title: The interactions of anti-cancer drugs approved in the last decade in the United States with membrane transporters.
abstract: Membrane transporters play a role in determining the absorption, distribution, metabolism and excretion of small molecule anticancer drugs and mediating chemosensitivity and resistance of tumor cells to these drugs. Our understanding of the influence of these transporters on the pharmacokinetics, clinical effectiveness and tolerability has considerably increased in the last decade. Therefore, determining the interaction of membrane transporters with small molecule anticancer drugs can facilitate the development of effective and safe treatments. We reviewed the interaction of the small molecule anticancer drugs approved in the last decade with the more common membranes transporters, such as ABCB1, ABCG2, and OATP. The drugs were divided into three categories: targeted therapies, cytotoxic agents and hormonal therapies. The literature appears to focus on the interaction of the targeted therapies compared to the remaining two categories. Furthermore, most data stemmed from nonclinical studies with only a few clinical examples where transporters corresponded with systemic exposure or clinical effectiveness or tolerability. More nonclinical and clinical studies are needed to improve the ability to use the findings from these nonclinical studies to predict clinical outcomes, but the literature appears to be rapidly expanding as our understanding of these transporters groups. Therefore, determining the interaction of membrane transporters with small molecule anticancer drugs can be facilitate the development of effective and safe treatment.
authors.affiliation: Division of Clinical Pharmacology 2, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U. S. Food and Drug Administration, Silver Spring , MD 20993, USA. Lokesh.Jain@fda.hhs.gov
authors.forename: Lokesh
authors.initials: L
authors.lastname: Jain
authors.forename: Sophia
authors.initials: S
authors.lastname: Abraham
authors.forename: Stacy S
authors.initials: SS
authors.lastname: Shord
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001692:Biological Transport; D002986:Clinical Trials as Topic; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy; D014481:United States
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D026901:Membrane Transport Proteins