Squamous Cell Carcinoma

Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers, with an estimated 700,000 cases diagnosed in the United States annually. Risk factors for cSCC include older age, male gender, fair pigmentation, ultraviolet exposure, and immunosuppression. In particular, solid organ transplant recipients (SOTRs) have a 65–250 fold increased incidence of immunosuppressant-mediated cSCC compared to the general population and up to 3.2% of SOTRs die from cSCC.

700.000 cases

NFlection is developing a topical gel formulation of a proprietary “soft” (metabolically labile) MEK inhibitor as a chemopreventive agent for cSCCs in SOTRs. Previous studies have demonstrated the key role of the Ras/Raf/MEK/ERK signaling pathway in cSCCs. Recently, Dr. Kenneth Tsai and colleagues at the Moffitt Cancer Center demonstrated that systemic administration of two MEK inhibitors, trametinib and cobimetinib, could prevent the formation of cSCC in a UV-irradiated mouse model of cSCC. Topical application of an NFlection disovered MEK inhibitor in the same UV-irradiated mouse model similarly suppressed the development of new cSCCs without any systemic toxicity.

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NFlection has also tested a “soft” topical MEK inhibitor ex vivo in human cSCC explants and has demonstrated suppression of pERK, a biomarker of Ras/Raf/MEK/ERK pathway activation, when applied to the surface of the skin. The MEK inhibitor delivered by this formulation can penetrate into the dermis and epidermis layers of the skin to locally deliver the MEK inhibitor as a chemopreventive agent. The soft topical MEK inhibitor rapidly degrades upon reaching systemic circulation to minimize the side effects caused by systemic exposure to MEK inhibitors.