Organic Anion Transporting Polypeptides: Emerging Roles in Cancer Pharmacology

Abstract

The organic anion transporting polypeptides (OATPs) are a superfamily of drug transporters involved in the uptake and disposition of a wide array of structurally divergent endogenous and exogenous substrates, including steroid hormones, bile acids, and commonly used drugs, such as anti-infectives, antihypertensives, and cholesterol lowering agents. In the past decade, OATPs, primarily OATP1A2, OATP1B1, and OATP1B3, have emerged as potential mediators of chemotherapy disposition, including drugs such as methotrexate, doxorubicin, paclitaxel, docetaxel, irinotecan and its important metabolite 7-ethyl-10-hydroxycamptothecin, and certain tyrosine kinase inhibitors. Furthermore, OATP family members are polymorphic and numerous studies have shown OATP variants to have differential uptake, disposition, and/or pharmacokinetics of numerous drug substrates with important implications for interindividual differences in efficacy and toxicity. Additionally, certain OATPs have been found to be overexpressed in a variety of human solid tumors, including breast, liver, colon, pancreatic, and ovarian cancers, suggesting potential roles for OATPs in tumor development and progression and as novel targets for cancer therapy. This review focuses on the emerging roles for selected OATPs in cancer pharmacology, including preclinical and clinical studies suggesting roles in chemotherapy disposition, the pharmacogenetics of OATPs in cancer therapy, and OATP overexpression in various tumor tissues with implications for OATPs as therapeutic targets.

A guide to plasma membrane solute carrier proteins

“…The SLCO family of transporters has been increasingly investigated in the past years for their potential role in the transport of chemotherapeutics and their potential impact on efficacy of therapies [543]. This interest has particularly focused on SLCO1A2, SLCO1B1, SLCO1B3, and SLCO2B1 [525,526,544].…”

Slow-, Tight-Binding Inhibition of CYP17A1 by Abiraterone Redefines Its Kinetic Selectivity and Dosing Regimen

“…intratumoural levels of abiraterone could be reasonably higher than that predicted by Kp,uu (Schulte and Ho, 2019). Additionally, another key assumption underpinning the free drug hypothesis is that This article has not been copyedited and formatted.…”

Role of OATP1B1 and OATP1B3 in Drug-Drug Interactions Mediated by Tyrosine Kinase Inhibitors

“…In another study, 44.7% of the potential DDIs identified involving TKIs were considered severe [ 29 ]. Interestingly, most available data in this field have investigated TKIs as victims in DDIs [ 30 , 31 , 32 , 33 ], and conclusive information on their role as perpetrators in DDIs is generally lacking.…”