Hyper-Dependence on NHEJ Enables Synergy between DNA-PK Inhibitors and Low-Dose Doxorubicin in Leiomyosarcoma

Abstract

Combinations of DNA-PK inhibitors with unconventionally low, sensitizing, doxorubicin dosing showed synergistic effects in LMS in vitro and in vivo models, without discernable toxicity. These findings underscore the relevance of DNA damage repair alterations in LMS pathogenesis and identify dependence on NHEJ as a clinically actionable vulnerability in LMS.