Abstract A163: The combined treatment modality of a hypoxia-activated prodrug (Evofosfamide) with ionizing radiation

Hypoxia is a hallmark of many solid malignancies and confers resistance to radiotherapy as well as other treatment regimens. We investigated the combined treatment modality of ionizing radiation (IR) with the clinical stage hypoxia-activated prodrug (HAP; evofosfamide) in vitro and in vivo using mechanistic and efficacy-oriented endpoints. Based on the current insights, the combined treatment modality of IR with this HAP might lead to complementary tumor cell killing. Ionizing radiation will primarily target well-oxygenated tumor cells, while the HAP will primarily kill hypoxic tumor cells. At the same time enhanced, supra-additive cytotoxicity will be expected by the diffusible activated prodrug leading to more complex DNA damage when used in combination with IR. METHODS We investigated the cytotoxic effects of evofosfamide on tumor cell (A549 lung carcinoma and UT-SCC-14 headn 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A163.