title: Loss of OATP1B3 function causes Rotor syndrome: implications for potential use of inhibitors in cancer.
abstract: There has been increasing recognition that organic anion transporter proteins (OATPs) play an important role in the biology of various cancers. De novo expression of OATPs has been identified in breast, colon, pancreatic, gastric and prostate cancer cells, among others. In patients with prostate cancer, polymorphisms encoding decreased functioning OATP1B3 were associated with a longer time to progression on androgen deprivation therapy and a longer overall survival which is likely caused by reduced tumoral testosterone uptake. Because of these findings, therapeutic inhibition targeting OATP1B3 has been proposed. However, any enthusiasm for inhibiting OATP1Bs therapeutically has been tempered by reservations about potential consequences. For instance, inhibitors could interfere with several normal physiological processes mediated by OATP1B3 (i.e., bile acid reuptake, bilirubin uptake, etc) or cause potential, as-yet unknown, drug interactions by barring hepatic uptake, subsequent metabolism and elimination.
authors.affiliation: Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute; Bethesda, MD 20892, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Pratt
authors.forename: Tristan M
authors.initials: TM
authors.lastname: Sissung
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
mesh_terms: D000818:Animals; D001692:Biological Transport; D006801:Humans; D006933:Hyperbilirubinemia, Hereditary / Q000235:genetics / Q000378:metabolism*; D027381:Liver-Specific Organic Anion Transporter 1; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
chemical_list: D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3