Darwin was right

For the past 25 years, evolutionary biology has been applying its Darwinian approach to medicine, offering innovative therapies to combat certain diseases, including cancer. The Centre de recherches écologiques et évolutives sur le cancer is a pioneer in this approach, based on the principle of natural selection.

"Everything living can be studied through the prism of natural selection, since everything has been under the influence of this process for as long as life has existed on earth," declares Frédéric Thomas, researcher at the Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (Mivegec) laboratory. And cancer, a living entity within our own bodies, is no exception to this rule theorized by Darwin over 150 years ago.

For this evolutionary biologist, author of L'abominable secret du cancer, "it's time to work with doctors to solve, together, the problem of resistance to treatment, the leading cause of death among patients". For if chemotherapy is effective when it manages to eradicate all cancer cells without killing the patient, what happens when some of them survive the treatment?

Maintaining competition between cells

By disappearing, chemotherapy-sensitive cells leave the way open for resistant cells to develop, causing relapses that we no longer know how to treat. "If we apply a very aggressive strategy to a tumor, the resistant cells will win twice. Firstly, because they are not killed, and secondly, because they no longer have any competitors. This is the scenario you absolutely must avoid," warns Frédéric Thomas.

Faced with this situation, evolutionary medicine advocates so-called adaptive therapies. A light, regular treatment that kills only a small proportion of sensitive cells to prevent the cancer from progressing. "We cut off the branches that stick out, but maintain competition between sensitive and resistant cells, so that the tumor remains stable. A cancer treated as a chronic disease, incurable of course, but without mortal risk for the patient.
While these treatments seem to be proving their effectiveness in the United States, the researcher warns: "These therapies only apply to cancers that have become impossible to eradicate. If a tumor has not begun to spread, it must be removed.

Fighting cancer

To maintain competition between cells, biologists are also testing the use of fake drugs. Why? If resistant cells survive chemotherapy, it's thanks to small pumps that enable them to evacuate the poison. A huge advantage, but not without cost, since these pumps consume a lot of energy. "If you use a fake drug that mimics the effects of the real thing, the resistant cells will exhaust themselves activating their pumps for nothing, so you'll be giving the edge to the sensitive cells, which don't have pumps. A therapy which, when used in alternation with a real poison, will weaken both resistant and sensitive cells, thus maintaining the tumor in a stable state.

The third therapeutic avenue being explored by evolutionary biology is that of the "false alarm". Highly unstable genetically, cancer cells constantly cause damage to their own DNA, which they have to repair. Frédéric Thomas and hisInstitut Curie colleague Marie Dutreix designed a molecule capable of mimicking a DNA damage signal, and inundated the cells with it. The result: the cells are in a state of panic, trying to repair their DNA on a massive scale and exhausting themselves without any benefit.

The false alarm

The only way it can resist is to stop responding to the alarm signal. It's a universal response", explains the researcher, "when the rate of false alarms increases, the threshold beyond which we will respond also increases, even if it means putting ourselves at risk in the event of a real attack". And this is obviously what the researchers will do, after ten weeks, causing real damage that the cells will then be unable to repair.

Highly promising research that motivated Frédéric Thomas to found the international Cancer, Ecology and Evolution laboratory in 2018, whose partnerships will soon extend from Australia to Florida. "Montpellier is the heart of the volcano, with the world's largest scientific community in evolutionary biology. We have the intelligence and the motivation, we just need the means to become the stronghold of evolutionary medicine." Let's hear it...