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Review

The therapeutic potential of targeting ABC transporters to combat multi-drug resistance

, , , , , , & show all
Pages 511-530 | Received 18 Nov 2016, Accepted 21 Mar 2017, Published online: 03 Apr 2017
 

ABSTRACT

Introduction: Most disseminated cancers remain fatal despite the availability of a variety of conventional and novel treatments including surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy. A major factor responsible for the failure of chemotherapy in the treatment of cancer is the development of multidrug resistance (MDR). The overexpression of various ABC transporters in cancer cells can efficiently remove the anticancer drug from the cell, thus causing the drug to lose its effect.

Areas covered: In this review, we summarised the ongoing research related to the mechanism, function, and regulation of ABC transporters. We integrated our current knowledge at different levels from molecular biology to clinical trials. We also discussed potential therapeutic strategies of targeting ABC transporters to reverse MDR in cancer cells.

Expert opinion: Involvement of various ABC transporters to cancer MDR lays the foundation for developing tailored therapies that can overcome MDR. An ideal MDR reversal agent should have broad-spectrum ABC-transporter inhibitory activity, be potent, have good pharmacokinetics, have no trans-stimulation effects, and have low or no toxicity. Alternatively, nanotechnology-based drug delivery systems containing both the cytotoxic drug and reversing agent may represent a useful approach to reversing MDR with minimal off-target toxicity.

Article highlights

  • The overexpression of various ABC transporters in cancer cells can cause MDR.

  • Inhibitors of ABC transporters to reverse MDR have yielded few clinical successes.

  • Better understanding of ABC transporters and pharmacokinetics is necessary for developing an ideal ABC transporter inhibitor.

  • Nanotechnology-based drug delivery systems containing both the cytotoxic drug and reversing agent may represent a novel approach to reverse MDR.

  • This box summarizes key points contained in the article.

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.

Additional information

Funding

This paper was not funded.

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