ATP-binding cassette transporters, including ABCB1 (
P-glycoprotein) and ABCG2 (BCRP/MXR/ABCP), are pivotal in multidrug resistance (MDR) development in
cancer patients undergoing conventional
chemotherapy. The absence of approved therapeutic agents for multidrug-resistant
cancers presents a significant challenge in effectively treating
cancer. Researchers propose repurposing existing drugs to sensitize multidrug-resistant
cancer cells, which overexpress ABCB1 or ABCG2, to conventional anticancer drugs. The goal of this study is to assess whether
furmonertinib, a third-generation
epidermal growth factor receptor tyrosine kinase inhibitor overcomes drug resistance mediated by ABCB1 and ABCG2 transporters.
Furmonertinib stands out due to its ability to inhibit
drug transport without affecting
protein expression. The discovery of this characteristic was validated through
ATPase assays, which revealed interactions between
furmonertinib and ABCB1/ABCG2. Additionally, in silico docking of
furmonertinib offered insights into potential interaction sites within the
drug-binding pockets of ABCB1 and ABCG2, providing a better understanding of the underlying mechanisms responsible for the reversal of MDR by this repurposed
drug. Given the encouraging results, we propose that
furmonertinib should be explored as a potential candidate for combination
therapy in patients with
tumors that have high levels of ABCB1 and/or ABCG2. This combination
therapy holds the potential to enhance the effectiveness of conventional anticancer drugs and presents a promising strategy for overcoming MDR in
cancer treatment.