Moving beyond PARP Inhibition in ATM-Deficient Prostate Cancer.

Abstract

DNA repair defects are found in primary and metastatic prostate cancer. Alterations in the <i>ATM</i> gene are the second most common defect after <i>BRCA2</i>, but their sensitivity to PARP inhibitors has been questioned by recent clinical literature. The work by Rafiei and colleagues in this issue of <i>Cancer Research</i> now supports this observation with genetically engineered cells and quantitative responses. ATR inhibitors have not yet found a clear role in the clinic, but the new work suggests that ATM-deficient cancers may be more vulnerable to ATR inhibition rather than PARP inhibitors, which is a testable hypothesis for clinical trials.<i>See related article by Rafiei et al., p. 2094</i>.