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

CONCLUSION: 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.PMID:37773632 | DOI:10.1158/1078-0432.CCR-23-0998

Source: Clinical Cancer Research - September 29, 2023 Category: Cancer & Oncology Authors: Adri án Mariño-Enríquez Jan Philipp Novotny Doga C Gulhan Isabella Klooster Antuan V Tran Macy Kasbo Meijun Z Lundberg Wen-Bin Ou Derrick L Tao Daniel F Pilco-Janeta Victor Y Mao Frank T Zenke Brittaney A Leeper Prafulla C Gokhale Glenn S Cowley Lauren Source Type: research