Abstract 608: Comprehensive drug testing of patient-derived conditionally reprogrammed cells from castration-resistant prostate cancer

Abstract

Abstract Culture of human prostate cancer (PCa) progenitor cells would facilitate the discovery and testing of new, potentially curative therapies for PCa. Here, we established and characterized patient-derived conditionally reprogrammed cells (CRCs) from seven patients to determine their biological properties (genomic, transcriptomic, protein expression) and to apply these cells to test efficacies of 306 emerging and clinically approved drugs. The patient samples came from both primary prostate cancer as well as from advanced Castration-Resistant Prostate Cancer (CRPC). Patients with primary prostate cancer generated six benign CRC cultures which all had an androgen receptor (AR)-negative, basal/transit-amplifying phenotype with few CNAs. In 3D cell culture, these cells could re-express AR. The CRCs from a CRPC patient (HUB.5) displayed multiple CNAs, many of which were shared with the parental tumor. We carried out high-throughput drug-response studies with 306 emerging and clinical cancer drugs. Bcl-2 family inhibitor navitoclax emerged as the most potent cancer-specific drug for the CRCs from CRPC patient. Other drug efficacies observed included taxanes, mepacrine and retinoids, thus covering both existing (and clinically validated) as well as new drug efficacies. In conclusion, comprehensive cancer-pharmacopeia-wide drug testing of CRCs from a CRPC patient highlighted both known and novel drug sensitivities in PCa, including navitoclax, which is currently tested in clinical trials of CRPC. Citation Format: Khalid Saeed, Vesa Rahkama, Samuli Eldfors, Dmitrii Bychkov, John Patrick Mpindi, Bhagwan Yadav, Tero Aittokallio, Peter Horvath, Donna Peehl, Lassi Paavolainen, Caroline Heckman, Krister Wennerberg, Tuomas Mirtti, Antti Rannikko, Olli Kallioniemia, Päivi Östling, Taija af Hällström. Comprehensive drug testing of patient-derived conditionally reprogrammed cells from castration-resistant prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 608.