Cancer: "Let's be careful not to give false hope to the sick"

The major congress of the ASCO (American society of clinical oncology) takes place until Tuesday in Chicago. Like every year, many innovations and advances are presented. But are we really making progress in the fight against cancer?

Christophe LeTourneau*: The cure rate was 20% before World War II. With the arrival of chemotherapy, we went to 50%. Essentially by curing hematological diseases and certain so-called “solid” cancers such as testicular cancers, which respond very well to this treatment. Then, in the 2000s, thanks to a better understanding of cancer biology, we discovered targeted therapies. The cure rate reached 55%. With immunotherapy, this rate has increased further, to 60%. These are orders of magnitude of course, but we can clearly see that we have not yet solved the problem.

Cancer is always scary, and for good reason! Every year, in June, we are very happy with the considerable progress we are making, but unfortunately many patients still die of their cancer. It’s very different from what happened for AIDS with the development of effective treatments in ten years. AIDS patients now have the same life expectancy as the rest of the population, with few side effects from their drugs. We are still far from it in oncology, because cancer is a much more complex disease. We succeed in prolonging the life of patients with relapses or metastatic disease, but more often than not we do not cure them.

Limited offer. 2 months for 1€ without commitment

You hold a rare speech for an oncologist…

Do not mistake yourself. I am optimistic, and I am delighted with all the results that are presented. Of course there is hope. But you still have to moderate the words. If we take a step back, we see that our results are not satisfactory. I am always very careful not to create false hopes. Claiming, as we can sometimes read, that we have found a way to overcome this disease when the results presented are in the preclinical stage (on animals, editor’s note), it is always difficult for the patients who then call us in believing that we will be able to cure them.

No two patients have exactly the same disease from a biological point of view. This is why immunotherapy was attractive: instead of attacking the tumor frontally, the patient’s immune system is reboosted, which is then supposed to eradicate the cancer. It’s a smart approach. But it quickly turned out that it only works on a minority of patients, without anyone understanding exactly why. Response rates are 40% in melanoma, 30% in lung cancer, and roughly 10% to 20% in other organs. And again, when I speak of response rate, it is a reduction in the size of the tumor, not a cure, which concerns less than 5% of patients.

“Twenty years from now, you will do full imaging every year that will identify cancer cells”

Yet you say there is hope. Where do you think it will come from then?

I think it’s really early diagnosis that will one day get rid of cancer, more so than therapeutic progress. We can already see it today: the key to any prognosis is linked to the stage at which the disease is discovered. A little colon cancer, you operate on it and we don’t talk about it anymore. Cervical cancers continue to kill in Africa or Latin America, as women present with very advanced tumours. In Europe, with vaccination and Pap smear screening, the incidence of this cancer is much lower and diagnoses are often made at earlier, still curable stages.

Today, screening is generally not very effective…

It is not precise enough, and generates a lot of “false positives”, disturbing results that ultimately turn out to be false alarms. As a result, participation is insufficient. But we will certainly have in the future more and more advanced functional imaging techniques, which will allow us to distinguish on the screen what is cancerous from what is not. We can imagine that in twenty years, you will do complete imaging every year that will identify cancer cells thanks to antibodies specific for cancer mutations, which cling to tumor cells. Then, it will suffice to make these same antibodies irradiating so that they destroy these cells. This already exists, moreover, for prostate cancer or endocrine tumours. I strongly believe in the development of this type of screening.

More than in liquid biopsies, these blood samples where we look for specific markers of lesions, whether they are traces of tumor DNA or cancer cells?

The problem is that when a cancer is very small, we do not detect tumor DNA circulating today. This technology is not yet sufficiently sensitive: today, it can only detect patients with recurrences, or monitor the effectiveness of treatments.

We still hear about a lot of innovations: new drugs, car-t cells, therapeutic vaccines… Don’t you believe it?

On the treatment side, there are many novelties that are effective in some patients. The great advances of the moment are linked to antibody-drug conjugates (“antibody drug conjugate” in English). We were already using monoclonal antibodies, but here they are associated with a bubble containing chemotherapy. This makes it possible to use more powerful molecules, which could never be given intravenously because they were too toxic! There, the antibody latches onto the cancer cell, and the drug is dropped directly into the targeted cancer cells. But we always come back to the same problem: these innovations prolong survival, they do not cure most of the time.

As for CAR-T cells, these are T lymphocytes genetically modified to attack tumours. It is a cutting-edge technology, of great complexity, and all the same sometimes very toxic, with patients who can sometimes spend one or two months in intensive care after their administration. It is far from trivial. Despite everything, formerly condemned patients recover, in particular in certain leukemias and lymphomas. In solid tumors, on the other hand, this is not yet convincing. To tell the truth, if I had to take a bet, I would mainly bet on therapeutic vaccines.

What is it about ?

From another form of immunotherapy, since it is a question of educating the immune system. We are currently testing an anti-HPV 16 vaccine. The human papillomavirus (HPV) can cause various tumors: cervix, ENT sphere, anal canal, penis, vulva… To construct the vaccine, simply introduce in an inactivated virus a DNA sequence of HPV. Once injected, the patient’s immune system will come into contact with this DNA sequence, and will develop T cells that will attack cancer cells caused by HPV.

Another example is personalized therapeutic vaccines, which are for example developed in France by the company Transgene. From the sequencing of a patient’s tumor, mutations are selected and the corresponding DNA sequences introduced into inactivated viruses. Patients are vaccinated, and their immune system produces T cells directed against these mutations.

In ovarian cancer, a first patient was treated this way in the United States. Her tumor was operated on, and when a blood biomarker showed she was relapsing, she was vaccinated. After injection, the biomarker normalized. This is an extraordinary proof of concept, which now needs to be confirmed on a larger scale. A clinical trial is underway, in which the Institut Curie is participating, in ovarian cancer and ENT tumours. We will have the results in two to three years. But there are many other trials, with other DNA or messenger RNA vaccines. These are revolutionary technologies, in the sense that they make it possible to manufacture these vaccines very quickly.

Why would it work better than the immunotherapies currently used?

Because this time it’s about personalized treatments, truly adapted to each patient. Immunotherapy, on the contrary, is not specific. But you always have to be careful. We do not yet know if the vaccine alone will be enough to strengthen the immune system or if it will have to be combined with another immunotherapy, or if the tumor will be able to put in place bypass mechanisms. In addition, questions still arise about the relevance of the targets and the moment when the vaccine is administered. There will always be the risk that the mutations selected are not the right ones. Perhaps it will work better in the case of residual diseases, after an initial treatment with surgery and radiotherapy, to prevent recurrences. If so, it would still be a truly spectacular step forward, because today, it is these patients that we have the most difficulty saving.