The Role of Melanocortin 1 Receptor in Cutaneous Malignant Melanoma

Abstract

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.

Why target the tumor stroma in melanoma?

“…It has been theorized that this newfound ability to communicate and attach to fibroblasts might be instrumental in facilitating the transition from the radial growth phase to the vertical growth phase (Haass and Herlyn 2005). At this point the tumor is fully competent to invade and metastasize to distant organs, though continuing accumulation of mutations may speed this process (Steck 2014). Once metastasis to distant organs has occurred, the tumor has entered its final stage is now termed metastatic melanoma.…”

“…The third stage, known as the radial growth phase is characterized by a cancerous histological phenotype, rapid growth across the epidermis with only minor incursions across the basement membrane, and constitutive activation of ERK signaling to drive rapid clonal cell proliferation (Haass and Herlyn 2005; Miller and Mihm 2006; Shain and Bastian 2016). Explanted cells from lesions in the radial growth phase, or any earlier phase, are typically unable to produce colonies in soft agar, as they are typically reliant on exogenous growth factors (Miller and Mihm 2006; Steck 2014). Since the cells are largely unable to penetrate deeper than the basement membrane, surgical excision up to this stage remains highly effective (Steck 2014).…”

“…Explanted cells from lesions in the radial growth phase, or any earlier phase, are typically unable to produce colonies in soft agar, as they are typically reliant on exogenous growth factors (Miller and Mihm 2006; Steck 2014). Since the cells are largely unable to penetrate deeper than the basement membrane, surgical excision up to this stage remains highly effective (Steck 2014).…”