Abstract
Squamous cell carcinomas (SCC), including cutaneous SCCs, are by far the most frequent cancers in humans, accounting for 80% of all newly diagnosed malignancies worldwide. The old dogma that SCC develops exclusively from stem cells (SC) has now changed to include progenitors, transit-amplifying and differentiated short-lived cells. Accumulation of specific oncogenic mutations is required to induce SCC from each cell population. Whilst as fewer as one genetic hit is sufficient to induce SCC from a SC, multiple events are additionally required in more differentiated cells. Interestingly, the level of differentiation correlates with the number of transforming events required to induce a stem-like phenotype, a long-lived potential and a tumourigenic capacity in a progenitor, a transient amplifying or even in a terminally differentiated cell. Furthermore, it is well described that SCCs originating from different cells of origin differ not only in their squamous differentiation status but also in their malignant characteristics. This review summarises recent findings in cutaneous SCC and highlights transforming oncogenic events in specific cell populations. It underlines oncogenes that are restricted either to stem or differentiated cells, which could provide therapeutic target selectivity against heterogeneous SCC. This strategy may be applicable to SCC from different body locations, such as head and neck SCCs, which are currently still associated with poor survival outcomes.
Highlights
Skin squamous cell carcinoma (SCC) is one of the two most common non-melanoma skin cancers and occurs most frequently in sun-exposed regions of the skin and in immunocompromised patients
Patients with skin SCC may develop multiple lesions and surgical resection can often be extensive and disfiguring, especially around cosmetically sensitive areas. This cancer is usually cured by surgical excision, approximately 8% of patients with skin SCC develop a recurrence and 5% present metastasis within 5 years
Epidermal keratinocytes are continually exposed to a wide range of environmental assaults including ultraviolet (UV) irradiation, chemical carcinogens, infection with human papilloma viruses (HPV) and other pathogens; and are at a high risk of acquiring oncogenic mutations
Summary
Skin squamous cell carcinoma (SCC) is one of the two most common non-melanoma skin cancers and occurs most frequently in sun-exposed regions of the skin and in immunocompromised patients. 250,000 patients per year develop skin SCC in the United States [1]. In Australia, the estimated person-based incidence of SCC is thought to be 271 per 100,000 [2]. Patients with skin SCC may develop multiple lesions and surgical resection can often be extensive and disfiguring, especially around cosmetically sensitive areas. This cancer is usually cured by surgical excision, approximately 8% of patients with skin SCC develop a recurrence and 5% present metastasis within 5 years. In patients with metastatic SCC, the prognosis is very poor, with only 10%–20% surviving more than 10 years [4,5]. There is an urgent clinical need to prevent and treat skin SCC, and this requires a thorough understanding of the mechanisms that initiate this disease at the cellular level
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call