Skin cancer is the most common form of cancer in the United States, and 20% of adults who live to age 70 will develop some form of it. Squamous cell carcinoma (SCC) is the second most common type of skin cancer, with 1 million people receiving diagnoses each year.
SCC differs from other skin cancers in that it can spread to organs and tissues beyond the skin, including the neighboring lymph nodes and bones. Once it involves parts of the body other than the skin, SCC becomes challenging to treat. Conversely, the condition is relatively easy to treat when caught early.
Contrary to popular belief, SCC is not exclusive to the skin. The stratified epithelial cells from which squamous cells descend can be found in various areas of the respiratory and gastrointestinal tracts, such as the nasal cavity, oropharynx, esophagus, and anogenital region—where tegument or mucosa predominate. In some cases, squamous cell differentiation protects the mucosa by improving tissue integrity. However, abnormal activity or presence of squamous cells can also result in malignancies. Since the squamous cells are not limited to the skin, SCCs can affect other parts of the body such as the cervix, esophagus, and lungs.
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Characterized by highly heterogenous tissue, SCCS manifest in specific cell populations at various stages of differentiation. The fact that these diverse cell populations can change the lineage from which they proliferate, become dormant, or enter slow-cycling growth phases renders monotherapeutic approaches generally ineffective against SCCs.
To that end, scientists have explored the idea of engaging differentiation therapy as a means of preventing SCCs from altering their lineage and forcing them into terminal differentiation. However, recruiting this sort of treatment runs the risk of prolonging the survival of malignant cells while inadvertently encouraging pro-oncogenic evasion as well as resistance to chemotherapeutic intervention.
Organ transplant has been linked to an increased risk of cancer, as SCC in patients who have undergone transplantation procedures are more likely to develop SCC than the general population by 100-fold.
Genetics also contributes to the pathogenesis of SCC—researchers have identified strong associations between genetic mutations with or without altered expression of specific molecules that assist in various stages during which the squamous cells commit to the particular lineage or reach terminal differentiation. Genomic disturbances play an equally important role. New research suggests that abnormal changes in stromal cells may contribute significantly in the SCC pathogenesis by allowing malignant cells to fly under the radar of immune surveillance and promoting resistance to chemotherapy.