The role of membrane transporters in ovarian cancer chemoresistance and prognosis

ABSTRACT

Introduction: Ovarian cancer has the highest mortality rate of all cancers in women. There is currently no effective method for early diagnosis, limiting the precision of clinical expectations. Predictions of therapeutic efficacy are currently not available either. Specifically, the development of chemoresistance against conventional chemotherapy poses a fundamental complication. Some membrane transporters have been reported to influence chemoresistance, which is often associated with a poor prognosis.

Areas covered: The aim of this article is to review the existing information about membrane transporters and their role in both ovarian cancer chemoresistance and its outcomes. We then highlight limitations of current methodologies and suggest alternatives providing avenues for future research.

Expert opinion: Membrane transporters play an important role in development of chemoresistance and affect prognosis of ovarian cancer patients; however, due to variations in methodology and in patient populations, their specific roles have yet to be clarified. For further evaluation of the clinical utility of membrane transporters, it is essential to validate results and improve methods for marker assessment across laboratories. A promising area for future research is to identify the genetic variability in potential markers in peripheral blood. These markers would then stratify patients into defined groups for optimal intervention.

KEYWORDS:

• Ovarian cancer
• chemoresistance
• membrane transporters
• expression
• prognosis

Article highlights

• Ovarian cancer has the highest mortality rate of all cancers in women

• Membrane transporters play an important role in chemoresistance

• ABC transporters affect ovarian cancer through drug efflux and dysregulation of sterol homeostasis

• SLC transporters import and export of drugs, and ATPase-mediated dysregulation of copper homeostasis, can each affect resistance indirectly

• Expression or genetic variability of certain transporters correlates with patients´ prognosis in vivo and resistance to therapy in vitro

• When validated, these markers could help to stratify patients into prognostic groups and facilitate the use of personalized medicine

This box summarizes key points contained in the article.

Acknowledgments

Authors would like to express their sincere thanks to Prof. Sarah Leupen, Ph.D., (Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD and U.S. Fulbright Scholar at Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic) for reading and critical comments on the manuscript.

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 work was supported by the Czech Science Foundation (project no. P303/12/G163) and by the National Sustainability Program I (NPU I) (project no. LO1503), provided by the Ministry of Education Youth and Sports of the Czech Republic.