Squamous Cell Carcinoma: Biomarkers and Potential Therapeutic Targets

Abstract

Squamous cell carcinoma (SCC) is the second most frequent non-melanoma skin cancer (NMSC) and carries with it a significant psychosocial and economic burden for both patients and health-care systems. Known risk factors for SCC include chronic ultraviolet (UV) exposure, chronic wounds and inflammation, exposure to certain chemicals and immunosuppression. The considerable risk of SCC recurrence and metastasis has driven the need for the discovery of new molecules that could explain the initiation and biological behavior of this type of NMSC. In this respect, proteomic research techniques have rapidly evolved and adapted in order to connect missing links and single out distinctive skin cancer biosignatures. Proteomic analysis of normal, dysplastic, and malignant keratinocytes appears to be promising in respect to SCC biomarker discovery, with the potential to aid in risk assessment, early detection, disease progression and development of novel targeted therapeutic agents. Identifying changes in the keratinocyte proteome pattern from normal to inflammatory and malignant cells will lead to the discovery of novel SCC biomarkers that could represent valuable tools for patient screening, diagnosis, management and follow-up.

The Role of Beta HPV Types and HPV-Associated Inflammatory Processes in Cutaneous Squamous Cell Carcinoma

“…The tumour is mainly diagnosed in middle-aged and older adults, the young individuals being less frequently affected. In some cases, cSCC exhibits an aggressive behaviour with a significant risk of metastasis [1,2]. Its pathogenesis remains incompletely elucidated; however, several risk factors have been identified.…”

Mediators of Inflammation in Topical Therapy of Skin Cancers

“…Its antiangiogenic activity is based on the ability to increase the secretion of IL-10 and IL-12 but also IFN's ability to decrease cellular production of some proangiogenic factors like b-FGF, IL-8, and urokinase plasminogen activator, to inhibit vascular motility and invasion, and to induce endothelial cell apoptosis [59]. Moreover, IP-10, the interferon-inducible protein 10, has an angiostatic effect [59, 60]. IL-12 inhibits endothelial proliferation and tube formation in vitro and angiogenesis in vivo , by upregulating IFN- γ , decreasing the production of VEGF and b-FGF (fibroblast growth factor), and inhibiting endothelial migration and invasion [59, 61].…”

Modulation of the activity of certain genes involved in tumor cell metabolism in the presence of the cytotoxic peptides defensin and cathelicidin LL37

“…This explains the increase of XBP gene expression in the HT29 cells, whose fight for survival was fiercer. ER stress may be a potential target for the development of new cancer therapy able to reduce adaptation to hypoxia, inflammation and angiogenesis of tumor cells, so that resistance to cytostatic therapy may be prevented (9)(10)(11)(12)(13)(14).…”