Abstract B30: Talazoparib efficacy is enhanced by noncytotoxic doses of temozolomide-mediated DNA damage in prostate cancer cell lines

Conclusion: Talazoparib is cytotoxic to prostate cancer cells as a single agent in nonclinical cell based models. Herein, we demonstrate that combining noncytotoxic doses of TMZ with talazoparib improves efficacy in killing of LNCaP and 22RV1 cells. The increased efficacy corresponds with increased DNA-damage and increased trapped PARP-DNA complexes. Low, noncytotoxic doses of TMZ are shown to generate DNA damage sites in vitro and in treated LNCaP cells, providing a mechanistic basis for the combination effect of talazoparib and TMZ. Together, these nonclinical data provide scientific rationale for a clinical trial strategy of combining talazoparib with low, noncytotoxic doses of TMZ to enhance efficacy in prostate cancer.Citation Format: Jeffrey N. Lindquist, Vernon T. Phan, Eduardo Riquelme, Kakoli Mukherjee, Olivia Farías, Ashu Gupta, Mohd Raja, Roopa Rai, Hirdesh Uppal, Andrew A. Protter. Talazoparib efficacy is enhanced by noncytotoxic doses of temozolomide-mediated DNA damage in prostate cancer cell lines [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr B30.

Source: Molecular Cancer Research - April 2, 2017 Category: Cancer & Oncology Authors: Lindquist, J. N., Phan, V. T., Riquelme, E., Mukherjee, K., Farias, O., Gupta, A., Raja, M., Rai, R., Uppal, H., Protter, A. A. Tags: Therapies Targeting Checkpoints and Mismatch Repair: Poster Presentations - Proffered Abstracts Source Type: research