Treating cancers with high doses of tumor-targeting drugs often triggers the evolution of drug resistance, which leads to tumor progression. Researchers are consequently exploring alternative treatment strategies that manipulate tumor evolution to a patient’s advantage—by exploiting drug resistance instead of trying to avoid it.
Evolutionary Dead End
Clinicians administer a drug and thus select for cells with resistance-conferring mutations. Then, having narrowed the population down to just those resistant cells, they administer a second drug designed to target a weakness, what researchers refer to as a “collateral sensitivity,” in those same cells.
Researchers administer low levels of a drug, enough to kill most, but not all, of the vulnerable cells in the tumor population while favoring the survival of drug-resistant lineages. Once the tumor has shrunk, clinicians stop administering the drug. The drug-sensitive cells, which tend to have a competitive edge over cells that have invested in a costly drug-resistance mechanism, can now begin to grow back. Competition between drug-sensitive and drug-resistant cells for resources in the tumor microenvironment keeps the tumor size in check.
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