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Imagine that you are a firefighter trying to prevent a house from burning completely. After many hours of hard work, you saved the family, saved your pet's chinchilla and extinguished every visible embers – a job well done.
Would not it be strange if the fire comes back the next day? At first, you might think that little Johnny did not learn the lesson about games, but you realize that something strange is happening. Not only does this new fire burn hotter and spread faster than the previous day, but it also does not matter if you soak it in torrents of water.
In oncology, this type of scenario is extremely common. Cancer breeds so often that we forget how strange and unique this phenomenon is. no one complains that their flu case is "back" after six months or that their broken leg has "recurred". And when the cancer recurs, it sometimes does so in a form that does not respond to the treatments that had previously sent it. discount. It can even appear in an organ previously without cancer1.
In case of relapse, it is very likely that all the original cancer cells were not extinct. Even a handful of cells that remain after the first cycle of treatment can turn into a full-blown disease faster than expected.
To demonstrate how dramatic this may be, consider a single surviving cancer cell that divides once a day into two identical copies (which also divide once a day, etc.). We would have more than a hundred cells after one week, but the population would exceed one billion people after one month and, after two months, it would exceed one billion billion (more a quarter of a billion). The average human body contains only tens of billions of cells, this model of exponential growth does not explain perfectly the behavior of cancer.2but it shows that even undetectable levels of cancer can pose a threat.
It is not surprising that the cancer is growing rapidly, but it is a little more disconcerting that a chemical attack of several weeks can leave survivors – if it kills> 99.99% of the targeted cells, why not? does he not occupy the rest? And when a tumor comes back, why does not it sometimes react to the drugs that worked the first time?
The answers to both questions are buried in the cancer genome. As I explained earlier, tumors are often heterogeneous mosaics with many types of cells, each containing its own set of genetic mutations. Some of these mutations protect cells from cancer treatments and allow them to survive deadly bombardments3. When the bombardment is complete, only the drug-resistant cells are left to grow and divide. Therefore, the recurrent tumor will be entirely composed of cells that can not be touched by the therapeutic strategy that had worked so well before – in essence, the drug was selected for hard-to-kill cancer cells.
To combat this rapidly evolving enemy, pharmaceutical companies have invented drugs designed to exploit the weaknesses that the newly constructed defenses of cancer have not yet addressed. Back to our firefighter scene since the beginning of the article, this amounts to dropping your fire hose and picking up a carbon dioxide extinguisher. Cancer will sometimes resist second- and third-line therapies, but any success will give the patient extra valuable time.
Some drugs tend to be more effective against recurrent cancers. Immunotherapies against cancer4for example, release the power of the human immune system to identify and destroy cancer cells. Because relapsed cancers often contain many genetic mutations, the immune system is more likely to recognize them as invaders different from the rest of the body.
Tumor Heterogeneity, Exponential Growth, Drug Resistance – Doctors will continue to struggle with these fundamental interrelated aspects of cancer biology for the rest of human history. Let's build an arsenal that has the no less heterogeneous capabilities of a Swiss army knife instead of investing in the miracle solution. We may not be able to kill a werewolf or a vampire, but we will remain totally anchored in the awesome bbadities of reality.
Remarks
(1) This situation is different from the formation of a second tumor that has nothing to do with the first one. Although it may seem unlucky to suffer from two distinct cancers during a single life, the alternative scenario – the spread of cancer cells to another part of the body – is probably indicative of an illness. aggressive and with a darker overall prognosis.
(2) It wrongly badumes, for example, that no cell dies, continually divides, or does not change the rate of division.
(3) Cancer cells can acquire these resistance mutations either before (intrinsic resistance) or during treatment (acquired resistance). However, the time at which the mutation was acquired is often less important than the exact molecular mechanism by which it confers drug resistance.
(4) What earned James Allison and Tasuku Honjo the Nobel Prize in 2018.
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