Synthetic lethality-mediated precision oncology via the tumor transcriptome. Cell 2021 Apr 29;184(9):2487-2502.e13
Date
04/16/2021Pubmed ID
33857424Pubmed Central ID
PMC9310669DOI
10.1016/j.cell.2021.03.030Scopus ID
2-s2.0-85104146184 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
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.
Author List
Lee JS, Nair NU, Dinstag G, Chapman L, Chung Y, Wang K, Sinha S, Cha H, Kim D, Schperberg AV, Srinivasan A, Lazar V, Rubin E, Hwang S, Berger R, Beker T, Ronai Z, Hannenhalli S, Gilbert MR, Kurzrock R, Lee SH, Aldape K, Ruppin EAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedBiomarkers, Tumor
Clinical Trials as Topic
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Immunotherapy
Male
Molecular Targeted Therapy
Neoplasms
Precision Medicine
Prognosis
Prospective Studies
Retrospective Studies
Survival Rate
Synthetic Lethal Mutations
Transcriptome
