[Cutaneous epithelial tumors. Molecular biology and pathogenesis-based therapy]

Basal cell carcinomas and squamous cell carcinomas are the most common human cancers and increasing in incidence. The development of novel, pathogenesis-based therapies requires a better knowledge of the molecular mechanisms leading to the development of these tumors. Basal cell carcinomas are characterized by aberrant activation of Sonic-Hedgehog (SHH) signaling due to mutations in the PTCH or SMOH genes. In addition, about 50% of the cases carry mutations in the TP53 tumor suppressor gene. Squamous cell carcinomas lack alterations of SHH signaling, while TP53 mutations are detectable in virtually all cases. Alterations in cell cycle regulatory genes, such as CDKN2A, are also common. Recently, specific inhibitors of the SHH-signaling pathway have been developed and shown promising results in preclinical studies on experimental basal cell carcinomas. However, the clinical significance of such targeted molecular therapy remains to be evaluated. Another successful pathogenesis-based therapy, which is already in clinical use, is the administration of topic immune response modifier imiquimod. This drug can eradicate non-melanoma skin cancers by different mechanisms, including cytokine-mediated stimulation of the anti-tumor immune response, as well as the induction of tumor cell apoptosis.