Abstract A36: Establishment of patient-derived xenograft models of lung adenocarcinoma with two different EGFR mutations, L858R and exon19 deletion

Abstract

Abstract Preclinical tumor models that resemble the characteristics of patients’ tumors are essential for development of novel therapy. Patient-derived tumor xenograft (PDX) models are considered to be interesting candidates. However, success rate of PDX models of lung cancer, especially adenocarcinoma, is much lower than that of other types of tumors, including colon cancer. This study was conducted to establish clinically relevant PDX models of lung cancer. We obtained fresh surgically resected specimens from 20 NSCLC patients (10 squamous cell carcinomas, 9 adenocarcinomas, and 1 large cell carcinoma) who had submitted the written informed consent for this study, which was performed in accordance with protocols approved by the IRB of Kanazawa University. We inoculated the tumor fragments subcutaneously into immunodeficient mice, NOG mice or SCID hairless outbred (SHO) mice. The tumor take rate was 40% (8/20), with higher rates for squamous cell carcinoma (60%, 6/10) than for adenocarcinoma (22%, 2/9). Interestingly, both of two adenocarcinomas that successfully developed PDX tumors had EGFR mutations, L858R and exon 19 deletion, respectively. These PDX tumors maintained histology of adenocarcinoma and EGFR mutation even after repeated in vivo passages. Furthermore, the third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) osimertinib dramatically regressed tumors in these EGFR mutated PDX models. Osimertinib treatment is ongoing in these EGFR-mutated PDX models to obtain tumors that acquired resistance to osimertinib. Our PDX models of lung adenocarcinoma with different EGFR mutations may be useful for investigating the mechanisms of resistance to EGFR-TKIs, including third-generation inhibitor osimertinib. Citation Format: Kenji Kita, Koji Fukuda, Akihiro Nishiyama, Sachiko Arai, Shinji Takeuchi, Koushiro Ohtsubo, Kaname Yamashita, Masaya Tamura, Isao Matsumoto, Seiji Yano. Establishment of patient-derived xenograft models of lung adenocarcinoma with two different EGFR mutations, L858R and exon19 deletion [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A36.