Melanocyte receptors: clinical implications and therapeutic relevance.
The activation or the inhibition of melanocyte-specific receptors offers novel means of augmenting normal melanocyte function, skin color, and photoprotection, or treating melanocytic disorders, namely at this time, metastatic melanoma. Melanocyte-specific receptors include melanocortin-1 (MCR1) and melatonin receptors. Other receptors that play an important role in melanoma progression are G-protein couple receptors such as Frizzled 5 and receptor tyrosine kinases such as c-Kit and hepatocyte growth factor (HGF) receptor. These receptors activate two crucial cell-signaling pathways, RAS/RAF/MEK/ERK and PI3K/AKT, integral to melanoma cell survival, and can serve as targets for therapy of disseminated melanoma. Activation of death receptors is another pathway that can be exploited with targeted therapeutics to control advanced melanoma. This article reviews the current understanding of melanocyte receptors, their agonists and inhibitors, and their potential to treat the melanocytic pathology.
Carlson
J Andrew
JA
Division of Dermatopathology and Dermatology, Department of Pathology and Laboratory Medicine, Albany Medical College MC-81, 47 New Scotland Avenue, Albany, NY 12208, USA. carlsoa@mail.amc.edu
Linette
Gerald P
GP
Aplin
Andrew
A
Ng
Bernard
B
Slominski
Andrzej
A
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008544:Melanocytes / Q000502:physiology*; D008545:Melanoma / Q000188:drug therapy / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000188:drug therapy; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000503:physiopathology*
D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear