DR-383 Drug resistance in cancer from in vitro genetic screens

Drug resistance is a major limitation to the long-term efficacy of cancer drugs. The use of cancer genome sequencing has been used to understand genetic mechanisms of acquired resistance, but this is a retrospective approach and can take years to accrue sufficient sample numbers from post-treatment biopsies to infer cancer variant function. In our study, we have used high-throughput CRISPR mutagenesis screens of drug targets in cancer to predict genetic mechanisms of acquired drug resistance. We want to use the HMF data to validate our in vitro findings and validate our prediction model with patient data. The use of our prospective map of drug resistance variants could inform patient stratification for effective second-line therapies in cancer.

Matthew Coelho, Wellcome Sanger Institute, Cambridgeshire, United Kingdom