Investigating New Mechanisms of Acquired Resistance to Targeted Therapies: If You Hit Them Harder, Do They Get Up Differently?

Targeted therapies have revolutionized treatment of several different types of cancers. However, in almost an invariable fashion, cancers eventually regrow in the presence of the targeted therapy, a phenomenon referred to as acquired resistance. In this issue of Cancer Research, Finn and colleagues demonstrate that modeling acquired resistance to MET tyrosine kinase inhibition in a MET-amplified gastric cancer cell line by a single, high exposure of the targeted therapy reveals clinically relevant acquired resistant mechanisms, which may be more faithful and comprehensive than the ones revealed through traditional ramp-up approaches. See related article by Finn et al., p. 79