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Targeted Therapy Against the Cell of Origin in Cutaneous Squamous Cell Carcinoma

College of Medicine and Public Health, Flinders University, Adelaide, SA 5001, Australia
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC 3000, Australia
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(9), 2201;
Received: 17 April 2019 / Revised: 29 April 2019 / Accepted: 29 April 2019 / Published: 5 May 2019
(This article belongs to the Special Issue Molecular Aspects of Cutaneous Squamous Cell Carcinoma)
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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. View Full-Text
Keywords: Squamous cell carcinoma; cell of origin; differentiated cells; stem cells; cancer stem cells; therapeutic targets Squamous cell carcinoma; cell of origin; differentiated cells; stem cells; cancer stem cells; therapeutic targets

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Goldie, S.J.; Chincarini, G.; Darido, C. Targeted Therapy Against the Cell of Origin in Cutaneous Squamous Cell Carcinoma. Int. J. Mol. Sci. 2019, 20, 2201.

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