Synthetic Lethality-mediated Precision Oncology Via the Tumor Transcriptome

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2021 Apr 15

PMID 33857424

Citations 49

Authors

Joo Sang Lee

Nishanth Ulhas Nair

Gal Dinstag

Lesley Chapman

Youngmin Chung

Kun Wang

Sanju Sinha

Hongui Cha

Dasol Kim

Alexander V Schperberg

Ajay Srinivasan

Vladimir Lazar

Eitan Rubin

Sohyun Hwang

Raanan Berger

Tuvik Beker

Zeev Ronai

Sridhar Hannenhalli

Mark R Gilbert

Razelle Kurzrock

Se-Hoon Lee

Kenneth Aldape

Eytan Ruppin

Affiliations

Soon will be listed here.

Abstract

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.

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