title: ATP-binding cassette transporters in tumor endothelial cells and resistance to metronomic chemotherapy.
abstract: Drug resistance is a major problem in anticancer therapy. ATP-binding cassette (ABC) transporters have a role in the multidrug resistance. A new regimen of chemotherapy has been proposed, called "metronomic chemotherapy". Metronomic chemotherapy is the frequent, regular administration of drug doses designed to maintain low, but active, concentrations of chemotherapeutic drugs over prolonged periods of time, without causing serious toxicities. Metronomic chemotherapy regimens were developed to optimize the antitumor efficacy of agents that target the tumor vasculature instead of tumor cells, and to reduce toxicity of antineoplastic drugs [1]. Nevertheless, recent studies revealed that ABC transporters are expressed at a higher level in the endothelium in the tumor. To avoid resistance to metronomic anti-angiogenic chemotherapy, ABC transporter inhibition of tumor endothelial cells may be a promising strategy. In this mini-review, we discuss the possible mechanism of resistance to metronomic chemotherapy from the viewpoint of tumor endothelial cell biology, focusing on ABC transporters.
authors.affiliation: Vascular Biology, Frontier Research Unit, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan. Electronic address: khida@igm.hokudai.ac.jp.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hida
authors.affiliation: Vascular Biology, Frontier Research Unit, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan; Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kikuchi
authors.affiliation: Vascular Biology, Frontier Research Unit, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Nako
authors.initials: N
authors.lastname: Maishi
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hida
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D059250:Administration, Metronomic; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D018528:ATP-Binding Cassette Transporters; D020533:Angiogenesis Inhibitors
keywords: ABC transporters; Anti-angiogenic therapy; Drug resistance; Metronomic chemotherapy; Tumors endothelial cells