Solid organ transplantation can be life saving. However, immuno suppression necessary to prevent rejection increases the incidence of cutaneous squamous cell carcinomac SCC fold, Current treatments for solid organ transplant recipients SOTRs are largely surgicalwhich can be disfiguring and impact quality of lifeThere is a huge need for a safe and effective chemoprevention agent for cSCC in SOTRsThe RAF MEK ERK signaling pathway plays a key role in cSCC tumorigenesisThereforewe identified a novel softmetabolically labile MEK inhibitor NFX which we have formulated into a stable topical gel We have demonstrated in minipigs and rodents that topical NFX inhibits p ERKa downstream biomarker of RAS MAPK signaling in the skin but is efficiently cleared from circulationthereby minimizing systemic toxicities observed with oral MEK inhibitors We have demonstrated that topical NFXis an effective chemo prevention agent in a well established UV driven mouse model of cSCC We are seeking funding to aetermine if a. topical NFX gel penetrates human cSCC explants and b. evaluate the durability of the chemoprevention response in the cSCC mouse model Data from these studies will support advancement into a clinical trial to evaluate topical NFXas chemopreventive agent in SOTRs
