Molecular mechanism and pharmacokinetics of flavonoids in the treatment of resistant EGF receptor-mutated non-small-cell lung cancer: A narrative review

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.