Clinical management of recurrent breast cancer: development of multidrug resistance (MDR) and strategies to circumvent it.
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.
Hait
William N
WN
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
Yang
Jin-Ming
JM
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*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D051926:Basigin; D020782:Matrix Metalloproteinases