Actinic keratosis (AK) is a skin disease marked by irregular keratinocyte proliferation in areas that have historically undergone chronic ultraviolet (UV) radiation exposure. Protheragen is dedicated to advancing the field of actinic keratosis (AK) diagnostics and therapeutics. Our services encompass a wide range of offerings, from histopathological examination and advanced imaging techniques to the development and testing of therapeutics.
Overview of Actinic Keratosis (AK)
Actinic keratosis (AK), or solar keratosis, is a common skin disorder causing scaly, red, and thickened patches, which are papular in nature, particularly on the face, neck, and the dorsal surface of hands that are exposed to the sun. It is well accepted that AK precedes cutaneous squamous cell carcinoma (SCC) and, if untreated, may progress to invasive cancers. The risk of sustaining AK is directly linked to the total lifetime ultraviolet (UV) exposure and is particularly high among individuals with lighter skin, thus categorized as Type (Fitzpatrick) I or II. The disease is caused by ultraviolet (UV) radiation in the form of sun exposure, which leads to skin cancer, and a critical mutation, particularly in the gene p53, that controls the unregulated growth of keratinocytes.
Fig.1 A comprehensive overview of the onset and development of actinic keratosis lesions. (Arcuri D.,
et al., 2023)
Pathogenesis of Actinic Keratosis (AK)
The primary and most important cause of AK is almost continuous exposure to ultraviolet (UV) radiation of the type and specifically UVB (280-315 nm), which damages the DNA of keratinocytes. UVB radiation causes the formation of thymidine dimers in DNA, which are mutagenic, particularly to the oncogene suppressant p53. Such damage is capable of causing uncontrolled cell division of dysplastic keratinocytes, which contributes to AK and eventually SCC. Other contributory factors include immunosuppression (for example, in organ transplant patients), exposure to arsenic, and chronic use of sunbeds. Further complicating the disease’s multifactorial nature, some types of human papillomavirus HPV have also been associated with human AK.
Diagnostics Development for Actinic Keratosis (AK)
- Histopathological Examination
The histopathological examination is essential in the diagnosis of AK. An AK biopsy shows distinctive features of epithelial dysplasia, which may be graded from mild to severe and may extend trans the basal layer to the full thickness of the epidermis. Hypertrophic, bowenoid, lichenoid, acantholytic, and pigmented types are also considered histological variants of AK. Such meticulous histological examination helps in the differential diagnosis of AK and other skin diseases and is helpful in assessing the degree of dysplasia.
- Advanced Imaging Techniques
Newer imaging modalities such as dermatoscopy, reflectance confocal microscopy, and high-definition optical coherence tomography are now being used to visualize and monitor the progression of AK lesions. These modalities are useful in removing and distinguishing AK from other skin disorders much earlier than other methods, which are more invasive than the methods of Histopathological examination. One example is the dermatoscope that enables detailed examination of skin lesions, which makes it possible to look for distinct features of AK.
Therapeutics of Actinic Keratosis (AK)
| Therapeutics |
Drug Name |
Mechanism |
Description |
Stage |
| Chemoprophylaxis |
Nicotinamide |
Enhances DNA repair, reduces UV-mediated inflammation, and protects against UV-induced immunosuppression |
Oral or topical administration to prevent AK formation |
Approved |
| Chemoprophylaxis |
Acitretin |
Normalizes keratinocyte differentiation and reduces pro-inflammatory cytokines |
Oral administration, especially in immunocompromised patients |
Approved |
| Chemoprophylaxis |
Topical 5-Fluorouracil (5-FU) |
Inhibits thymidylate synthase, inducing apoptosis in rapidly dividing cells |
Topical application for chemoprevention |
Approved |
| Topical Therapy |
5-FU |
Inhibits thymidylate synthase, inducing apoptosis in rapidly dividing cells |
5% cream applied twice daily for 2-4 weeks |
Approved |
| Topical Therapy |
Imiquimod |
Stimulates immune response via Toll-like receptors, inducing apoptosis |
5% cream applied 3 times weekly for 12-16 weeks |
Approved |
| Topical Therapy |
Diclofenac |
Inhibits COX-1 and COX-2, reducing inflammation and promoting immune-mediated clearance |
3% gel applied twice daily for 30-90 days |
Approved |
| Topical Therapy |
Tirbanibulin |
Microtubule and Src kinase inhibitor induce apoptosis |
1% ointment applied daily for 3-5 days |
Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers a wide array of services related to AK diagnostics and therapeutics development, including biomarker discovery and validation, preclinical drug screening and evaluation, and custom assay development. Our services are designed to support the entire research continuum, from early-stage discovery to late-stage preclinical development, providing clients with the tools and expertise needed to advance their AK research programs and bring novel diagnostics and therapeutics to market.
- Primary Keratinocyte Cultures
- Immortalized Keratinocyte Cell Lines
- UV-B Irradiation Models
- DMBA (7,12-dimethylbenz[a]anthracene) / TPA (12-O-tetradecanoylphorbol-13-acetate) Induced Models
Protheragen understands that each client has distinct research needs, which is why we offer tailored services designed to achieve specific research goals. Whether it's developing custom assays for biomarker validation or designing specialized preclinical studies to assess innovative therapeutic targets, our team collaborates closely with clients to ensure their objectives are met with accuracy and effectiveness. If you are interested in our services, please feel free to contact us.
References
- Arcuri, Domenico, et al. "Pharmacological agents used in the prevention and treatment of actinic keratosis: a review." International Journal of Molecular Sciences 24.5 (2023): 4989.
- Malvehy, Josep, et al. "Actinic keratosis: Current challenges and unanswered questions." Journal of the European Academy of Dermatology and Venereology 38 (2024): 3-11.
- De Berker, David, et al. "Guidelines for the management of actinic keratoses." British Journal of Dermatology 156.2 (2007): 222-230.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
