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Abstract 1164: Pdx model of pleural effusion of lung cancer patient for testing on targeted drug sensitivity and resistance

Advanced lung cancer of late stage patients is selectively sensitive to available targeted therapeutics and often develops resistance to early sensitive drug treatment. Surgery tumor tissues are usually not available to establish patient-derived xenograft (PDX) models which is critical to evaluate drug sensitivity and resistance. We applied CD45 magnet beads to enrich the tumor cell population from pleural effusion specimens of advanced lung cancer. Valuable drug-resistant PDX models were successfully established both from pleural effusion and from routine surgery tissues. Genetic profiling of the PDX models revealed TKI drug-associated EGFR mutations (L858R, T790M, Exon19del, C797S). In particular we successfully established a clinically AZD9291-resistant EGFR triple mutant (Ex19del, T790M, C797S) PDX model. In vivo efficacy results with gefitinib, erlotinib and AZD9291 well matched corresponding gene mutations among the models. Interestingly, we successfully induced AZD9291-resistant clones in vivo using an EGFR double mutant (L858R, T790M) PDX model, and NGS revealed mutations in kinases involved in other signaling pathways, indicating potential therapeutic options against resistance emergence. In conclusion, these precious PDX models provide insight into resistance mechanisms as well as serve as models to test potency of many drugs including current investigational TKIs. Citation Format: Feifei Zhang, Zhen Zhou, Yuan Long, Wenhua Xu, Shizhu Zhao, Yang Yang, Hui Liu, Jijun Cheng, Shun Lu, Danyi Wen. Pdx model of pleural effusion of lung cancer patient for testing on targeted drug sensitivity and resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1164.