Abstract
The prevalent keratinocyte-derived neoplasms of the skin are basal cell carcinoma and squamous cell carcinoma. Both so called nonmelanoma 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 have begun to pave the way for modulating new molecular targets therapeutically with small molecules.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Carcinoma, Basal Cell / genetics*
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Carcinoma, Basal Cell / metabolism
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Carcinoma, Basal Cell / pathology
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Carcinoma, Squamous Cell / genetics*
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology
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Clinical Trials as Topic
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Cyclin-Dependent Kinase Inhibitor p16 / genetics
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Cyclin-Dependent Kinase Inhibitor p16 / metabolism
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Gene Expression Regulation, Neoplastic*
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Humans
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism
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Organ Specificity
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Patched Receptors
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Patched-1 Receptor
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-fyn / genetics
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Proto-Oncogene Proteins c-fyn / metabolism
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Proto-Oncogene Proteins p21(ras)
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism
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Signal Transduction / genetics*
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Skin Neoplasms / genetics*
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Skin Neoplasms / metabolism
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Skin Neoplasms / pathology
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Smoothened Receptor
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Ultraviolet Rays
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ras Proteins / genetics
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ras Proteins / metabolism
Substances
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Cyclin-Dependent Kinase Inhibitor p16
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KRAS protein, human
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Neoplasm Proteins
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PTCH1 protein, human
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Patched Receptors
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Patched-1 Receptor
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Proto-Oncogene Proteins
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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SMO protein, human
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Smoothened Receptor
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FYN protein, human
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Proto-Oncogene Proteins c-fyn
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Proto-Oncogene Proteins p21(ras)
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ras Proteins