Melanoma: A Therapeutic Revolution Happening Before Our Eyes
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Abstract
Malignant melanoma (MM) is among the most common cancers in the world. Although incidence has been increasing worldwide, most of the cases have been reported to occur in the European continent. Risk factors for the development of MM have been clearly recognized; yet, the accepted theory is that the risk of melanoma is highly determined by the interplay between genetic factors and exposure to sunlight. Morphological characteristics classify melanoma into four subtypes: Superficial spreading melanoma (SSM); nodular melanoma (NM), Lentigo maligna (LM) and Acral lentiginous melanoma (ALM). SSM represents approximately 70% of the cases. Mitogen-activated protein kinase (MAPK) has been identified as a key regulatory element in most melanomas. MAPK is the most relevant signal pathway in the development of melanoma; while the microphthalmia-associated transcription factor (MITF) is a target of extracellular signal-related kinase (ERK) and controls the production of the pigment melanin, cell cycling and survival. Surgical resection is still considered the cornerstone of the treatment in the vast majority of patients with early-stage melanoma. However, treatment of metastatic or recurrent melanoma has significantly been improved with the advent of targeted immunotherapies. The greatest advantage has been observed with the use of checkpoint-inhibitor immunotherapy. But, Adoptive cell therapy (ACT) for the treatment of metastatic melanoma, in patients who have progressed to immunotherapy and/or targeted therapies without success, is currently under investigation with promising results.
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