Drug-adapted cancer cell lines as preclinical models of acquired resistance

Acquired resistance formation limits the efficacy of anti-cancer therapies.Acquired and intrinsic resistance differ conceptually.Acquired resistance is the consequence of directed evolution,whereas intrinsic resistance depends on the(stochastic)presence of pre-existing resistance mechanisms.Preclinical model systems are needed to study acquired drug resistance because they enable:(1)in depth functional studies;(2)the investigation of non-standard treatments for a certain disease condition(which is necessary to identify small groups of responders);and(3)the comparison of multiple therapies in the same system.Hence,they complement data derived from clinical trials and clinical specimens,including liquid biopsies.Many groups have successfully used drug-adapted cancer cell lines to identify and elucidate clinically relevant resistance mechanisms to targeted and cytotoxic anti-cancer drugs.Hence,we argue that drug-adapted cancer cell lines represent a preclinical model system in their own right that is complementary to other preclinical model systems and clinical data.