Targeting ADRB2 enhances sensitivity of non-small cell lung cancer to VEGFR2 tyrosine kinase inhibitors.

ABSTRACT: Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) tyrosine kinase inhibitors (TKIs) have achieved remarkable clinical progress in the treatment of non-small-cell lung cancer; however, resistance has limited their therapeutic efficacy. Therefore, understanding the mechanisms of VEGF-TKI and ICI resistance will help to develop effective treatment strategies for patients with advanced NSCLC. Our results suggested that treatment with VEGFR2-TKIs upregulated ADRB2 expression in NSCLC cells. Propranolol, a common ADRB2 antagonist, significantly enhanced the therapeutic effect of VEGFR2-TKIs by inhibiting the ADRB2 signaling pathway in NSCLC cells in vitro and in vivo. Mechanically, the treatment-induced ADRB2 upregulation and the enhancement of ADRB2/VEGFR2 interaction caused resistance to

SUBMITTER: Xu Y 

PROVIDER: S-EPMC8786837 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature