FBXW7 deletion contributes to lung tumor development and confers resistance to gefitinib therapy.

ABSTRACT: Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment for non-small-cell lung cancer (NSCLC) with EGFR activating mutations, but inevitably, the clinical efficacy is impeded by the emergence of acquired resistance. The tumor suppressor gene FBXW7 modulates chemosensitivity in various human cancers. However, its role in EGFR-TKI therapy in NSCLC has not been well studied. Here, we demonstrate that the mice with deficient Fbxw7 have greater susceptibility to urethane-induced lung tumor development. Through analysis of The Cancer Genome Atlas data, we show that deletion of FBXW7 occurs in 30.9% of lung adenocarcinomas and 63.5% of lung squamous cell carcinomas, which significantly leads to decrease in FBXW7 mRNA expression. The reductio

SUBMITTER: Xiao Y 

PROVIDER: S-EPMC5983212 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature