Are CRISPR Screens Providing the Next Generation of Therapeutic Targets?

CRISPR screens combined with molecular and genetic profiling of large panels of cell lines are helping to systematically identify cancer vulnerabilities. These large-scale screens, together with focused in vivo and isogenic cell line screens, have identified a growing number of promising targets and led directly to numerous target-specific drug discovery programs, several of which have reached clinical testing. However, systematic loss-of-function studies are still in their early stages. Genetic redundancy, the limitation of cell line models for many cancer types, and the difficulty of conducting complex in vitro and in vivo screens remain opportunities for discovery. We expect that over the next few years, efforts like the Cancer Dependency Map along with more focused screens will play a significant role in the creation of a roadmap of oncology therapeutic targets. ©2021 American Association for Cancer Research.