Erdafitinib Antagonizes ABCB1-Mediated Multidrug Resistance in Cancer Cells

Frontiers in Oncology
Weiguo FengDong-Hua Yang

Abstract

ABCB1 overexpression is known to contribute to multidrug resistance (MDR) in cancers. Therefore, it is critical to find effective drugs to target ABCB1 and overcome MDR. Erdafitinib is a tyrosine kinase inhibitor (TKI) of fibroblast growth factor receptor (FGFR) that is approved by the FDA to treat urothelial carcinoma. Previous studies have demonstrated that some TKIs exhibit MDR reversal effect. In this work, we examined whether erdafitinib could reverse MDR mediated by ABCB1. The results of reversal experiments showed that erdafitinib remarkably reversed ABCB1-mediated MDR without affecting ABCG2-mediated MDR. The results of immunofluorescence and Western blot analysis demonstrated that erdafitinib did not affect the expression of ABCB1 or its cellular localization. Further study revealed that erdafitinib inhibited ABCB1 efflux function leading to increasing intracellular drug accumulation, thereby reversing MDR. Furthermore, ATPase assay indicated that erdafitinib activated the ABCB1 ATPase activity. Docking study suggested that erdafitinib interacted with ABCB1 on the drug-binding sites. In summary, this study demonstrated that erdafitinib can reverse MDR mediated by ABCB1, suggesting that combination of erdafitinib and AB...Continue Reading

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Citations

Sep 29, 2020·Frontiers in Cell and Developmental Biology·Xing-Duo DongZhe-Sheng Chen
Feb 12, 2021·Journal of Hematology & Oncology·Sitong YueDaichao Wu
Jan 30, 2021·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Jing-Quan WangZhe-Sheng Chen
Jun 15, 2021·Biochemical Pharmacology·Jing-Quan WangZhe-Sheng Chen
Aug 14, 2021·Journal of Evidence-based Medicine·Jing-Quan WangZhe-Sheng Chen

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Methods Mentioned

BETA
Assay

Clinical Trials Mentioned

NCT02421185
NCT03238196
NCT02699606
NCT03999515

Software Mentioned

AutoDock Vina
GraphPad Prism

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