Biomarkers as Key Contributors in Treating Malignant Melanoma Metastases

Abstract

Melanoma is a human neurocristopathy associated with developmental defects in the neural crest-derived epidermal melanocytes. At the present time, at least three hypotheses were identified that may explain melanoma aetiology, as follows: (1) a model of linear progression from differentiated melanocytes to metastatic cancer cells (2) a model involving the appearance of melanoma stem-like cells, and (3) an epigenetic progenitor model of cancer. Treating metastatic melanoma is one of the most serious challenges in the 21st century. This is justified because of a subpopulation of cells presenting a remarkable molecular heterogeneity, which is able to explain the drug resistance and the growing mortality rates worldwide. Fortunately, there are now evidences sustaining the importance of genetic, epigenetic, and metabolomic alterations as biomarkers for classification, staging, and better management of melanoma patients. To illustrate some fascinating insights in this field, the genes BRAF V600E and CTLA4 have been recognized as bona fide targets to benefit melanoma patients. Our research attempts to carefully evaluate data from the literature in order to highlight the link between a molecular disease model and the key contribution of biomarkers in treating malignant melanoma metastases.

The Role of Tumor Microenvironment in Melanoma Therapy Resistance

“…Advances in molecular medicine have reclassified melanoma as a highly complex heterogeneous disease comprising of several subpopulations of tumor cells [4,5]. These tumor cells harbor a number of distinct gene mutations and aberrant cell-signaling pathways [2,4,5,15].…”

“…These tumor cells harbor a number of distinct gene mutations and aberrant cell-signaling pathways [2,4,5,15]. Discovery of new generation of targeted-therapy drugs such as vemurafenib and dabrafenib targeting BRAFV600E mutation of the MAPK pathway or MEK inhibitors such as cobimetinib or trametinib targeting MEK have led to a substantial increase in overall response rate and has extended the survival of melanoma patients [6,[15][16][17].…”

“…Although patients with early stage of melanoma can be cured with surgical excision of the primary tumor, treatment of advanced metastatic melanoma patients continues to be a major challenge [2]. This is due to the rapid development of resistance to most available therapies including chemotherapy and targeted-therapy drugs [2][3][4][5][6]. Until very recently, melanoma was considered as a single disease entity and was treated with dacarbazine, an alkylating agent, or temozolomide, a second-generation drug derivative of dacarbazine.…”

“…Until very recently, melanoma was considered as a single disease entity and was treated with dacarbazine, an alkylating agent, or temozolomide, a second-generation drug derivative of dacarbazine. The objective response rate with these drugs was low (<15%) and it had limited overall survival benefits [5].…”

Nivolumab in combination with ipilimumab for the treatment of melanoma

“…Despite major strides in molecular medicine, the treatment of metastatic melanoma continues to be a challenge. This is due to the rapid development of resistance to most available chemo-and targeted therapy drugs [4,6,7]. Until very recently, melanomas were considered as a single disease entity and most patients were treated with dacarbazine (DTIC), an alkylating agent, or temozolomide, a second-generation drug derivative of DTIC.…”