BRCA, for the breast therefore, has equivalents in other cancers ?
BRCA is the most common gene, it affects one in 200 people, but we have 80 syndromes! But not all of them lead to ablations. We do it for ovarian cancer, linked to BRCA or other genes, and thyroid cancer, because the cancers are very aggressive.
Of the 80 syndromes, about twenty are in children. Today, any child who has cancer is seen in an oncogenetics consultation, and we have a positive result in 10% of cases.
Then, in adults, the breast and ovary represent 60% of our consultations. And then 15% of digestive (colon, pancreas, stomach). We also have lung cancers that are familial, endometrial cancers, uterine cancers, prostate cancers… We don’t see enough of the people concerned, even though we can have preventive and therapeutic action.
Cancer and genetics: mechanisms that are increasingly well-known. Midi Libre – SOPHIE WAUQUIER
Tomorrow, we could have preventive screening based on predictive genes for known cancers ?
The question was considered as part of the revision of bioethics laws. We didn't go any further. But I think we will move towards that, by refining knowledge on the risks, and the strategies.
All cancers are linked to a genetic anomaly ?
Yes, all cancers have genetic mutations, but not in the sense that we understand them. Family inheritance is 10%. Most often, it is events that create acquired mutations. Example: ultraviolet radiation creates mutations in skin cells. And these mutations lead to cancer. We could also mention tobacco smoke which causes mutations in the genes of the lung epithelium.
But in both cases, we have new, very effective treatments to treat them.
“Genetic tests must be done properly, this is not the case everywhere”
We are only at the beginning of the genetic “revolution” ?
The first targeted therapy is twenty years old. In 2000, there were about ten molecules under evaluation. In 2010, there were 10 approved molecules, 100 under evaluation. In 2020: 100 approved, more than 1000 under evaluation. In 2024, 122 approved.
Today, we can talk about a cure.
How can we not think that in ten years, we will not have done better? And there is one thing that has not been talked about: there is not only targeted therapy. The genetic information of the tumor can also be an indication, or not, of treatment, chemotherapy for example.
This is a way forward, knowing that genetic tests must be done well, this is not the case everywhere. There is inequality across the territory.
Genetics remains as promising as AI in cancerology ?
AI will be especially relevant to guide towards the best treatments, it will help with decision-making. Things are becoming extremely complex because we have a lot of data, several therapeutic avenues. They will become even more so.
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