Current developments in pharmacotherapy for actinic keratosis

ABSTRACT

Introduction: Actinic keratosis (AK) is a superficial squamous cell carcinoma (SCC) where chronic sun exposure playing central role in its pathogenesis. UVB causes direct damage to DNA, producing pyrimidine dimers, and suppressing the protective role of p53. The stepwise progression of AK, with increased expression of anti-apoptotic Bcl-2, favors progression to SCC. Moreover, the dermal response characterized by inflammation and mediated by prostaglandins is a critical component of tumorigenesis that promotes tumor growth, tissue invasion, angiogenesis and metastasis. Other risk factors are represented by age, gender, phototype and drugs.

Areas covered: In this review, the authors document the recent developments of different therapies used to treat AK and provide their perspectives on current and future treatment strategies.

Expert opinion: The usefulness of long-term treatment with piroxicam and sun filters or diclofenac targeting the inflammation phases of skin tumorigenesis favors AK’s healing and provides greater control of the cancerization field. Nonsteroidal anti-inflammatory drugs can be safely used in patients who use photosensitizing drugs and, therefore, are more at risk of developing skin tumors. Immunomodulatory therapies, which require shorter treatment, are characterized by more common local side effects, and need more attention by the dermatologist in the concern of patient education, resulting essential to improve adherence and outcomes.

KEYWORDS:

• Actinic keratosis
• non-melanoma skin cancers
• antimetabolites
• immunomodulators
• antinflammatory drugs
• ablative therapies

Article Highlights

• In this article the authors have pointed out that even in patients affected by actinic keratoses and extensive photodamage, intended as a cancerization field, the dermatologist must aim at a personalized therapeutic approach in the interest of the patient, his comorbidities, the type of lesion and of his expectations.

• The main target therapies and those of the cancerization field must be interpreted as therapies that can intervene in the different pathogenetic phases of actinic keratoses, and can therefore restore the pre-existing local immune conditions.

• The inflammation at the cutaneous level, as happens in the other organs, is a key phase that leads slowly to the irreversible phases of tumorigenesis and therefore it is correct and necessary to use the anti-inflammatory molecules both in the prevention and in the treatment of actinic keratoses.

• Furthermore, one of the immediate aspects of using these molecules is the disappearance of pain for patients.

• Another aspect that is underlined is the possibility of combining therapies for actinic keratoses, at different times according to the features lesions and the state of the patients, based above all on the drugs they take and on their lifestyle.

• Immunotherapies that are used for short periods are very effective and in those cases the patient must be followed at all stages of treatment to avoid suspending therapy.

• Long-term therapies with anti-inflammatories by reducing inflammation over time also control the progression of subclinical lesions.

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.