Clinical management of recurrent breast cancer: Development of multidrug resistance (MDR) and strategies to circumvent it

William N. Hait, Jin-Ming Yang

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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.

Original languageEnglish (US)
JournalSeminars in oncology
Issue numberSUPPL. 7
StatePublished - Dec 1 2005


All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

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