Abstract and Introduction
Actinic keratosis (AK) is a common precancerous condition found on chronically sun-damaged skin, particularly on the face, scalp, arms, and legs. Early and effective treatment of AKs is important to prevent progression to squamous cell carcinoma. Many topical treatments for AKs are often limited because of poor tolerability, prolonged treatment duration, and reduced adherence. Tirbanibulin 1% ointment, a new topical field therapy for AKs, reduces these issues. It requires a consecutive 5-day application period and is effective, demonstrating complete (100%) clearance of AK lesions in 49% of patients, partial (>75%) clearance in 72%, and a median reduction in lesion count of 87.5% while exhibiting a favorable safety profile, mild adverse events, improved tolerability, and long-term results.
Actinic keratosis (AK) is a common, recurrent precancerous condition found on chronically sun-damaged skin, particularly on the face, scalp, arms, and legs. Clinically AKs appear as macules, papules, or hyperkeratotic plaques with an erythematous background. Its prevalence steadily increases with age and prolonged sun-exposure. The American Academy of Dermatology (AAD) notes that approximately 60% of predisposed individuals over the age of 40 are diagnosed with at least one AK. Other risk factors include male gender, fair skin (Fitzpatrick type I-II), ultraviolet (UV) exposure, immunosuppression, previous history of AKs or skin cancer, human papillomavirus (HPV) infection, and genetic diseases.
Cumulative UV exposure is considered a major risk factor for AK development because of the resultant modification of cellular repair mechanisms in keratinocytes. UVB irradiation causes the formation of thymidine dimers in DNA and mutations of the telomerase gene, whereas UVA indirectly induces DNA mutation through photo-oxidative stress. The clinical significance of AKs is secondary to the associated discomfort, cosmetic burden, and the possibility of progression to invasive squamous cell carcinoma (SCC). Rates of malignant transformation vary from 0.025% to 16%, and the risk of progression increases in patients with multiple AKs (more than five). While AKs are a risk factor for the development of SCC, it is impossible to predict which lesions will transform, therefore treatment of all AKs is recommended.
Many treatments exist for AKs. Single or few discrete AKs are typically treated with cryosurgery. Treatment of multiple lesions and surrounding photo-damaged skin (field cancerization) includes topical agents and photodynamic therapy (Table 1). These treatments may be associated with local skin reactions of pain, irritation, redness, flaking, erosions, ulcerations, and irreversible skin changes of pigmentation and scarring. Furthermore, some treatments have to be administered over periods of weeks or months, which may reduce adherence and undermine treatment success.
More recently, the role of the Src kinase in carcinogenesis has shed light on an alternative therapeutic option. In UV damaged skin, a cascade of events activates peroxisome proliferator activated receptor (PPAR) beta/delta which stimulates the Src oncogene expression, increases Src kinase activity and enhances the EGFR/Erk1/2 signaling pathway, resulting in increased epithelial-to-mesenchymal transition (EMT) marker expression. Elevated levels of Src have been linked to AKs and SCCs, and play a role in both primary tumor growth and metastases. Therefore, Src inhibitors were viewed as a plausible therapeutic option and many have since been developed. Tirbanibulin is a novel compound that inhibits Src kinase signaling and tubulin polymerization in rapidly dividing cells. It has shown promise as a new therapeutic agent for the treatment of AKs on the face or scalp.
Skin Therapy Letter. 2022;27(4):4-7. © 2022 SkinCareGuide.com