Solid organ transplantation can be life" saving. However, immunosuppression necessary to preventrejection increases the incidence of cutaneous squamous cell carcinoma (cSCC) 65-250 fold. Currenttreatments for solid organ transplant recipients (SOTRs) are largely surgical, which can be disfiguring andimpact quality of life. There is a huge need for a safe and effective chemoprevention agent for cSCC inSOTRs. The RAF"ÂMEK"ÂERK signaling pathway plays a key role in cSCC tumorigenesis. Therefore, we identifieda novel soft (metabolically labile) MEK inhibitor, NFX"Â179, which we have formulated into a stable, topical gel.We have demonstrated in minipigs and rodents that topical NFX"Â179 inhibits p"ÂERK (a downstream biomarkerof RAS/MAPK signaling) in the skin but is efficiently cleared from circulation, thereby minimizing systemictoxicities observed with oral MEK inhibitors. We have demonstrated that topical NFX"Â179 is an effectivechemoprevention agent in a well"Âestablished UV"Âdriven mouse model of cSCC. We are seeking funding to (a)determine if topical NFX"Â179 gel penetrates human cSCC explants and (b) evaluate the durability of thechemoprevention response in the cSCC mouse model. Data from these studies will support advancement into aclinical trial to evaluate topical NFX"Â179 as chemopreventive agent in SOTRs.
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