Abstract 436: Enhanced induction of apoptosis by PLK1 inhibition and radiation is associated with the additive, but not supra-additive, killing effect of the combined treatment.

Chemoradiotherapy has been employed to improve the clinical outcomes of cancer patients. The rationale for the combined usage of chemotherapeutics and radiation is the benefits of the additive or synergistic (supra-additive) effect of the two agents, leading to better treatment efficacy. Recent studies have shown that inhibition of Polo-like kinase1 (PLK1) function can sensitize head-and-neck squamous cell carcinoma and medulloblastoma cells to radiation. PLK1 is an important regulator of mitotic functions that is over-expressed in many cancers. It also plays a role in DNA double-strand break repair through phosphorylation of Rad51 recombinase. Therefore, PLK1 presents as an attractive target and we set out to determine if PLK1 inhibition can be used as a general strategy for radiosensitization. The half-maximal inhibitory concentrations (IC 50 ) of the PLK1 inhibitor BI2536 were first determined for various cancer cell lines as indicators of sensitivity using XTT assay. The IC 50 values of six different cancer (breast, lungs, pancreas, and colon) cell lines were Citation Format: Nelson Wong, Ripen Misri, Mohamed Khan. Enhanced induction of apoptosis by PLK1 inhibition and radiation is associated with the additive, but not supra-additive, killing effect of the combined treatment. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 436. doi:10.1158/1538-7445.AM2013-436