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

In this issue of Cancer Research, Liang and colleagues perform a genome-wide CRISPR-Cas9-negative loss-of-function screen and identify WEE1 kinase as a therapeutic vulnerability in cells depleted of the ATRX 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.See related article by Liang et al., p. 510.