Abstract 13: Individualized approach for ovarian cancer: Identification of potential therapeutic targets based on genomic analyses, testing efficiency of treatments, and monitoring

Ovarian cancer (OCa) is fifth leading cause of death among women. Most of OCa patients diagnosed with high stage invasive disease. Although, majority experience remission after surgical debulking and adjuvant chemotherapy, about 80% of patients relapse and/or develop chemoresistant disease. More efficient diagnostics and therapies are needed to improve outcome in ovarian cancer. We used an integrated approach to characterize genomic rearrangements in serous OCa inordet to identify potentially targetable alterations and test treatments with corresponding drugs using matching mouse avatar models. Mate-pair next generation sequencing protocol and BIMA2 algorithm were used to identify chromosomal rearrangements, including gene fusions and copy number changes, in primary tumors. Further analysis was then performed to determine alterations that may also be therapeutically targeted. Total of 25 primary tumors were analyzed, out of which four were selected for genomically guided treatments in corresponding mouse avatars. The tumors propagated in the selected mouse lines were also sequenced and showed identical to original patient tumor landscape of rearrangements. In addition, the selected targetable alterations were validated in both patient and avatar tumor DNA. For several of the analyzed cases pre-surgical and postsurgical blood was available for detection of selected alterations in cell free circulating tumor DNA. The analysis revealed presence of selected rearrangements in pre-surgical blood of all tested cases and in a number of those that showed presence of the disease after surgery. In summary, we showed that the whole genome sequencing of DNA rearrangements in conjunction with analyses of therapeutic targets and treatment testing in mouse avatars, developed using primary tumors, is a promising approach to aid treatment decisions for individual ovarian cancer patients. Note: This abstract was not presented at the conference. Citation Format: Faye R. Harris, Geoffrey C. Halling, Marc A. Becker, Paul Haluska, Jr., George Vasmatzis, Irina V. Kovtun. Individualized approach for ovarian cancer: Identification of potential therapeutic targets based on genomic analyses, testing efficiency of treatments, and monitoring. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 13.