Cutaneous malignant melanoma (CMM) is an epidemic cancer in the United States. Survival rates for invasive CMM have not increased in past decades despite numerous clinical trials and the effective use of various combinations of chemotherapy agents to treat other cancers. Recent research has investigated the role of melanocortin 1 receptor (MC1R), a gene associated with red-hair phenotype in White individuals and with increased risk for developing CMM, in the mitogen-activated protein kinase (MAPK) pathway. This limited narrative review discusses the incidence, history, and risk factors for CMM. It explores familial CMM and provides a brief review of melanocyte development and melanogenesis. Histology of CMM and cytogenetic techniques used to identify CMM mutations is also discussed. The structure and function of MC1R is described, with particular attention to MC1R’s role in the MAPK pathway. Finally, the review touches on individualized therapy for CMM using genetic biomarkers and explores the promise of genomic research for finding effective treatments.
BandarchiB.MaL.NavabR.SethA.RastyG. (2010). From melanocyte to metastatic malignant melanoma. Dermatology Research and Practice, 2010, 583748. doi:10.1155/2010/583748
4.
BlokxW. A.Van DijkM. C.RuiterD. J. (2010). Molecular cytogenetics of cutaneous melanocytic lesions: Diagnostic, prognostic and therapeutic aspects. Histopathology, 56, 121–132.
5.
BoxN. F. (2001). MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations. American Journal of Human Genetics, 69, 765–773.
6.
BränströmR.KasparianN. A.AffleckP.TibbenA.ChangU.AzizE.…Newton-BishopJ. (2012). Perceptions of genetic research and testing among members of families with an increased risk of malignant melanoma. European Journal of Cancer, 48, 3052–3062.
7.
ChinL. (2003). The genetics of malignant melanoma: Lessons from mouse and man. Nature Reviews/Cancer, 3, 559–570.
8.
de SouzaC. F.MoraisA. S.JasiulionisM. G. (2012). Biomarkers as key contributors in treating malignant melanoma metastases. Dermatology Research and Practice, 2012, 156068.
9.
DessiniotiC.AntoniouC.KatsambasA.StratigosA. J. (2011). Melanocortin 1 receptor variants: Functional role and pigmentary associations. Photochemistry and Photobiology, 87, 978–987.
10.
FargnoliM. S.GandiniS.PerisK.MaisonneuveP.RaimondiS. (2010). MC1R variants increase in families with CDKN2A mutations: A meta-analysis. European Journal of Cancer, 46, 1413–1420.
11.
FecherL. A.AmaravadiR. K.FlahertyK. T. (2008). The MAPK pathway in melanoma. Current Opinions in Oncology, 20, 183–189.
12.
FlahertyK. T.HodiF. S.FisherD. E. (2012). From genes to drugs: Targeted strategies for melanoma. Nature Reviews Cancer, 12, 349–361.
GerstenblithM. R.GoldsteinA. M.TuckerM. A.FraserM. C. (2007). Genetic testing for melanoma predisposition: Current challenges. Cancer Nursing, 30, 452–459.
15.
HerraizC.Jimênez-CervantesC.ZannaP.García-BorrónJ. C. (2009). Melanocortin 1 receptor mutations impact differentially on signaling to the cAMP and the ERK mitogen-activated protein kinase pathways. Federation of European Biochemical Societies, 583, 3269–3274.
16.
HockerT. L.SinghM. K.TsaoH. (2008). Melanoma genetics and therapeutic approaches in the 21st century: Moving from the benchside to the bedside. Society for Investigative Dermatology, 128, 2575–2595.
17.
HoughtonA. N.PolskyD. (2002). Focus on melanoma. Cancer Cell, 2, 275–278.
18.
IbrahimN.HaluskaF. G. (2009). Molecular pathogenesis of cutaneous melanocytic neoplasms. Annual Review of Pathology: Mechanisms of Disease, 4, 551–579.
19.
ItoS.WakamatsuK. (2010). Human hair melanins: What we have learned and have not learned from mouse coat color pigmentation. Pigment Cell and Melanoma Research, 24, 63–74. doi:10.1111/j.1755-148X.2010.00755
20.
ItoS.WakamatsuK. (2011). Diversity of human hair pigmentation as studied by chemical analysis of eumelanin and pheomelanin. Journal of the European Academy of Dermatology and Venereology, 25, 1369–1380. doi:10.1111/j.1468-3083.2011.04278.x
PalmerJ. S.DuffyD. L.BoxN. F.AitkenJ. F.GormanL. E.GreenA. C.…SturmR. A. (2000). Melanocortin-1 receptor polymorphisms and risk of melanoma: Is the association explained solely by pigmentation phenotype?American Journal of Human Genetics, 66, 176–186.
27.
PankaD. J.AtkinsM. B.MierJ. W. (2006). Targeting the mitogen-activated protein kinase pathway in the treatment of malignant melanoma. Clinical Cancer Research, 12, 2371s–2375s.
28.
RhodesA. (2006). Cutaneous melanoma and intervention strategies to reduce tumor-related mortality: What we know, what we don’t know, and what we think we know that isn’t so. Dermatologic Therapy, 19, 50–69.
29.
ScheierB.AmariaR.LewisK.GonzalezR. (2011). Novel therapies in melanoma. Immunotherapy, 3, 1461–1469. doi:10.2217/imt.11.136
30.
SekulicA.HaluskaJr., P.MillerA. M.de LamoJ. G.EjadiS.PulidoJ. S.…MarkovicS. N. (2008). Malignant melanoma in the 21st century: The emerging molecular landscape. Mayo Clinic Proceedings, 83, 825–846.
31.
ShenenbergerD. W. (2012). Cutaneous malignant melanoma: A primary care perspective. American Family Physician, 85, 1661–1668.
SmalleyK. S. M. (2010). Understanding melanoma signaling networks as the basis for molecular targeted therapy. Journal of Investigative Dermatology, 130, 28–37.
van der VelenP. A. (2001). Melanocortin-1 receptor variant R151C modifies melanoma risk in Dutch families with melanoma. American Journal of Human Genetics, 69, 774–777.
