Abstract A02: Expanding tumor chemical-genetic interaction map using next-generation cancer models

• DOI: 10.1158/1538-8514.synthleth-a02
• Publication Date: 2017-12-01T14:38:58Z
• Authors: Yuen-Yi (Moony) T...; Andrew Hong; Shubhroz Gill; Paula Keskula; Srivatsan Raghavan; Jaime Cheah; Aviad Tsherniak; Francisca Vazquez; Sahar Alkhairy; Anson Peng; Abeer Sayeed; Rebecca Deasy; Peter Ronning; Philip Kantoff; Levi Garraway; Mark Rubin; Calvin Kuo; Sidharth Puram; Adi Gazdar; Nikhil Wagle; Adam Bass; Keith Ligon; Katherine Janeway; David Root; Stuart Schreiber; Paul Clemons; Todd Golub; William Hahn; Jesse Boehm
• Keywords: Health informatics tools; Pediatric cancer

Abstract The development of new cancer therapeutics requires sufficient genetic and phenotypic diversity models. Current collections human cell lines are limited for many rare types, zero models exist that broadly available. Here, we report results from the pilot phase Cancer Cell Line Factory (CCLF) project aims to overcome this obstacle by systematically creating next-generation in vitro adult pediatric patients' specimens making these We first developed a workflow laboratory, genomics informatics tools make it possible compare published ex vivo culture conditions each individual tumor enable scientific community iterate towards disease-specific recipes. Based on sample volume rarity, 4-100 were applied all data was captured custom Laboratory Information Management System enhance subsequent predictions. $150, 5-day turnaround panel validate cultures based genomics. Importantly, show can be retained such patient-derived generally stable across 20 passages. Since inception project, have processed over 600 patient 450 patients 16 types successful generation 100 genomically characterized normal next hypothesized novel could used dependency To do so, tested 72 against informer set 440 compounds Broad Target Discovery Development (CTD2) Center. generating testing their sensitivities within 3 months is feasible high-throughput drug responses reproducible. Moreover, strengthen relationships between cellular features, compared with recently identical 860 existing lines. With approach, chemical-genetic interaction vulnerabilities rapidly assessed. adding more dimensions quantity increases predictive power map. currently evaluating sensitivity predictors co-dependencies. Overall, our proof-of-concept framework demonstrates initial feasibility at scale expanding map identify vulnerability. Citation Format: Yuen-Yi (Moony) Tseng, Andrew Hong, Shubhroz Gill, Paula Keskula, Srivatsan Raghavan, Jaime Cheah, Aviad Tsherniak, Francisca Vazquez, Sahar Alkhairy, Anson Peng, Abeer Sayeed, Rebecca Deasy, Peter Ronning, Philip Kantoff, Levi Garraway, Mark Rubin, Calvin Kuo, Sidharth Puram, Adi Gazdar, Nikhil Wagle, Adam Bass, Keith Ligon, Katherine Janeway, David Root, Stuart Schreiber, Paul Clemons, Todd Golub, William Hahn, Jesse Boehm. Expanding using [abstract]. In: Proceedings AACR Precision Medicine Series: Opportunities Challenges Exploiting Synthetic Lethality Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Ther 2017;16(10 Suppl):Abstract nr A02.