Overview of genetic signaling pathway interactions within cutaneous malignancies

Abstract

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 dynamic, interrelated, interactive, complex, and adaptive flux states.

Pathophysiology, Histopathology, and Differential Diagnostics of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma—An Update from the Pathologist’s Point of View

“…Increased cyclin D1 gene expression was observed in the precursor lesions of cSCC-AK and BD-and in primary cSCC. The cyclin D1 marker can be used as a prognostic marker in the diagnosis and treatment of cSCC [44][45][46][47][48].…”

“…Given that NOTCH family gene defects are inactivation defects, they are thought to be tumor suppressor genes. The Wnt/β-catenin pathway is also affected by NOTCH1 gene mutation as this pathway is involved in oncogenesis [6,[45][46][47]. The TP63 gene that encodes the p63 protein is also part of the category of p53 transcription factors; it is involved in the pathogenesis of cSCC and interferes with the processes of cell proliferation, differentiation, and senescence.…”

Cutaneous Squamous Cell Carcinoma: An Up-to-Date Comprehensive Review with a Focus on Contemporary Optical Imaging Diagnostic Modalities

“…Risk factors for cSCC are male gender, Fitzpatrick skin types I-III, age over 50, UV radiation exposure, immunosuppression, human papillomavirus (HPV) [23] infection, chronic wounds, environmental exposures, and familial cancer syndromes [14]. Environmental agents causing cSCC include arsenic-contaminated well water [24,25], insecticides with lead arsenate, aromatic polycyclic hydrocarbons (e.g., tar, terrain, and ash), nitrosamines, and alkylating agents [26,27]. Exposure to ionizing radiation, even in limited quantities, has also been linked with more aggressive forms of cSCC (10-30%) [28,29].…”

Drug Delivery Strategies for Avobenzone: A Case Study of Photostabilization

“…On the other hand, UV rays help improve human health by facilitating vitamin D and endorphin synthesis in the skin. Nevertheless, excessive exposure to UV rays causes atrophy, wrinkling, pigmentary changes, and even cancer [ 13 ]. Each year, many people worldwide are diagnosed with various types of skin cancers.…”