Perspectives on drug repurposing to overcome cancer multidrug resistance mediated by ABCB1 and ABCG2

Area of Science:

• Biochemistry
• Pharmacology
• Oncology

Background:

• Overexpression of ATP-binding cassette (ABC) transporters in cancer cells drives multidrug resistance (MDR).
• Multidrug resistance (MDR) poses a significant challenge to effective chemotherapy, with no specific treatments currently approved.
• Developing novel transporter-specific inhibitors has faced considerable difficulties over two decades of research.

Purpose of the Study:

• To review the mechanisms of ABCB1 and ABCG2 transporters and their role in cancer MDR.
• To evaluate existing and repurposed drugs as inhibitors of ABCB1 and ABCG2 to reverse MDR.
• To explore the challenges and future prospects of using repurposed drugs to combat chemoresistance.

Main Methods:

• Literature review focusing on ABCB1 and ABCG2 mechanisms in MDR.
• Analysis of studies evaluating drug repurposing for MDR reversal.
• Assessment of approved drugs tested for inhibitory activity against ABC drug efflux pumps.

Main Results:

• Discussion of ABCB1 and ABCG2 roles in mediating cancer multidrug resistance.
• Overview of various inhibitors evaluated for their potential to overcome MDR.
• Identification of approved drugs with demonstrated inhibitory effects on these transporters.

Conclusions:

• Drug repurposing presents a viable and practical approach to developing new therapies for multidrug-resistant cancers.
• Approved medications can be repurposed to inhibit ABCB1 and ABCG2, offering a faster route to clinical application.
• Further research into drug repurposing holds promise for overcoming chemoresistance in patients with high ABC transporter expression.