Involvement of ABC transporters in melanogenesis and the development of multidrug resistance of melanoma.
Because melanomas are intrinsically resistant to conventional radiotherapy and chemotherapy, many alternative treatment approaches have been developed such as biochemotherapy and immunotherapy. The most common cause of multidrug resistance (MDR) in human cancers is the expression and function of one or more ATP-binding cassette (ABC) transporters that efflux anticancer drugs from cells. Melanoma cells express a group of ABC transporters (such as ABCA9, ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, and ABCD1) that may be associated with the resistance of melanoma cells to a broad range of anticancer drugs and/or of melanocytes to toxic melanin intermediates and metabolites. In this review, we propose a model (termed the ABC-M model) in which the intrinsic MDR of melanoma cells is at least in part because of the transporter systems that may also play a critical role in reducing the cytotoxicity of the melanogenic pathway in melanocytes. The ABC-M model suggests molecular strategies to reverse MDR function in the context of the melanogenic pathway, which could open therapeutic avenues towards the ultimate goal of circumventing clinical MDR in patients with melanoma.
Chen
Kevin G
KG
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Valencia
Julio C
JC
Gillet
Jean-Pierre
JP
Hearing
Vincent J
VJ
Gottesman
Michael M
MM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000502:physiology; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D020460:Melanosomes / Q000378:metabolism; D008954:Models, Biological; D000089762:Multidrug Resistance-Associated Protein 2; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism
C000715087:ABCC2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D008543:Melanins; D000089762:Multidrug Resistance-Associated Protein 2