Abstract B48: Prostate cancer pre-treatment with nanoformulated Olaparib overcomes radiation resistance

Abstracts: AACR Special Conference: Engineering and Physical Sciences in Oncology; June 25-28, 2016; Boston, MA Prostate cancers with PTEN deletions are promising candidates for DNA repair inhibitors such as olaparib and talazoparib. Here we show that radiation-resistant cells and tumors derived from Ptenpc-/-;Trp53pc-/- mice are rendered radiation-sensitive following pre-treatment with liposomal nanoOlaparib. This enhancement in radiosensitivity is accompanied by radiation dose-dependent changes in γ-H2AX expression and is specific to nanoformulated Olaparib alone. In animals, twice-weekly intravenous administration of nanoOlaparib alone results in significant tumor growth inhibition. When nanoOlaparib is administered prior to radiation, we find that a single dose of radiation is sufficient to increase mouse survival time by as much as 10 weeks (study duration = 13 weeks). Using ferumoxytol as a surrogate nanoparticle, magnetic resonance imaging (MRI) studies revealed that nanoOlaparib administration enhances the ability of nanoparticles to accumulate in tumors. Compared to untreated and radiation-only controls, nanoOlaparib-treated tumors showed 18-fold higher nanoparticle accumulation, suggesting that the in vivo efficacy of nanoOlaparib may be potentiated by its ability to enhance its own accumulation in tumors. Citation Format: Anne L. van de Ven, Shifalika Tangutoori, Paige Baldwin, Ju Qiao, Codi Gharagouzloo, Nina Seitzer, John Clohessy, Houari Korideck, G. Mike Makrigiorgos, Robert Cormack, Pier Paolo Pandolfi, Srinivas Sridhar. Prostate cancer pre-treatment with nanoformulated Olaparib overcomes radiation resistance. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B48.