The transcriptional landscape analysis of basal cell carcinomas reveals novel signalling pathways and actionable targets

Basal cell carcinoma (BCC) is the most common skin cancer and human malignancy. Although most BCCs are easily managed, some are aggressive locally, require Mohs micrographic surgery, or can even metastasize. In the latter, resistance to Sonic Hedgehog inhibitors may occur. Despite their frequent occurrence in clinical practice, their transcriptional landscape remains poorly understood. By analyzing BCC RNA sequencing data according to clinically important features (all BCCs versus normal skin, high-risk versus low-risk BCCs based solely on histopathological subtypes with aggressive features, advanced versus non-advanced BCCs, and vismodegib-resistant versus vismodegib-sensitive tumors), we have identified novel differentially regulated genes and new targetable pathways implicated in BCC tumorigenesis. Pathways as diverse as IL-17, TLR, Akt/PI3K, cadherins, integrins, PDGF, and Wnt/beta-catenin are promising therapeutic avenues for local and systemic agents in managing this common malignancy, including through drug repurposing of existing medications. We experimentally validated several of these targets as biomarkers in our patient-derived cohort of primary BCC tumors.

Automated summary

Basal cell carcinoma is the most common skin cancer, but still poses challenges in treatment. By analyzing RNA sequencing data, new therapeutic avenues and potential targets have been identified, providing new insights for treating BCC.