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.
Korpal, M., Feala, J., Puyang, X., Zou, J., Ramos, A. H., Wu, J., Baumeister, T., Yu, L., Warmuth, M., Zhu, P. Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms. J. Vis. Exp. (106), e52879, doi:10.3791/52879 (2015).