CRISPR screens and data integration to prioritise new therapeutic targets in cancer
Speaker: Dr Francesco Iorio, Principal Staff Scientist, Cancer Dependency Map Analytics Team Leader. Cancer, Ageing and Somatic Mutation. Wellcome Trust Sanger Institute (Cambridge, UK).
Organizers: IRB Barcelona
Date: Friday 20 September, 12.00h
Place: Felix Serratosa Hall, Parc Cientific de Barcelona
Host: Patrick Aloy, PhD - IRB Barcelona
Functional genomics approaches can overcome limitations that hamper oncology drug development such as lack of robust target identification and poor clinical efficacy. We performed genome-scale CRISPR-Cas9 screens in 324 human cancer cell lines from 30 cancer types and developed a data-driven framework to prioritise cancer therapeutic candidates. We integrated cell fitness effects with genomic biomarkers and target tractability for drug development to systematically prioritise new targets in defined tissues and genotypes. We verified one of our most promising dependencies, Werner syndrome ATP-dependent helicase, as a synthetic-lethal target in tumours from multiple cancer types with microsatellite instability. Our analysis provides a comprehensive resource of cancer dependencies, generates a framework to prioritise oncology targets, and nominates specific new targets. The principles described in this study can inform the initial stages of drug development by contributing a new, diverse and more effective portfolio of oncology targets.