Tepeli, Y. I.; Trastulla, L.; Goncalves, J. P.; Iorio, F.

Oncogenes, when mutated or overexpressed, drive tumorigenesis and can lead to oncogene addiction, where cancer cells rely on such genes for survival and proliferation. Stratifying oncogene-addicted cohorts is essential to uncover alternative therapeutic avenues, for instance in cases of untargetable oncogenes or resistance to treatment. We propose Oncostratifier, a framework to identify drugs that specifically target oncogene-addicted cancer cohorts, differentiating between drugs that induce sensitivity or resistance. Our results reveal 21,020 stratifying drugs spanning 267 oncogenes in cell lines of 31 different cancer types. We identify 59 mutational markers associated with 36 of the stratifying drugs, which can possibly be used to stratify patient tumors in the absence of drug response data. These findings reveal the potential of Oncostratifier as a tool to generate candidate hypotheses for precision cancer treatment strategies. Explore our detailed results at https://edu.nl/6hnct