Drug transporters in breast cancer: response to anthracyclines and taxanes

Abstract

Despite the advances that have taken place in the past decade, including the development of novel molecular targeted agents, cytotoxic chemotherapy remains the mainstay of cancer treatment. In breast cancer, anthracyclines and taxanes are the two main chemotherapeutic options used on a routine basis. Although effective, their usefulness is limited by the inevitable development of resistance, a lack of response to drug-induced cancer cell death. A large body of research has resulted in the characterization of a plethora of mechanisms involved in resistance; ATP-binding cassette transporter proteins, through their function in xenobiotic clearance, play an important role in resistance. We review here the current evidence for drug transporters as biomarkers and the benefit of adding drug transporter modulators to conventional chemotherapy.

Keywords:

• anthracyclines
• breast cancer
• drug transporters
• multidrug resistance
• taxanes

Financial & competing interests disclosure

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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• ABC cassette efflux pumps are critically involved in resistance to chemotherapy.

• Research on these pumps has, for some reason, declined during the past decade.

• New studies on the value of measurements of the pumps in cancer tissue as predictive biomarkers are needed.

• Research should focus on novel strategies to inhibit the function of the pumps.

• Clinical studies performed according to current guidelines should be undertaken to prove or disapprove the value of adding pump inhibitors to current chemotherapy in preselected patients, that is, in patients with tumors expressing the pumps.