In vitro radiosensitization of breast cancer with hypoxia-activated prodrugs.

ABSTRACT: KP167 is a novel hypoxia-activated prodrug (HAP), targeting cancer cells via DNA intercalating and alkylating properties. The single agent and radiosensitizing efficacy of KP167 and its parental comparator, AQ4N, were evaluated in 2D and 3D cultures of luminal and triple negative breast cancer (TNBC) cell lines and compared against DNA damage repair inhibitors. 2D normoxic treatment with the DNA repair inhibitors, Olaparib or KU-55933 caused, as expected, substantial radiosensitization (sensitiser enhancement ratio, SER_0.01 of 1.60-3.42). KP167 induced greater radiosensitization in TNBC (SER_0.01 2.53 in MDAMB-231, 2.28 in MDAMB-468, 4.55 in MDAMB-436) and luminal spheroids (SER_0.01 1.46 in MCF-7 and 1.76 in T47D cells) compared with AQ4N. Significant radios

SUBMITTER: Aiyappa-Maudsley R 

PROVIDER: S-EPMC9357624 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature