Emerging precision diagnostics in advanced cutaneous squamous cell carcinoma

Abstract

Advanced cutaneous squamous cell carcinoma (cSCC) encompasses unresectable and metastatic disease. Although immune checkpoint inhibition has been approved for this entity recently, a considerable proportion of cases is associated with significant morbidity and mortality. Clinical, histopathological, and radiological criteria are used for current diagnostics, classification, and therapeutic decision-making. The identification of complex molecular biomarkers to accurately stratify patients is a not yet accomplished requirement to further shift current diagnostics and care to a personalized precision medicine. This article highlights new insights into the mutational profile of cSCC, summarizes current diagnostic and therapeutic standards, and discusses emerging diagnostic approaches with emphasis on liquid biopsy and tumor tissue-based analyses.

Recent Trends in the Integrated Management of Cutaneous Squamous Cell Carcinoma

“…Precision medicine using liquid biomarker analysis of circulating tumor cells, circulating tumor DNA, proteomic plasma profiling, or miRNA can potentially improve the risk-stratification strategies in these problematic cases. The future focus should be on this novel biomarker's analysis to supplement the current tissue-based diagnostic standards [108].…”

The role of micrometastasis in high‐risk skin cancers

“…These insights are forcing a change in how clinicians view carcinogenesis 2,5,10 . It is now evident that most cancers, including skin cancers, generate micrometastases far earlier than previously thought 11–14 . Both vascular and lymphatic seeding can occur before there is clinical evidence of a primary tumour, 3,5,15 and it is now clear that these two compartments of passage have different, but inter‐dependant roles in facilitating distal metastasis 6–8 .…”

Cancer-Derived Extracellular Vesicles as Biomarkers for Cutaneous Squamous Cell Carcinoma: A Systematic Review

“…While typically remediable with prompt surgical removal, the sheer number of patients diagnosed with cSCC results in a substantial number of cSCC-related death [ 4 , 5 ]. The mutational landscape and risk factors beyond ultraviolet radiation of cSCC are not yet fully investigated, which may affect clinical decisions in precision medicine [ 6 , 7 ]. This is further complicated by the heterogeneity of tumor cells across time and subpopulations identified in traditional genetic analysis on tissue biopsies [ 8 , 9 ].…”