Abstract 473: PRKRA/PACT expression promotes chemoresistance in mucinous ovarian cancer

Purpose: To investigate the mechanisms of chemotherapy resistance and developing strategies to enhance therapeutic responses in mucinous ovarian cancer (MOC). Experimental design: We carried out a kinome-based siRNA screen using human MOC to identify novel targets to enhance the efficacy of chemotherapy in MOC cell lines. In vitro and in vivo validation studies were carried out using MOC models. We specifically interrogated the role of PRKRA in MOC based on our screen results. Results: Among the 939 genes in the screen, we focused on PRKRA/PACT because it was one of the top 5 target genes that exhibited the greatest extent of synthetic lethality in the target gene-siRNA plus oxaliplatin group relative to the target gene-siRNA group. The combination of oxaliplatin plus siPRKRA treatment resulted in significantly reduced cell viability compared with oxaliplatin plus control siRNA in RMUG-L-ip1 or RMUG-S-ip1 MOC cells (p Conclusion: The PRKRA/PACT axis represents an important therapeutic opportunity in MOC for enhancing oxaliplatin efficacy. Citation Format: Takeshi Hisamatsu, Michael McGuire, Sherry Y. Wu, Rajesha Rupaimoole, Sunila Pradeep, Kyunghee Noh, Justyna Filant, Jean M. Hansen, Yasmin Lyons, Kshipra M. Gharpure, Archana S. Nagaraja, Lingegowda S. Mangala, Takashi Mitamura, Cristian Rodriguez-Aguayo, Geoffrey A. Bartholomeusz, Cristina Ivan, Ju-Seong Lee, Koji Matsuo, Michael Frumovitz, Kwong K. Wong, Gabriel Lopez-Berestein, Anil K. Sood. PRKRA/PACT expression promotes chemoresistance in mucinous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 473. doi:10.1158/1538-7445.AM2017-473