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Molecules 2017, 22(4), 539; doi:10.3390/molecules22040539

Harnessing Solute Carrier Transporters for Precision Oncology

1
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
2
Department of Pharmaceutics, University of Washington, Seattle, WA 98195, USA
3
Division of Oncology, Department of Medicine, University of Washington, Seattle, WA 98195 USA
4
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Maria Emília de Sousa
Received: 27 February 2017 / Revised: 21 March 2017 / Accepted: 22 March 2017 / Published: 28 March 2017
(This article belongs to the Special Issue Can Membrane Transporters Contribute to Drug Discovery?)
View Full-Text   |   Download PDF [272 KB, uploaded 4 April 2017]

Abstract

Solute Carrier (SLC) transporters are a large superfamily of transmembrane carriers involved in the regulated transport of metabolites, nutrients, ions and drugs across cellular membranes. A subset of these solute carriers play a significant role in the cellular uptake of many cancer therapeutics, ranging from chemotherapeutics such as antimetabolites, topoisomerase inhibitors, platinum-based drugs and taxanes to targeted therapies such as tyrosine kinase inhibitors. SLC transporters are co-expressed in groups and patterns across normal tissues, suggesting they may comprise a coordinated regulatory circuit serving to mediate normal tissue functions. In cancer however, there are dramatic changes in expression patterns of SLC transporters. This frequently serves to feed the increased metabolic demands of the tumor cell for amino acids, nucleotides and other metabolites, but also presents a therapeutic opportunity, as increased transporter expression may serve to increase intracellular concentrations of substrate drugs. In this review, we examine the regulation of drug transporters in cancer and how this impacts therapy response, and discuss novel approaches to targeting therapies to specific cancers via tumor-specific aberrations in transporter expression. We propose that among the oncogenic changes in SLC transporter expression there exist emergent vulnerabilities that can be exploited therapeutically, extending the application of precision medicine from tumor-specific drug targets to tumor-specific determinants of drug uptake. View Full-Text
Keywords: solute carrier transporters; drug transport; chemotherapy; precision medicine; targeted therapy; SLC35F2; Survivin; YM155; precision oncology solute carrier transporters; drug transport; chemotherapy; precision medicine; targeted therapy; SLC35F2; Survivin; YM155; precision oncology
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Nyquist, M.D.; Prasad, B.; Mostaghel, E.A. Harnessing Solute Carrier Transporters for Precision Oncology. Molecules 2017, 22, 539.

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