Overcoming multidrug resistance through targeting ABC transporters: lessons for drug discovery

ABSTRACT

Introduction

The argument around cancer therapy is an old one. Using chemotherapeutic drugs, as one of the most effective strategies in treatment of malignancies, is restricted by various issues that progress during therapy and avoid achieving clinical endpoints. Multidrug resistance (MDR), frequently mediated by ATP-binding cassette (ABC) transporters, is one of the most recognized obstacles in the success of pharmacological anticancer approaches. These transporters efflux diverse drugs to extracellular environment, causing MDR and responsiveness of tumor cells to chemotherapy diminishes.

Areas covered

Several strategies have been used to overcome MDR phenomenon. Succession in this field requires complete knowledge about features and mechanism of ABC transporters. In this review, conventional synthetic and natural inhibitors are discussed first and then novel approaches including RNA, monoclonal antibodies, nanobiotechnology, and structural modification techniques are represented.

Expert opinion

With increasing frequency of MDR in cancer cells, it is essential to develop new drugs to inhibit MDR. Using knowledge acquired about ABC transporter’s structure, rational design of inhibitors is possible. Also, some herbal products have shown to be potential lead compounds in drug discovery for reversal of MDR.

KEYWORDS:

• ABC transporter
• ATP-binding cassette
• cancer
• chemotherapy
• multidrug resistance

Article highlights

• One of the major obstacles in successful chemotherapy of cancer is multidrug resistance.

• Efflux of drugs via ABC transporters is a noticeable mechanism in developing resistance in cancer cells.

• Characterization of structure and mechanism of different ABC transporters is essential in new inhibitor drugs discovery.

• Derivatives of common anticancer drugs and herbal products could serve as lead compounds in drug development.

• Combination of different strategies in overcoming MDR can increase the efficiency of either method alone.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by Tabriz University of Medical Sciences, Tabriz-Iran (Grant number: 68360).