Targeted Therapies

Part of the series Molecular and Translational Medicine pp 127-134


Somatic Evolution of Acquired Drug Resistance in Cancer

  • John W. PepperAffiliated withDivision of Cancer Prevention, National Cancer Institute Email author 

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Acquired drug resistance is a central problem in cancer medicine. The diverse molecular mechanisms of acquired drug resistance all arise through the same process of somatic (within-body) cellular evolution. Even targeted drugs are subject to this failure. Genetic instability causes high genetic diversity among the cells of most cancers, but because somatic evolution results from selection as well as mutation, some classes of therapies are less prone than others to failure through acquired resistance. Cytotoxins, whether targeted or not, are especially prone to acquired drug resistance. Among the most promising classes of therapies expected to be robust against acquired resistance are: those that target systemic cancer symptoms instead of cancer cells, those that target cell motility rather than survival and proliferation, and those that target secreted metabolites of cancer cells rather than the cells themselves.


Somatic evolution Clonal selection Systemic pathology Cell motility Public goods