Cell 154, 1151–1161 (2013)

Matching a genetically defined cancer cell line (CCL) with a specific drug to elicit optimal growth inhibition is often a good indicator for future clinical efficacy. Although current genetically matched therapies target oncogenes themselves, targeting genes that cooperate with oncogenes to ensure survival and proliferation (oncogene-induced dependencies) may potentially form the basis for additional effective therapies. To identify these dependencies, Basu et al. embarked on a large-scale analysis measuring the cell growth of 242 characterized CCLs in response to a set of 354 well-annotated small molecules. These findings were translated into an online portal called the Cancer Therapeutics Response Portal (CTRP) (http://www.broadinstitute.org/ctrp/), which contains more than 70,000 connections between drug sensitivities and the genetic features of CCLs. This resource was successful in identifying common features in particular groups of CCLs that were either responsive or unresponsive to a particular drug, creating potential new therapies. For example, CCLs containing activating mutations in β-catenin (CTNNB1) exhibited strong sensitivity in response to the Bcl-2 family antagonist navitoclax. The data set also identified compounds with strong potency for specific lineages; for example, RSL3 and related probes for ferroptosis potently caused cell death in a group of ovarian CCLs. Thus, the CTRP, which will be updated with additional data in the future, can assist researchers in developing new drugs and combinations to improve cancer therapy.