Oncogenic activation of the fibroblast growth factor receptor(FGFR)through mutations and fusions of the FGFR gene occur in a variety of different malignancies such as urothelial carcinoma and cholangiocarcinoma.Inhibi...Oncogenic activation of the fibroblast growth factor receptor(FGFR)through mutations and fusions of the FGFR gene occur in a variety of different malignancies such as urothelial carcinoma and cholangiocarcinoma.Inhibition of the kinase domain of the FGFR with targeted oral FGFR inhibitors has been shown in both preclinical and early phase clinical trials to lead to meaningful reductions in tumour size and larger confirmatory randomized trials are underway.Acquired resistance to FGFR inhibition using a variety of mechanisms that includes,activation of alternate signaling pathways and expansion of tumour clones with gatekeeper mutations in the FGFR gene.This review summarizes the acquired resistance mechanisms to FGFR therapy and therapeutic approaches to circumventing resistance.展开更多
基金Lau DK received financial support from La Trobe University(Australian Postgraduate Award),Pancare/RMA NetworkJenkins L received financial support from La Trobe University(Australian Postgraduate Award)Weickhardt A has received consulting fees from Merck,Novartis,Pfizer and Ipsen.
文摘Oncogenic activation of the fibroblast growth factor receptor(FGFR)through mutations and fusions of the FGFR gene occur in a variety of different malignancies such as urothelial carcinoma and cholangiocarcinoma.Inhibition of the kinase domain of the FGFR with targeted oral FGFR inhibitors has been shown in both preclinical and early phase clinical trials to lead to meaningful reductions in tumour size and larger confirmatory randomized trials are underway.Acquired resistance to FGFR inhibition using a variety of mechanisms that includes,activation of alternate signaling pathways and expansion of tumour clones with gatekeeper mutations in the FGFR gene.This review summarizes the acquired resistance mechanisms to FGFR therapy and therapeutic approaches to circumventing resistance.
