Involvement of ABC transporters in melanogenesis and the development of multidrug resistance of melanoma

Pigment Cell Melanoma Res. 2009 Dec;22(6):740-9. doi: 10.1111/j.1755-148X.2009.00630.x. Epub 2009 Aug 29.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Drug Resistance, Multiple / physiology*
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • Melanins / biosynthesis*
  • Melanocytes / cytology
  • Melanocytes / physiology
  • Melanoma / drug therapy
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Melanoma / physiopathology*
  • Melanosomes / metabolism
  • Models, Biological
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Melanins