Clinical, Cosmetic and Investigational Dermatology (Nov 2022)
Tirbanibulin for Actinic Keratosis: Insights into the Mechanism of Action
Abstract
Todd Schlesinger,1 Eggert Stockfleth,2 Ayman Grada,3 Brian Berman4 1Clinical Research Center of the Carolinas, Charleston, SC, USA; 2Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum, Bochum, Germany; 3Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 4Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USACorrespondence: Ayman Grada, Email [email protected]: Actinic keratosis (AK) is a common pre-neoplastic skin lesion constituted by uncontrolled proliferation of atypical keratinocytes that may evolve to squamous cell carcinoma. With global prevalence increasing, AK is expected to be the most common carcinoma of the skin. Tirbanibulin is a reversible tubulin polymerization inhibitor with potent anti-proliferative and anti-tumoral effects. In-vivo and in-vitro studies have shown that tirbanibulin significantly inhibits cell proliferation, tumor growth and downregulates Src signaling with no overt toxicity. Early phase and Phase III trials have shown high lesion clearance, compliance, and few side effects of once daily tirbanibulin treatment. This review discusses tirbanibulin anti-cancer activity, focusing on tubulin polymerization and Src signaling inhibitory effects, highlighting relevant literature and novel preclinical results from the ATNXUS-KX01-001 study. Furthermore, we address the relevant findings obtained in recent clinical trials to evaluate the safety, efficacy, pharmacokinetics, clearance efficacy, and side effects of the 1% tirbanibulin ointment applied once daily. In summary, we highlight preclinical and clinical evidence on the use of tirbanibulin as an effective and safe treatment option for AK.Keywords: actinic keratosis, tirbanibulin, microtubules, Src kinase inhibitor
