title: The controversial role of ABC transporters in clinical oncology.
abstract: The phenomenon of multidrug resistance in cancer is often associated with the overexpression of the ABC (ATP-binding cassette) transporters Pgp (P-glycoprotein) (ABCB1), MRP1 (multidrug resistance-associated protein 1) (ABCC1) and ABCG2 [BCRP (breast cancer resistance protein)]. Since the discovery of Pgp over 35 years ago, studies have convincingly linked ABC transporter expression to poor outcome in several cancer types, leading to the development of transporter inhibitors. Three generations of inhibitors later, we are still no closer to validating the 'Pgp hypothesis', the idea that increased chemotherapy efficacy can be achieved by inhibition of transporter-mediated efflux. In this chapter, we highlight the difficulties and past failures encountered in the development of clinical inhibitors of ABC transporters. We discuss the challenges that remain in our effort to exploit decades of work on ABC transporters in oncology. In learning from past mistakes, it is hoped that ABC transporters can be developed as targets for clinical intervention.
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, Room 13N240, Bethesda, MD 20892, U.S.A.
authors.forename: Akina
authors.initials: A
authors.lastname: Tamaki
authors.forename: Caterina
authors.initials: C
authors.lastname: Ierano
authors.forename: Gergely
authors.initials: G
authors.lastname: Szakacs
authors.forename: Robert W
authors.initials: RW
authors.lastname: Robey
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bates
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006801:Humans; D008495:Medical Oncology; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents