Synthetic lethality-mediated precision oncology via the tumor transcriptome

Precision oncology has made significant advances, mainly by targeting actionable mutations in cancer driver genes. Aiming to expand treatment opportunities, recent studies have begun to explore the utility of tumor transcriptome to guide patient treatment. Here, we introduce SELECT (synthetic lethality and rescue-mediated precision oncology via the transcriptome), a precision oncology framework harnessing genetic interactions to predict patient response to cancer therapy from the tumor transcriptome. SELECT is tested on a broad collection of 35 published targeted and immunotherapy clinical trials from 10 different cancer types. It is predictive of patients' response in 80% of these clinical trials and in the recent multi-arm WINTHER trial. The predictive signatures and the code are made publicly available for academic use, laying a basis for future prospective clinical studies.

Automated summary

Precision oncology has advanced significantly by targeting actionable mutations in cancer driver genes and exploring the utility of tumor transcriptome to guide patient treatment. SELECT, a precision oncology framework harnessing genetic interactions, has shown predictive accuracy in 80% of tested clinical trials and is publicly available for academic use, providing a foundation for future prospective clinical studies.