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Srcasm Levels: Potential Therapeutic Target in Skin Cancer

By: Cordi Craig
Posted: Thursday, January 3, 2019

A new study, published in the Journal of Investigative Dermatology, suggested that small molecules that increase levels of Srcasm, a negative regulator of Src-family tyrosine kinases and EGFR, may prove to be effective in the treatment of cutaneous squamous cell carcinomas. Vivian Lee, MD, of the University of Pennsylvania, Philadelphia, and colleagues shared their preclinical findings of the molecular pathways that regulate the formation of cutaneous squamous cell carcinomas, with clinical implications for a precision medicine approach to treating such lesions.

The authors used K14-Fyn Y528F transgenic mice that developed cutaneous squamous cell carcinoma after approximately 6 weeks of age. The mice received doxycycline to induce Srcasm levels after the disease formed. The induction of Srcasm was correlated with a complete regression of the disease and “normalization of oncogenic biomarkers.” The authors believe that Srcasm modulated tyrosine kinase signaling in keratinocytes, which promoted differentiation and prevented the formation of new cancerous growth.

The K14-Fyn Y528F transgenic mice developed precancerous lesions and cutaneous squamous cell carcinoma with a biomarker profile similar to human lesions; the authors hope that it may be used as a screening tool to identify topical small-molecule kinase inhibitors that induce cancer regression. Recent studies using mice that are not treated with Srcasm seem to confirm the observations in transgenic mice and provide additional support for its potential role.

“Together, these data support the hypothesis that topical small molecules that can upregulate Srcasm levels may be useful for treating [cutaneous squamous cell carcinoma],” the authors concluded.

Disclosure: The study authors reported no conflicts of interest.



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