Molecular Biology of Basal and Squamous Cell Carcinomas

The prevalent keratinocyte-derived neoplasms of the skin are basal cell carcinoma and squamous cell carcinoma. Both so-called non-melanoma skin cancers comprise the most common cancers in humans by far. Common risk factors for both tumor entities include sun exposure, DNA repair deficiencies leading to chromosomal instability, or immunosuppression. Yet, fundamental differences in the development of the two different entities have been and are currently unveiled. The constitutive activation of the sonic hedgehog signaling pathway by acquired mutations in the PTCH and SMO genes appears to represent the early basal cell carcinoma developmental determinant. Although other signaling pathways are also affected, small hedgehog inhibitory molecules evolve as the most promising basal cell carcinoma treatment options systemically as well as topically in current clinical trials. For squamous cell carcinoma development, mutations in the p53 gene, especially UV-induced mutations, have been identified as early events. Yet, other signaling pathways including epidermal growth factor receptor, RAS, Fyn, or p16INK4a signaling may play significant roles in squamous cell carcinoma development. The improved understanding of the molecular events leading to different tumor entities by de-differentiation of the same cell type has begun to pave the way for modulating new molecular targets therapeutically with small molecules.