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Oral mTOR Inhibition Limits And Reduces Actinic Keratosis And Cutaneous Squamous Cell Carcinoma In A UVB-Induced Mouse Model
November 4, 2022
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20 minute read
Spring and our partners often validate the findings of our AI-based conclusions — which are often performed using data from primary cell lines — with gold standard in vivo disease models. In this study, we did so by validating the effects of oral mTOR on actinic keratosis and cutaneous squamous cell carcinoma.
Full manuscript on bioRxiv
Actinic keratosis (AK) is a skin disease that is characterized by clinical and subclinical cutaneous lesions in sun-exposed areas. It is a considerable burden due to its high occurrence in middle-aged and older populations, as well as its propensity to progress to invasive cutaneous squamous cell carcinoma.
The mammalian target of rapamycin (mTOR) pathway is critical in carcinogenesis and tumor development, and it has been shown to be over-activated during skin tumorigenesis, particularly upon ultraviolet (UV) radiation exposure, the key risk factor for AK. However, the ability of mTOR inhibitors to treat AK is not well documented.
Herein, we evaluated the effect of oral mTOR inhibitors in vitro and in vivo and found that mTOR inhibitors lower keratinocyte cell proliferation in vitro and both clear and prevent AK and cutaneous squamous cell carcinoma (cSCC) in a UV-B induced SKH1 hairless mouse model of disease
AUTHORS
Booty MG, Komalo B, Hosny A, Headland SE, Fernandez-Figueras MT, Nguyen AM, Cousin W, Heinrich J, Nicolaisen L, DeVay RM, White B, Elabd C