title: ABC transporters and neuroblastoma.
abstract: Neuroblastoma is the most common cancer of infancy and accounts for 15% of all pediatric oncology deaths. Survival rates of high-risk neuroblastoma remain less than 50%, with amplification of the MYCN oncogene the most important aberration associated with poor outcome. Direct transcriptional targets of MYCN include a number of ATP-binding cassette (ABC) transporters, of which ABCC1 (MRP1), ABCC3 (MRP3), and ABCC4 (MRP4) are the best characterized. These three transporter genes have been shown to be strongly prognostic of neuroblastoma outcome in primary untreated neuroblastoma. In addition to their ability to efflux a number of chemotherapeutic drugs, evidence suggests that these transporters also contribute to neuroblastoma outcome independent of any role in cytotoxic drug efflux. Endogenous substrates of ABCC1 and ABCC4 that may be potential candidates affecting neuroblastoma biology include molecules such as prostaglandins and leukotrienes. These bioactive lipid mediators have the ability to influence biological processes contributing to cancer initiation and progression, such as angiogenesis, cell signaling, inflammation, proliferation, and migration and invasion. ABCC1 and ABCC4 are thus potential targets for therapeutic suppression in high-risk neuroblastoma, and recently developed small-molecule inhibitors may be an effective strategy in treating aggressive forms of this cancer, as well as other cancers that express high levels of these transporters.
authors: Lowy Cancer Research Centre, Children's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
authors: Denise M T
authors: DM
authors: Yu
authors: Lowy Cancer Research Centre, Children's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
authors: Tony
authors: T
authors: Huynh
authors: Lowy Cancer Research Centre, Children's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
authors: Alan M
authors: AM
authors: Truong
authors: Lowy Cancer Research Centre, Children's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
authors: Michelle
authors: M
authors: Haber
authors: Lowy Cancer Research Centre, Children's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia. Electronic address: mnorris@ccia.unsw.edu.au.
authors: Murray D
authors: MD
authors: Norris
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001692:Biological Transport / Q000235:genetics; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007223:Infant; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009447:Neuroblastoma / Q000188:drug therapy; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D000242:Cyclic AMP; D006152:Cyclic GMP; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C513055:ABCB1 protein, human; C073492:ABCC4 protein, human; C116614:ABCG2 protein, human; C459801:MYCN protein, human; C114462:multidrug resistance-associated protein 3; C421109:multidrug resistance-associated protein 1
keywords: ABC transporter; Cancer; MYCN oncogene; Multidrug resistance; Neuroblastoma