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

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.

Local Chemotherapy as an Adjuvant Treatment in Unresectable Squamous Cell Carcinoma: What Do We Know So Far?

“…Squamous cell carcinoma (SCC) is one of the most common malignant tumors affecting the skin. The abnormal and quick growth of keratinocytes in the epidermis, often secondary to ultraviolet or sunlight exposure, is a characteristic of this cancer [ 1 , 2 , 3 ]. SCC involving the head and neck area may be particularly aggressive.…”

Adjuvant therapy for high‐risk cutaneous squamous cell carcinoma: 10‐year review

“…Interestingly, gene expression profiling and tissue of origin have been reported to be important factors for determining in vitro tumor sensitivity to targeted therapy 106,107 . Also, investigations of cell signaling pathways associated with development of cSCC have led to identification of molecules (e.g., PD‐1 and EGFR) being targeted in current systemic therapy for patients with high‐risk cSCC 108,109 .…”

“…Interestingly, gene expression profiling and tissue of origin have been reported to be important factors for determining in vitro tumor sensitivity to targeted therapy. 106 , 107 Also, investigations of cell signaling pathways associated with development of cSCC have led to identification of molecules (e.g., PD‐1 and EGFR) being targeted in current systemic therapy for patients with high‐risk cSCC. 108 , 109 Although immunotherapy and targeted therapy are relatively new treatment modalities for high‐risk cSCC, the available evidence, albeit limited, and ongoing investigations in the cSCC arena corroborate the importance of a multidisciplinary approach for more personalized therapy in high‐risk cSCC.…”

MicroRNA-125b exerts antitumor functions in cutaneous squamous cell carcinoma by targeting the STAT3 pathway

“…Although CSCC usually displays benign clinical behavior and can be cured by surgical excision, about 8% of patients with CSCC develop a recurrence and 5% patients present metastasis within 5 years. The prognosis for metastatic CSCC is poor, and its one-year disease-specific survival is 44-56% [4]. A deeper understanding of the molecular mechanisms underlying the biological behavior of CSCC will provide important clues to improve the CSCC diagnosis and treatment.…”