Nintedanib overcomes drug resistance from upregulation of FGFR signalling and imatinib-induced KIT mutations in gastrointestinal stromal tumours.

ABSTRACT: Drug resistance remains a major challenge in the clinical treatment of gastrointestinal stromal tumours (GISTs). While acquired on-target mutations of mast/stem cell growth factor receptor (KIT) kinase is the major resistance mechanism, activation of alternative signalling pathways may also play a role. Although several second- and third-generation KIT kinase inhibitors have been developed that could overcome some of the KIT mutations conferring resistance, the low clinical responses and narrow safety window have limited their broad application. The present study revealed that nintedanib not only overcame resistance induced by a panel of KIT primary and secondary mutations, but also overcame ERK-reactivation-mediated resistance caused by the upregulation of fibroblast growth factor (FGF) a

SUBMITTER: Liu J 

PROVIDER: S-EPMC9019892 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature