DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for actinic keratosis — screening already-approved drugs against its 38-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleActinic keratosis maps to a 38-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for actinic keratosis is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
MDM4 regulator of p53 (MDM4) — MDM4 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 3~{s}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6Q9Y · 1.2 Å · ligand 7-methoxy-~{N}-[(3~{S})-1-(4-methylphenyl)pyrrolidin-3-yl]-1~{H}-indole-3-carboxamide (HRQ). Experimental structure, not a prediction.
What the evidence adds up to
Actinic keratosis is a common intraepidermal neoplasm of sun-damaged skin, with risk factors including low latitude, outdoor work, light skin, and history of sunburn; the role of the immune system is evident from the frequency of these lesions in transplant patients. There is strong evidence that actinic keratoses can progress to squamous cell carcinoma. In a 2000 study using step sections of biopsy samples initially diagnostic of actinic keratosis from 57 patients (69 lesions), additional diagnostic findings appeared in 23 specimens (33%): 9 (13%) showed squamous cell carcinoma in situ, 3 (4%) basal cell carcinoma, and 2 (3%) invasive squamous cell carcinoma. Variables significantly correlated with discovering cancer on step sections were ulceration on the first level, a clinical diagnosis of skin cancer, and a history of skin cancer diagnosed by biopsy. A 2000 case series described a proliferative subtype of actinic keratosis that had failed conventional treatment with liquid nitrogen and/or 5-fluorouracil; histology showed sheets of dysplastic cells migrating down hair follicles and sweat ducts, and an associated infiltrative squamous cell carcinoma or basal cell carcinoma was found in each of the three cases.
A 2008 randomised open-label study compared 3% diclofenac sodium gel (applied once daily) with 5% imiquimod cream (applied three times a week) for 12 weeks in 49 patients. According to investigator-assessed global improvement, complete response was observed in 12% of the diclofenac group and 22% of the imiquimod group; by patient assessment, complete response was 28% for diclofenac and 23% for imiquimod. No significant differences between the two groups were found (p > 0.05), and the authors concluded that complete remission was very low and that topical treatments with these two drugs were not completely effective. Both treatments were well tolerated, with most adverse events related to skin.
A 2018 review notes that imiquimod suffers from pitfalls of conventional formulation including high dose, poor stability, and more side effects, and that patient acceptance and compliance with conventional treatments are generally poor due to side effects, poor cosmetic outcomes, and high costs. The review states that conventional drug delivery systems have been unsuccessful in improving actinic keratosis and that novel therapeutic approaches are being developed.
What remains missing are adequately powered trials that compare combination therapies or novel drug delivery systems against standard topical treatments, with longer follow-up to capture progression to invasive carcinoma. The proliferative subtype, which appears resistant to standard therapies and may harbour invasive cancer, is not addressed by current topical trial designs. Patient stratification by histological subtype, immune status, and prior treatment failure is absent from the existing comparative evidence.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Dermatology · 2003 · 109 citations
Actinic keratosis: epidemiology and progression to squamous cell carcinoma
AbstractActinic keratoses are a common problem in the population, and one of the most common conditions treated by dermatologists. Risk factors for the development of actinic keratosis are those associated with increased sun exposure and increased susceptibility to sun exposure such as low latitude, working outdoors, light skin, and history of sunburn. The role of the immune system is clear from the frequency of actinic keratoses in transplant patients. There is strong evidence that actinic keratoses can progress to squamous cell carcinoma, underscoring the need to identify and treat patients at risk.
Journal of Dermatological Treatment · 2008 · 52 citations
Comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% imiquimod cream in the treatment of actinic keratosis
AbstractBACKGROUND: Topical diclofenac and imiquimod have been reported to be effective in the treatment of actinic keratosis, but a study to compare these two drugs has not been reported yet. OBJECTIVE: To compare the efficacy and safety of topical 3% diclofenac gel plus hyaluronic acid and 5% imiquimod cream in the treatment of actinic keratosis. METHODS: Forty-nine patients with actinic keratosis were enrolled in this randomized comparative open-label study. Twenty-four patients applied 3% diclofenac gel once a daily to their lesions, while the other 25 patients were treated with a 5% imiquimod cream three times a week for 12 weeks. Patients were examined before treatment and every month of the treatment. Assessments were made by investigators according to the Investigator and the Patient Global Improvement Indices (IGII) and (PGII). RESULTS: According to the IGII results, a complete response was observed in 12% of the diclofenac group and 22% of the imiquimod group. For the PGII scores, a complete response was observed in 28% of the diclofenac group and 23% of the imiquimod group. There were no significant differences between the two groups (p > 0.05). Both treatments were well tolerated, with most adverse events related to skin. CONCLUSION: The two drugs were found to be equally effective and safe in the treatment of actinic keratosis but complete remission was very low. Therefore, topical treatments with these two drugs were not seen to be completely effective, and combined therapies and further studies are needed.
AbstractOBJECTIVES: To discover additional diagnostic findings on step sections of biopsy samples showing features of actinic keratosis on the initial section and to correlate such findings with clinical and histological variables. DESIGN: Prospective study comparing initial histological findings with those noted on deeper tissue levels. SETTING: University-based dermatopathology practice. PATIENTS: Fifty-seven patients (36 men and 21 women) with biopsy samples from 69 skin lesions. MAIN OUTCOME MEASURES: Identification of additional pathological diagnoses in step sections and correlation with clinical diagnosis, size and location of lesion, history of skin cancer or immunosuppression, size and handling of specimen, and presence of ulceration on the initial level. RESULTS: Additional diagnostic findings were present on step sections in 23 specimens (33%), including 9 (13%) with squamous cell carcinoma in situ, 3 (4%) with basal cell carcinoma, and 2 (3%) with invasive squamous cell carcinoma. Three variables were significantly correlated with the discovery of cancer on step sections: (1) ulceration on the first level, (2) clinical diagnosis of skin cancer, and (3) history of skin cancer diagnosed by biopsy examination. The latter 2 variables were also correlated with the discovery of any additional finding, whether benign or malignant, on step sections. CONCLUSIONS: In biopsy samples initially diagnostic of actinic keratosis, examination of step sections contributes clinically important information. Step sections are particularly useful when a clinical diagnosis of skin cancer is present. The results of this study confirm the pathogenetic importance of actinic keratosis as a precursor to fully evolved malignant neoplasia and suggest that such lesions merit thorough histological study.
Proliferative Actinic Keratosis: Three Representative Cases
AbstractOBJECTIVE: This article describes a new subtype of actinic keratosis that exhibits proliferative characteristics both histologically and clinically. We describe three representative cases occuring in the presence of infiltrative squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC). METHODS: Histories of each lesion in the three cases discussed were obtained. The lesions were removed by Mohs micrographic surgery. Permanent sections, stained with hematoxylin and eosin, were examined and studied under light microscopy. RESULTS: All three lesions had failed conventional treatment with liquid nitrogen and/or 5-fluorouracil (5-FU). Histologic examination of the lesions revealed sheets of dysplastic cells growing along the basal layer of the epidermis and migrating down hair follicles and sweat ducts. An associated infiltrative SCC and/or BCC was found in each case. CONCLUSIONS: Proliferative actinic keratosis is resistant to standard therapies because of deep migration of abnormal cells along hair follicles and sweat ducts. It has a strong propensity to develop infiltrative SCC and may occur concomitantly with BCC.
Expert Opinion on Drug Delivery · 2018 · 10 citations
Actinic keratosis and imiquimod: a review of novel carriers and patents
AbstractINTRODUCTION: Actinic keratosis is one of the most common disorder characterized by erythematic and generally attached scaly lesions which are present either alone or in clusters. World Health Organization defines actinic keratosis as a common intraepidermal neoplasm of sun-damaged skin, characterized by variable atypia of keratinocytes. AREAS COVERED: At the beginning of the 20th century, a new immunomodulator molecule, imiquimod, appears in the market for the treatment of actinic keratosis but suffers from the pitfalls of the conventional approach of dosage form preparation including high dose, poor stability and more side effects. The present article attempts to compile the scatter information related to actinic keratosis and imiquimod at one place. The special emphasis will be made on the information available in various research articles and patents with respect to the efforts made for overcoming shortcomings associated with imiquimod by novel drug delivery or other approaches. EXPERT OPINION: The conventional drug delivery systems are unsuccessful to improve the actinic keratosis. The patient acceptance and compliance with these treatments are generally poor due to associated side effects, poor cosmetic outcomes and high costs. Therefore, several available and reported novel therapeutic approaches are being developed in order to provide better action.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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