Natural selection: fighting cancer, drawing inspiration from the genius of Darwin

Natural selection: fighting cancer, drawing inspiration from the genius of Darwin

215 years ago on this day, February 12, 1809, the famous English scientist Charles Darwin was born, whose ingenious work on the evolution of living species revolutionized modern science. This fabulous legacy left by Darwin is still relevant today and may even play a leading role in the discovery of new cancer treatments.

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Charles Darwin

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Darwin’s great discovery was that he observed that the great diversity that existed between individuals of the same species, especially when they lived in different environments, was the result of biological transformations that enabled them to adapt to that environment.

People who are better adapted are more likely to survive longer and therefore more likely to pass on those characteristics to their offspring.

Cancer is a Darwinian disease

Thanks to this natural selection, the life of all organisms, from simple viruses to complex animals such as humans, is a very dynamic process, in constant evolution since their appearance on Earth.

Darwin, of course, did not know this when his work was published in 1859, but the evolution he described at the macroscopic level of living species also applies at the microscopic level of cells.

For example, when cancer develops, a cell manages to acquire genetic characteristics that give it a growth advantage over normal cells.

If these new properties allow it to better adapt to the microenvironment in which it finds itself, this abnormal cell will win competition with normal cells and eventually become the dominant cell species, forming a mass that invades the organ: this is clonal selection. .

Darwin’s principles of natural selection also work in treating cancer.

For example, a high dose of chemotherapy often kills the vast majority of cancer cells, but it only takes one cell (clone) to become resistant to treatment for this characteristic to be passed on to its descendants and create a population of resistant cells that will cause the cancer to recur and make it resistant to future cancers. methods of treatment.

Antitumor therapy

It has recently been suggested that the Darwinian approach may also be useful in treating some types of cancer, especially prostate cancer. (2).

The principle of this approach is that rather than trying to completely eradicate cancer cells with aggressive chemotherapy, which generates resistant cells that have adapted to the drug, we instead aim to control tumor growth without eliminating it entirely by controlling its exposure to chemotherapy agents.

Thus, cancer cells that become resistant are in direct competition with non-resistant cancer cells (that were not killed by low doses of treatment), which limits their growth and prevents the emergence of resistant, incurable tumors.

This resistance to conventional chemotherapy is one of the leading causes of death in clinical oncology.

This revolutionary new approach, called adaptive therapy, was tested in a pilot study on 17 patients with metastatic prostate cancer. (1).

Patients were treated with abiraterone, a testosterone-lowering drug, until PSA levels, a marker for prostate cancer, dropped by 50%, indicating a partial tumor response. Treatment was then stopped, allowing the cancer cells to begin growing again, but because the chemotherapy agent no longer exerts selective pressure, the recurrent tumor cell population is not particularly resistant to chemotherapy.

When PSA levels become high again, treatment is resumed to reduce them by 50% again, and this treatment/discontinuation cycle is repeated as many times as necessary to prevent cancer progression.

The results of the pilot study are very encouraging: compared with standard treatment using continuous chemotherapy, patients receiving the adaptive approach lived longer without cancer progression (33.5 vs 14.3 months) and showed a clear improvement in overall survival (58.5 vs 31. 3). months).

It should also be noted that all patients who received standard treatment experienced cancer progression during the study and died, while 4 patients who received adaptive therapy were still alive at the time of publication of the study.

Nearly 200 years after its discovery, evolution by natural selection remains essential to understanding life around us and the diseases that affect us. As is often said, great ideas never die.

Darwin’s genius continues to influence human evolution.

(1) Gatenby R.A. and others. Adaptive therapy. Cancer Res. 2009; 69:4894-903.
(2) Zhang J, et al. Evolution-based mathematical models significantly prolong response to abiraterone in metastatic castration-resistant prostate cancer and identify strategies to further improve outcomes. Life 2022;11:e76284.

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