Resistance to targeted therapy



Resistance to systemic therapy is the main factor that leads to patients death. The appearance of resistance is caused by genetic and phenotypic heterogeneity of tumor cells. In turn heterogeneity is caused by genetic instability that drive tumor evolution under the pressure of neutral or selective factors. Contemporary drugs execute various molecules as a targets of antitumor activity, their blockage leads to disruption in tumor metabolism and sometimes to cell death. Theoretical and practical efficacy of the drug is in proportion to the share of cells for which particular mechanism that is targeted by the drug is vulnerable. Contemporary drugs use various intracellular molecules as a target of their anticancer activity. Their blockade results in disruption of metabolic or growth cascades in tumor cells and may lead to cell death. Obviously, theoretical and practical efficacy of the drug is in direct proportion to the amount of cells that are vulnerable to the blockade of particular pathway, and is indirectly proportional to the share of cells that have «shunting» mechanisms.

In this review article authors discuss the available data on the origin of resistance using as an example EGFR mutated non-small cell lung cancer.