ERG inhibition selectively sensitizes ERG-positive prostate cancer to radiation through DNA repair vulnerabilities and enhances response to androgen receptor inhibitors

Background

ERG overexpression, driven by TMPRSS2-ERG gene fusion, occurs in ~ 50% of prostate cancers (PCa) and defines a molecular subtype with distinct therapeutic vulnerabilities. Radiotherapy (RT) is a cornerstone for localized and locally advanced PCa, yet substantial number of patients experience treatment failure. This study investigates whether direct ERG inhibition selectively impairs the resolution of DNA damage signaling and radiosensitizes ERG-positive PCa, providing a precision medicine strategy.