title: Harnessing Solute Carrier Transporters for Precision Oncology.
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.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. mnyquist@fredhutch.org.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Nyquist
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, WA 98195, USA. bhagwat@uw.edu.
authors.forename: Bhagwat
authors.initials: B
authors.lastname: Prasad
authors.affiliation: Division of Oncology, Department of Medicine, University of Washington, Seattle, WA 98195 USA. emostagh@fredhutch.org.|Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. emostagh@fredhutch.org.
authors.forename: Elahe A
authors.initials: EA
authors.lastname: Mostaghel
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001692:Biological Transport; D002986:Clinical Trials as Topic; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D057285:Precision Medicine; D000070590:Solute Carrier Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D000070590:Solute Carrier Proteins
keywords: SLC35F2; Survivin; YM155; chemotherapy; drug transport; precision medicine; precision oncology; solute carrier transporters; targeted therapy