TOPIC 386: PROOF OF CONCEPT FOR A TOPICAL MEK INHIBITOR AS A CHEMOPREVENTIVE AGENT FOR SQUAMOUS CELL CARCINOMA IN HIGH RISK ORGAN TRANSPLANT PATIENTS

Solid organ transplantation can be life savingHoweverimmunosuppression necessary to prevent rejection increases the incidence of cutaneous squamous cell carcinomacSCCfoldCurrent treatments for solid organ transplant recipientsSOTRsare 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 labileMEK inhibitorNFXwhich we have formulated into a stabletopical gelWe have demonstrated in minipigs and rodents that topical NFXinhibits p ERKa downstream biomarker of RAS MAPK signalingin the skin but is efficiently cleared from circulationthereby minimizing systemic toxicities observed with oral MEK inhibitorsWe have demonstrated that topical NFXis an effective chemoprevention agent in a well established UV driven mouse model of cSCCWe are seeking funding toadetermine if topical NFXgel penetrates human cSCC explants andbevaluate the durability of the chemoprevention response in the cSCC mouse modelData from these studies will support advancement into a clinical trial to evaluate topical NFXas chemopreventive agent in SOTRs