Resistance to SMO Inhibitors in Advanced Basal Cell Carcinoma: A Case Highlighting the Role of Molecular Tumor Profiling.

ABSTRACT: Basal cell carcinoma (BCC) is the most common skin cancer, predominantly affecting sun-exposed areas. It typically grows slowly and rarely metastasizes, though untreated cases can cause significant tissue destruction and morbidity. Its pathogenesis primarily involves dysregulation of the Hedgehog (HH) signaling pathway, mainly through mutations in PTCH1 or SMO genes, leading to chronic activation of downstream GLI transcription factors. Accordingly, current targeted therapies for locally advanced, unresectable, or metastatic BCC focus on SMO inhibition, using orally administered drugs such as vismodegib and sonidegib. Although these therapies have shown success, many patients develop resistance, with about 50% harboring mutated SMO. In numerous cases, genetic determinants (so

SUBMITTER: Papaccio F 

PROVIDER: S-EPMC12785518 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature