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- W4285588227 abstract "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 radiosensitization was also obtained using KP167 and AQ4N in 2D normoxia. Although hypoxia induced radioresistance, radiosensitization by KP167 was still greater under 2D hypoxia, yielding SER 0.01 of 1.56–2.37 compared with AQ4N SER 0.01 of 1.13–1.94. Such data show KP167 as a promising single agent and potent radiosensitiser of both normoxic and hypoxic breast cancer cells, with greater efficacy in TNBCs." @default.
- W4285588227 created "2022-07-16" @default.
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- W4285588227 date "2022-07-16" @default.
- W4285588227 modified "2023-09-27" @default.
- W4285588227 title "In vitro radiosensitization of breast cancer with hypoxia‐activated prodrugs" @default.
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- W4285588227 doi "https://doi.org/10.1111/jcmm.17486" @default.
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