Human multidrug transporter ABCG2, a target for sensitizing drug resistance in cancer chemotherapy.
Human ABCG2, a member of the ATP-binding cassette transporter superfamily which transports a wide variety of substrates, is highly expressed in placental syncytiotrophoblasts, in the canalicular membranes of liver, in the apical membrane of the small intestine epithelium, and at the luminal surface of the endothelial cells of human brain micro vessels. This strategic tissue localization indicates that ABCG2 plays an important role in absorption, distribution, and elimination of xenobiotics and drugs. High ABCG2 expression has also been detected in many hematological malignancies and solid tumors, indicating that ABCG2 is likely responsible also for the multidrug resistance in cancer chemotherapy. Indeed, ABCG2 can actively transport structurally diverse conjugated- or unconjugated-organic molecules and various anticancer drugs. Many chemo-sensitizing agents have been discovered, which can be developed for increasing drug adsorption and reversing drug resistance in cancer chemotherapy by inhibiting ABCG2 function or expression. This review summarizes current knowledge on ABCG2, its relevance to multidrug resistance and drug disposition, and its ever-growing numbers of substrates and inhibitors.
Xu
Junkang
J
Department of Pharmacology and Toxicology, Indiana University Cancer Center, Walther Oncology Center/Walther Cancer Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Peng
Hui
H
Zhang
Jian-Ting
JT
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins