Abstract 4161: Increased expression of ABCB1 could be associated with osimertinib resistance in non-small cell lung cancer cell line PC9 cell

Osimertinib, a third-generation EGFR Tyrosine kinase inhibitor, has shown promising activity in EGFR mutation positive non-small cell lung cancer (NSCLC) which harboring T790M mutation. The mechanisms of resistance to osimertinib have been still unclear. To investigate the mechanisms of acquired resistance to osimertinib, we established the osimertinib-resistant cell line (PC9/osimertinib) from the NSCLC cell lines PC9, and measured the expression levels of ATP-binding cassette (ABC) transporters using quantitative real-time polymerase chain reaction. Expression profiling of ABC transporters revealed that the levels of ABCB1 gene expression were significantly increased in the PC9/osimertinib cells compared with the parental cells, but not other ABC transporters. Knockdown of ABCB1 expression using short hairpin RNA enhanced osimertinib cytotoxicity in PC9/osimertinib cells. These data suggest that increased expression of ABCB1 may have an important role in the acquired resistance to osimertinib. Citation Format: Takashi Nomizo, Hiroaki Ozasa, Takahiro Tsuji, Yuto Yasuda, Tomoko Funazo, Hironori Yoshida, Yuichi Sakamori, Hiroki Nagai, Young Hak Kim. Increased expression of ABCB1 could be associated with osimertinib resistance in non-small cell lung cancer cell line PC9 cell [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4161. doi:10.1158/1538-7445.AM2017-4161