Targeting ATRX Loss through Inhibition of the Cell-Cycle Checkpoint Mediator WEE1.

Abstract

In this issue of <i>Cancer Research</i>, Liang and colleagues perform a genome-wide CRISPR-Cas9-negative loss-of-function screen and identify <i>WEE1</i> kinase as a therapeutic vulnerability in cells depleted of the <i>ATRX</i> chromatin remodeler gene. Because ATRX mutations are frequently mutated across a variety of pediatric and adult malignancies, this work may contribute to the preclinical rationale for a precision medicine trial of the WEE1 inhibitor AZD1775 (adavosertib) for patients whose tumors demonstrate ATRX loss.<i>See related article by Liang et al., p. 510</i>.