title: Clinical management of recurrent breast cancer: development of multidrug resistance (MDR) and strategies to circumvent it.
abstract: The multidrug resistance (MDR) phenotype is often associated with recurrent breast cancer. Many cytotoxic agents used to treat breast cancer, such as anthracyclines and taxanes, are susceptible to MDR-mediated loss of sensitivity to these agents. Overexpression of mdr-1/P-glycoprotein (P-gp) is one of the main mechanisms underlying the development of the MDR phenotype. Also involved in the development of the MDR phenotype are other proteins from the ATP-binding cassette family of transporters (eg, MRP, BCRP), as well as alterations of tumor targets and their downstream effector molecules. Additionally, P-gp expression in other anatomic locations (such as the brush border of the gastrointestinal epithelium and blood-brain barrier) may further compromise the success of treatment for patients with breast cancer. Several strategies have been developed to overcome or circumvent MDR, mostly through inhibition or modulation of P-gp. Despite successful proof of concept in the laboratory, to date none of these agents has had a major impact in the clinic.
authors.affiliation: University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, and The Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA. haitwn@umdnj.edu
authors.forename: William N
authors.initials: WN
authors.lastname: Hait
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000502:physiology*; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D051926:Basigin / Q000502:physiology; D001943:Breast Neoplasms / Q000628:therapy*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D051926:Basigin; D020782:Matrix Metalloproteinases