Analysis of Tumor Heterogeneity Through AXL Activation in Primary Resistance to EGFR Tyrosine Kinase Inhibitors

• DOI: 10.1016/j.jtocrr.2023.100525
• Publication Date: 2023-05-12T02:08:19Z
• Authors: Ryota Nakamura; Hiroyuki Fujii; Tadaaki Yamada; Yohei Matsui; Takeshi Yaoi; Mizuki Honda; Noriyuki Tanaka; Aya Miyagawa-Haya...; Akihiro Yoshimura; Kenji Morimoto; Masahiro Iwasaku; Shinsaku Tokuda; Young Hak Kim; Eiichi Konishi; Kyoko Itoh; Koichi Takayama
• Keywords: GAS6; Ramucirumab; T790M

EGFR tyrosine kinase inhibitors are standard therapeutic agents for patients with advanced NSCLC harboring mutations. Nevertheless, some exhibit primary resistance to in the first-line treatment setting. AXL, a member of TYRO3, and MERTK family receptor kinases, is involved EGFR-mutated NSCLC.We investigated spatial tumor heterogeneity using autopsy specimens patient-derived cell line from patient having erlotinib plus ramucirumab.Quantitative polymerase chain reaction analysis revealed that AXL mRNA expression differed at each metastatic site. In addition, levels were likely be negatively correlated effectiveness ramucirumab therapy. Analysis established left pleural effusion before initiation combination an inhibitor remarkably inhibited viability increased apoptosis comparison monotherapy or therapy these ramucirumab.Our observations suggest may play critical role progression NSCLC.