Multidrug resistance/P-glycoprotein and breast cancer: review and meta-analysis.
Previously untreated breast cancer is relatively sensitive to a range of anticancer drugs. However, exposure to these drugs is often followed by acquisition of multidrug resistance, which is associated with a significantly worse outcome. One of the more widely studied mechanisms of drug resistance is the function of P-glycoprotein (P-gp), a membrane transporter with a wide range of substrates, including several anticancer agents, and a member of the ATP-binding cassette superfamily of proteins. A review of the published literature indicates that P-gp expression is detected in a significant percentage of breast cancers. Moreover, P-gp expression is increased after exposure to chemotherapeutic drugs (particularly those known to be P-gp substrates), and correlates with a worse response to treatment, especially when detected following treatment, in both the adjuvant and neoadjuvant settings. Consequently, P-gp represents a potential biomarker of drug resistance. However, a direct role of P-gp as a cause of clinical drug resistance has not been adequately tested in breast cancer. Future studies aimed at validating the mechanistic role of P-gp should include trials of multidrug resistance reversal using P-gp-specific inhibitors and relating results to the levels of P-gp expression. Future studies should also take into account the potentially multifactorial nature of multidrug resistance.
Clarke
Robert
R
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA. clarker@georgetown.edu
Leonessa
Fabio
F
Trock
Bruce
B
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000502:physiology*; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents