Abstract PR03: Single-cell proteomic analysis of the tumoral heterogeneity in response to PARP inhibitor

Although poly (ADP-ribose) polymerase (PARP) inhibitors have shown efficacy in the treatment and maintenance of ovarian cancer patients, development of PARP inhibitor resistance is frequent. Our group and others have demonstrated that the cancer cells’ adaptive responses to PARP inhibitor can be detected at the protein level and targeting these adaptive responses increases the depth and duration of treatment and might prevent the development of drug resistance. However, it is still unclear if these adaptive responses are conserved across cancer cells from the same tumor and across cells from different lesions. Having a better understanding of the heterogeneity of adaptive responses might help develop better approaches of PARP-based combination therapies. The objective of this study was to develop a single-cell proteomic approach to investigate the heterogeneity of adaptive responses in ovarian cancer tumors. We developed a cyclic-immunofluorescence antibody panel and measured the expression of more than 40 proteins at the single-cell level in several ovarian cancer tumors that have been treated with PARP inhibitors. We also performed reverse-phased protein array (RPPA) analysis on protein extracted from the tumors and measured the activity of several pathways know to be altered in response to PARP inhibitors. Overall, our results demonstrated that adaptive responses can be detected at the single-cell level through cyclic immunofluorescence. Furthermore, although RPPA assays capture the main pathway alterations in response to PARP inhibitors, cyclic immunofluorescence adds complementary information by allowing a spatial-oriented analysis of the different cell populations as well as their frequency. Overall, this approach might lead to a better understanding of how cancer cells try to survive therapeutic stress and improve the decision-making process in the treatment of ovarian cancer patients. This abstract is also being presented as Poster A19. Citation Format: Nicholas D. Kendsersky, Hongli Ma, Yong Fang, Lydia G. Campbell, Jenny Eng, Sanghoon Lee, Koei Chin, Shannon N. Westin, Gordon B. Mills, Marilyne Labrie. Single-cell proteomic analysis of the tumoral heterogeneity in response to PARP inhibitor [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr PR03.