[LUM#11] Darwin Was Right
For the past 25 years, evolutionary biology has been applying its Darwinian approach to medicine and developing innovative therapies to combat certain diseases, including cancer. The Center for Ecological and Evolutionary Cancer Research is a pioneer in this field, which is based on the principle of natural selection.
“Everything that is alive can be studied through the lens of natural selection, since everything has been subject to this process ever since life first appeared on Earth,” says Frédéric Thomas, a researcher at the Infectious Diseases and Vectors: Ecology, Genetics, Evolution, and Control (Mivegec) laboratory. And cancer—a living entity within our own bodies—is no exception to this rule, which Darwin theorized more than 150 years ago.
For this evolutionary biologist, author of the book *The Abominable Secret of Cancer*, “it is time to work with doctors to solve, together, the problems of treatment resistance, the leading cause of death among patients.” For while chemotherapy is effective when it succeeds in eradicating all cancer cells without killing the patient, what happens when some of them survive the treatment?
Maintaining competition among cells
As the cells sensitive to chemotherapy disappear, they leave the field open for resistant cells to grow, 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 over. First, because they aren’t killed, and second, because they no longer have any competitors. This is the scenario we must absolutely avoid,” warns Frédéric Thomas.
In response to this situation, evolutionary medicine advocates so-called adaptive therapies. This involves mild, regular treatment that kills only a small portion of the sensitive cells to prevent the cancer from progressing. “We trim the overgrown branches but maintain the competition between sensitive and resistant cells so that the tumor remains stable. ” Cancer is treated as a chronic disease—incurable, certainly, but not life-threatening to the patient.
While these treatments appear to be proving effective in the United States, the researcher cautions: “These therapies are only applicable to cancers that have become impossible to eradicate. If a tumor has not begun to spread, it must be removed.”
Outwitting Cancer
To maintain competition among cells, biologists are also testing the use of decoy drugs. Why? If resistant cells survive chemotherapy, it’s thanks to tiny pumps that allow them to expel the poison. This is a huge advantage, but it comes at a cost, since these pumps consume a lot of energy. “If we use a decoy drug that mimics the effects of the real one, the resistant cells will exhaust themselves by activating their pumps for nothing, and you’ll therefore give the advantage to the sensitive cells, which don’t have pumps. ” This therapy, when used alternately with a real toxin, will weaken both the resistant cells and the sensitive cells, thereby keeping the tumor in a stable state.
The third therapeutic approach explored by evolutionary biology is known as the “false alarm signal.” Cancer cells are genetically very unstable and constantly cause damage to their own DNA, which they must repair. Frédéric Thomas and his colleague atthe Curie Institute, Marie Dutreix, designed a molecule capable of mimicking a DNA damage signal and flooded the cells with it. The result: thrown into a state of panic, the cells attempt to repair their DNA on a massive scale and exhaust themselves without any benefit.
The False Alarm
The only way for it to resist is to stop responding to the warning signal. “It’s a universal response,” explains the researcher. “When the rate of false alarms increases, the threshold above which we respond also rises—even if it means putting ourselves at risk in the event of a real attack.” ” And that is, of course, exactly what the researchers did after ten weeks, causing actual damage that the cells would then fail to repair.
This highly promising research inspired 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, home to the world’s largest scientific community in evolutionary biology. We have the intelligence and the motivation; all we lack are the resources to become a powerhouse in evolutionary medicine.” A word to the wise…
A Contagious Cancer
Known to the general public as Taz, the whirlwind cartoon character, the Tasmanian devil is now an endangered species. The cause? A previously unknown and contagious form of cancer that biologist Frédéric Thomas is studying closely: “This cancer appeared 26 years ago and has decimated 90% of the devil population. We’re trying to understand how this disease became contagious.” Transmitted through bites, it manifests in the small marsupial as purulent tumors and causes death within six to eight months. “The good news is that we’re starting to see resistant devils. The bad news is that a second contagious cancer has emerged,” notes the researcher, who will be back in the field as early as November to observe them.
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