Abstract 66: High-throughput screening using patient derived tumor cell to conduct personalized medicine

Abstract

Abstract Background: Patient-derived cell (PDC) model is one of prospective technologies to investigate drug response for precision medicine. Previously drug sensitivity derived PDC model has been studied in colorectal cancer organoid culture or lung cancer model. They revealed that PDC model recapitulates genomic characteristic and drug high-throughput screening is amenable. We established PDC models from metastatic cancer cohort of multiple cancer types, and revealed genomic characteristics and matched drug response. Method: Target sequencing was performed using OncoPanel. We called SNV, and CNV from target sequencing using GATK, then clinically unassociated SNPs were eliminated. Somatic submodules were identified from integrative variant profiles using HotNet referring HPRD. Drug high-throughput screening was performed SEMCO platform. In order to identify sensitive drug and variant gene pairs, drug sensitivity was tested by ANOVA using IC50 values. Result: Target sequencing of exome were generated from our 165 PDC models, and drug high-throughput screening was performed from 30 PDCs and ant-cancer 15 drugs. We tried integrative analysis approaches from genomic profile including mutation and copy number alteration, and identified genomic modules related with Fanconi, Hedgehog, FGFR receptor, Cytokine-cytokine receptor pathway. Variants of known oncogenes were successfully identified in MET, BRAF, FGFR and PIK4CA. Especially novel and recurrent mutations were identified in FGFR2, and corresponding samples indicated AZD4547 sensitivity as well as known drug response case such as BRAF V600E targeting Vemurafenib. Conclusion: Our study explains that PDC cohort sustains cancer related pathways, and its drug response follows genomic features. It is expected that our research would contribute to facilitate precision medicine from PDC model to utilize genomics and drug response. Citation Format: Seung T. Kim, Charny Park, Sun Kim, Won Lee, Joon Park, Kyoung-Mee Kim, Woongyang Park, Jeeyun Lee, young park, Jiryeon Jang. High-throughput screening using patient derived tumor cell to conduct personalized medicine. [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 66.