Abstract GMM-023: PATIENT DERIVED XENOGRAFTS (PDXS) AND PDX DERIVED TUMOR CELLS (PDTC) ALLOW THE IDENTIFICATION OF ACTIONABLE CANCER GENES AND TREATMENT OPTIONS FOR PLATINUM REFRACTORY/RESISTANT OVARIAN CARCINOMAS

摘要: Patients with advanced ovarian cancers have experienced little improvement in overall survival standard treatments even after the incorporation of anti-angiogenic therapies. Besides anti-PARP inhibitors, matching individual critical genomic alterations best available drugs has not as other cancers, likely because a handful cancer-related genes are mutated at high frequency, while many more found much lower frequencies. This so called “mutation tail” is only long but also mostly unexplored. We used Patient Derived Xenografts (PDXs) to identify actionable cancer and PDX Tumor Cells (PDTCs) accelerate discovery treatment options. envisioned that alleged weakness models, i.e. lack human stromal immune cells, might be instrumental mutations test approved or experimental targeted monotherapy different combinations link biomarkers treatments. Forty-nine lines from metastatic epithelial carcinomas been propagated fully characterized far histology, immunohistochemistry high-grade serous-specific markers presence TP53 BRCA1/2 mutations. Copy number variations (CNV) analysis Whole Exome Sequencing (WES) were carried out derived naive carcinomas, which came refractory/resistant platinum drugs. studied non-synonymous allele frequencies ≥0.1. Only listed databases further analyzed. SNPdb allowed ruling polymorphisms. SIFT PROVEAN softwares predicted deleterious damaging effects onto protein sequences. DGIdb helped selecting genes. identified one line, possibly loss-of-function mutation PIK3R1 gene (encoding p85alpha regulatory subunit PI3K) had an frequency=0.9 early late passages. Moreover, two micro-dissected FFPE samples source tumor this frequency nearly identical TP53. Hence, PIK3R1W624R could trunk line counterpart. Treatment options assayed ex-vivo, on short-term cultures PDTCs line. Buparlisib, pan-class I PI3K inhibitor, showed ability block proliferation growth vivo PDXs regression preclinical trial. These data proofed-the-concept PDX-based pipeline able unveil pathways for advanced/metastatic cancer. Citation Format: Martina Olivero, Jessica Erriquez, Maddalena Arigoni, Sonia Capellero, Concetta D9Ambrosio, Gloria Mittica, Fulvio Borella, Dionyssios Katsaros, Silvana Privitera, Enrico Berrino, Tiziana Venesio, Giorgio Valabrega, Raffaele Calogero Maria Flavia Di Renzo. PATIENT DERIVED XENOGRAFTS (PDXS) AND TUMOR CELLS (PDTC) ALLOW THE IDENTIFICATION OF ACTIONABLE CANCER GENES TREATMENT OPTIONS FOR PLATINUM REFRACTORY/RESISTANT OVARIAN CARCINOMAS [abstract]. In: Proceedings 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Res 2019;25(22 Suppl):Abstract nr GMM-023.