Melanoma is a form of skin cancer that originates from specialized cells in the skin called melanocytes. Environmental, biochemical, molecular and genetic factors are all involved in the genesis of melanoma. Although the incidence of melanoma continues to rise worldwide, no current effective treatment is available for metastatic disease. Thus, development of new and efficacious strategies to treat this aggressive disease is urgently needed. Understanding the molecular and cellular basis of melanoma initiation, progression and metastasis is critical to identify new targets for novel therapeutic approaches that would improve survival and offer hope to patients coping with this aggressive neoplasm.

Key Concepts:

  • Melanoma is a serious form of skin cancer that originates from pigment‐producing cells called melanocytes.

  • The incidence of melanoma continues to rise worldwide, constituting a serious public health problem.

  • Major risk factors for melanoma include exposure to UV radiation, fair skin, large number of dysplastic nevi and a family history of melanoma.

  • Multiple factors, including genetic, molecular and environmental contribute to the development of melanoma.

  • Mutations in genes critical for proliferation (e.g. BRAF) and survival (e.g. AKT) contribute to melanomagenesis.

  • Metastatic melanoma is highly resistant to current therapies.

  • Targeting signalling pathways that are essential for tumour progression and maintenance, such as BRAF/MAPK and PI3K/AKT, offer a rational approach for the development of effective antimelanoma therapies

Keywords: melanoma; skin cancer; signal transduction; progression; targeted therapy

Figure 1.

Melanoma development and progression. Melanoma progression is usually regarded as a stepwise process in which normal mature melanocytes become transformed and progress into malignancy. Transformation of melanocytes into melanoma is dependent on genetic and environmental factors, in particular UV radiation. Acquisition of malignancy and metastatic potential can be influenced by the tumour microenvironment, composed of nontransformed cells including fibroblasts, endothelial cells and immune cells. Growth factors and ECM‐dependent signalling mediates crosstalk between the tumour cells and the cells in the microenvironment. In some instances advanced melanomas can develop directly from normal melanocytes without going through each of the stages depicted in the model.

Figure 2.

Dysregulated signalling in melanoma. Multiple signalling pathways mediating important cellular process are activated in melanoma. Activation of these pathways, including MAPK and PI3K are important for melanoma initiation, progression and maintenance. Activating mutations, gene amplification or overexpression as well as inactivating mutations or deletions can lead to dysregulated activity of these pathways. Receptor tyrosine kinases, integrins and G‐coupled receptors can activate the RAS/RAF/MAPK as well as the PI3K pathway. Signalling through these pathways ultimate regulate proliferation, survival, migration and invasion.



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Villanueva, Jessie, and Herlyn, Meenhard(Mar 2009) Melanoma. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001894.pub2]