Malignant melanoma is among the most aggressive skin cancers and it has among the
highest metastatic potentials. Although surgery to remove the primary tumor is the
gold standard treatment, once melanoma progresses and metastasizes to the lymph nodes
and distal organs, i.e., metastatic melanoma (MM), the usual outcome is decreased
survival. To improve survival rates and life span, advanced treatments have focused
on the success of targeted therapies in the MAPK pathway that are based on BRAF (BRAF
V600E) and MEK. The majority of patients with tumors that have higher expression of
BRAF V600E show poorer prognosis than patients with a lower level of the mutated protein.
Based on the molecular basis of melanoma, these findings are supported by distinct
tumor phenotypes determined from differences in tumor heterogeneity and protein expression
profiles. With these aspects in mind, continued challenges are to: (1) deconvolute
the complexity and heterogeneity of MM; (2) identify the signaling pathways involved;
and (3) determine protein expression to develop targeted therapies. Here, we provide
an overview of the results from protein expression in MM and the link to disease presentation
in a variety of tumor phenotypes and how these will overcome the challenges of clinical
problems and suggest new promising approaches in metastatic melanoma and cancer therapy.
