Overview of genetic signaling pathway interactions within cutaneous malignancies

Melanoma and non-melanoma cutaneous malignancies are some of the leading causes of cancer-related death in the United States. Though melanoma is more known to have a high mortality rate, the total mortality per year is nearly equal for between melanoma and non-melanoma skin cancer. Moreover, the non-melanoma types of cutaneous malignancies have potential to become locally invasive and even metastasize with very little to no treatment options when advanced. The development of these malignancies involves various genetic pathways through the four hallmarks of cancer development: malignant cell growth, apoptosis evasion, the use of supporting stroma and vascularization, and modulating and promoting an inadequate immune response. The genetic signaling pathways of basal cell carcinoma, squamous cell carcinoma, verrucous carcinoma, basosquamous cell carcinoma, melanoma, and cutaneous T-cell lymphoma interact with each other through genetic predisposition as well as with environmental exposures. Furthermore, solar ultraviolet radiation and chronic inflammatory states are found to initiate the progression of many of these cutaneous malignancies. This paper includes validated models of genetic pathways, emerging pathways, and crosstalk between genetic pathways through the four hallmarks of cancer development. Moreover, unlike most reviews addressing oncogenetics of the well-recognized, as well as newly discovered, genetic pathway mutations, this review stresses that these pathways are not fixed but rather exist in dynamic, interrelated, interactive, complex, and adaptive flux states.