H3 Biomedicine 1 article published in JoVE Medicine Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms Manav Korpal1, Jacob Feala1, Xiaoling Puyang1, Jian Zou1, Alex H. Ramos2, Jeremy Wu1, Timm Baumeister1, Lihua Yu1, Markus Warmuth1, Ping Zhu1 1H3 Biomedicine, 2Massachusetts General Hospital Drug resistance to targeted therapeutics is widespread and the need to identify mechanisms of resistance--prior to or following clinical onset--is critical for guiding alternative clinical management strategies. Here, we present a protocol to couple derivation of drug-resistant lines in vitro with sequencing to expedite discovery of these mechanisms.