Molecular mechanism and pharmacokinetics of flavonoids in the treatment of resistant EGF receptor‐mutated non‐small‐cell lung cancer: A narrative review
Xuewen Wang, Bing Chen, Dafen Xu, Zhijun Li, Hao Liu, Zhengjun Huang, Kangping Huang, Xinhua Lin, Hong Yao
Abstract
Here, we review the molecular mechanism and pharmacokinetics of flavonoids in the treatment of resistant EGF receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) and particularly the possible mechanism(s) of delicaflavone, a biflavonoid extracted from Selaginella doederleinii Hieron. EGFR TK inhibitors (EGFR-TKI) are ubiquitously used in the treatment of NSCLC bearing EGFR mutations. However, patients treated with EGFR-TKI inevitably and continuously develop resistance. In laboratory studies, flavonoids, as potential adjuvants for cancer chemotherapy, exhibited anti-cancer properties such as inhibition of chemoresistance by interference with ABC transporters-induced drug efflux, curbing of c-MET amplification, or reversal of T790M mutation-mediated resistance. The current review aims at summarizing the association between the anti-cancer potentials of flavonoids and their possible regulatory roles in certain types of mutation that could trigger EGFR-TKI resistance in NSCLC. Potential practical applications of these phytochemicals, as well as the relevant pharmacokinetics, are also discussed.