Abstract
The Columbia Cancer Target Discovery and Development (CTD2) Center has developed PANACEA (PANcancer Analysis of Chemical Entity Activity), a collection of dose-response curves and perturbational profiles for 400 clinical oncology drugs in cell lines selected to optimally represent 19 cancer subtypes. This resource, developed to study tumor-specific drug mechanism of action, was instrumental in hosting a DREAM Challenge to assess computational models for de novo drug polypharmacology prediction. Dose-response and perturbational profiles for 32 kinase inhibitors were provided to 21 participating teams who were asked to predict high-affinity binding target among 255 possible protein kinases. Best performing methods leveraged both gene expression profile similarity analysis, and deep-learning methodologies trained on individual datasets. This study lays the foundation for future integrative analyses of pharmacogenomic data, reconciliation of polypharmacology effects in different tumor contexts, and insights into network-based assessment of context-specific drug mechanism of action.
Competing Interest Statement
A.C. is founder, equity holder, and consultant of DarwinHealth Inc., a company that has licensed the PANACEA database used in this manuscript from Columbia University. Columbia University is also an equity holder in DarwinHealth Inc. Other authors declare no conflicts of interest.
Footnotes
Author typo corrected.