A Review of Existing Therapies for Actinic Keratosis: Current Status and Future Directions

Abstract

Actinic keratosis (AK) is a chronic skin disease in which clinical and subclinical cutaneous lesions coexist on sun-exposed areas such as the head and neck region and the extremities. The high prevalence of AK means the disease burden is substantial, especially in middle-aged and elderly populations. Evidence indicates that AK may progress into invasive cutaneous squamous cell carcinoma, so the European guidelines recommend treatment of any AK regardless of clinical severity. Given the aging population and therefore the increasing incidence of AK and cutaneous field carcinogenesis, further updates on the long-term efficacy of current therapies and new investigational agents are critical to guide treatment choice. Patients often have difficulty adequately applying topical treatments and coping with adverse local skin reactions, leading to less than optimum treatment adherence. The development of associated local skin symptoms and cosmetic outcomes for the area of interest are also relevant to the choice of an appropriate therapeutic strategy. Treatment is always individually tailored according to the characteristics of both patients and lesions. This review focuses on the therapeutic approaches to AK and illustrates the currently available home-based and physician-managed treatments.

Oral mTOR Inhibition Limits And Reduces Actinic Keratosis And Cutaneous Squamous Cell Carcinoma In A UVB-Induced Mouse Model

“…Ideally, actinic keratosis treatment should remove as many clinical and subclinical lesions as possible, achieve a long-lasting clinical remission, produce a pleasing cosmetic outcome, and stop the development of invasive squamous cell carcinoma 53 . Current standards of care for AK patients rely on lesion-directed procedures or topical field therapies.…”

Topical N‐phosphonacetyl‐l‐aspartate is a dual action candidate for treating non‐melanoma skin cancer

“…All three topical treatments are FDA-approved for AK and have reported response rates of 40%-80% for AKs, with 5-FU being most effective. 9 5-FU and IMQ are also FDA-approved to treat superficial BCC, and studies have shown therapeutic effects when applied to the treatment of superficial SCC. 10 Although each of these topical agents can treat multiple, diffuse lesions (thereby addressing the 'field cancerization' problem) and often result in an overall higher rate of long-term clearance than cryotherapy, each is also associated with an intense local skin reaction characterised by pain, burning, skin erosions and, in some instances, hyper-or hypopigmentation of the skin.…”

“…To address the high statistical risk of cancer arising within these regions, several non‐invasive topical treatments are currently approved, including fluorouracil (5‐FU; an antimetabolite), imiquimod (IMQ; an immunomodulator), and tirbanibulin (a microtubule inhibitor). All three topical treatments are FDA‐approved for AK and have reported response rates of 40%–80% for AKs, with 5‐FU being most effective 9 . 5‐FU and IMQ are also FDA‐approved to treat superficial BCC, and studies have shown therapeutic effects when applied to the treatment of superficial SCC 10 .…”

Efficacy and safety of tirbanibulin 1% ointment in actinic keratoses: Data from two phase‐III trials and the real‐life clinical practice presented at the European Academy of Dermatology and Venereology Congress 2022

“…Areas of the skin often affected include the face (especially the nose and forehead), the forearms and backs of hands, on the rims of the ears and bald scalps in men and on the legs below the knees in women 5 . Populations frequently impacted by AKs include the elderly who in addition to cumulative sun exposure also have higher rates of co‐morbidities and polymedication that may interfere with treatment 8,9 …”