DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for keratoacanthoma — screening already-approved drugs against its 11-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleKeratoacanthoma maps to a 11-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 keratoacanthoma 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
NRAS proto-oncogene, GTPase (NRAS) — NRAS 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ZIO · 1.55 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
Keratoacanthoma is a relatively common tumour of sun-exposed skin in fair-skinned middle-aged and older people. It can be viewed as an aborted squamous cell carcinoma that only rarely progresses to a growing carcinoma. Its rapid evolution passes through proliferative, mature, and involuting stages over weeks. The tumour is likely derived from hair follicle cells; its cause is unclear, though ultraviolet light, viruses, oncogenic chemicals, and epidermal growth factor have been considered. Histologically it can be very difficult to distinguish from cutaneous squamous cell carcinoma, but the overall architecture usually allows separation.
A 1991 study from Brisbane reviewed 111 keratoacanthomas in 106 patients treated by curettage and electrodesiccation. Mean patient age was 64–65 years, sex distribution was nearly equal. Four keratoacanthomas recurred over 3 to 26 months. The authors concluded that curettage and electrodesiccation is an efficient and effective therapy.
A much larger 2016 retrospective study from Stanford examined 363 keratoacanthomas in 261 patients treated with various modalities. Overall resolution after first treatment was 97.2%, with 1.1% recurring and 1.7% persisting. Surgical excision or Mohs surgery gave significantly lower recurrence rates (under 1%) than non-surgical treatments, whose recurrence or persistence rates ranged from 12.5% to 33.3%. For non-surgical first treatments, median time to resolution was 3 months for active surveillance (n=23), 1.4 months for cryotherapy (n=2), 3 months for electrodesiccation and curettage (n=7), and 6 months for medications (topical, intralesional, or oral, n=11). All recurrent or persistent lesions resolved after a second treatment, which was either excision or Mohs surgery. No metastases were found. The authors noted that cryotherapy resolution rate in their small sample was only 67%, lower than a prior expert opinion of 99%, and that non-surgically treated keratoacanthomas can take up to a year to resolve.
A 2018 case report described an 86-year-old patient whose keratoacanthoma was treated with intralesional bleomycin injection combined with electroporation. Electroporation is known to enhance bleomycin cytotoxicity in vivo by 300- to 700-fold. The tumour had completely regressed by day 71. The authors suggested this could be a valid alternative approach, but this is a single case.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Surgical Oncology · 1979 · 80 citations
The keratoacanthoma: A review
AbstractThe keratoacanthoma (KA) is a relatively common tumor which most often occurs on the sun-exposed areas of light skinned individuals of middle age and older. It may be viewed as an aborted squamous cell carcinoma that only in rare instances evolves into a progressively growing squamous cell carcinoma. As such, the recognition of the true nature and the proper management of this tumor is of considerable practical importance. The rapid evolution of a KA may be divided into a proliferative stage, a fully developed tumor, and an involuting stage. Within weeks it develops from a rapidly growing, firm, smooth nodule into a mature bud or dome-shaped tumor with a central keratotic core that finally degenerates into an involuting keratinous mass. Although the KA usually appears as a solitary lesion, multiple tumors may be found, as may a number of morphologic and syndromic variants, including the appearance of the KA in the Torre syndrome. The KA is likely to be derived from cells of the hair follicle. Its etiology is unclear, although ultraviolet light, viruses, oncogenic chemicals, and epidermal growth factor have been considered. The histologic features of the KA are often very similar to those of a cutaneous squamous cell carcinoma; however, the tumor architecture usually provides a basis for their distinction.
Australasian Journal of Dermatology · 1991 · 24 citations
EVALUATION OF CURETTAGE AND ELECTRODESICCATION IN TREATMENT OF KERATOACANTHOMA
AbstractThe reports from all keratoacanthoma curettings which were submitted to a Brisbane pathology practice over a two year period were reviewed. Those followed up for less than 12 months were not included in the analysis, unless recurrence occurred. Of 150 submitted, 111 keratoacanthomas in 106 patients could be studied. The sex distribution was almost equal, and the mean age of patients was 65 years for females and 64 years for males. Four keratoacanthomas recurred over periods ranging from 3 to 26 months. Curettage and electrodesiccation is shown to be an efficient and effective form of therapy.
British Journal of Dermatology · 2016 · 16 citations · open access
An 18-year retrospective study on the outcomes of keratoacanthomas with different treatment modalities at a single academic centre
AbstractDear Editors, The clinical course for keratoacanthomas (KAs) varies from self‐resolving to invasive cancers.1,2 KA is often treated with surgical intervention,2,3 but other treatments such as electrodessication and curettage,4 cryotherapy,4 topical medications,2,5 intralesional chemotherapy,2 acitretin2 and active surveillance6 have been employed. Randomized controlled studies of different treatment modalities are lacking. The largest systematic review consisted of 113 case reports and case series (445 patients included) and reported 18 recurrent or persistent KA cases (4%),2 but this data is prone to publication bias, as unusual cases are more likely to be reported and treatment outcomes could not be directly compared. Our study examines KA recurrence and persistence rates of different treatment approaches at a single institution. After Institutional Review Board approval, we searched the Stanford Cancer Institute Research Database from January 1998 to February 2016 using the keywords ‘keratoacanthoma’, ‘crateriform’ or ‘cup‐shaped’ and applied the following two inclusion criteria: (i) at least one KA‐positive biopsy read by a Stanford dermatopathologist and (ii) at least one dermatology visit documenting treatment of KAs. After manual chart review, 261 patients (with 363 KAs) met these criteria (Fig. 1). ‘Recurrence’ was defined as regrowth of treated lesions documented as no clinically visible lesion after first treatment approach (FTA). ‘Persistence’ was defined as lesions clinically visible at the same anatomic location after FTA. Flowchart of the study. ED&C, electrodessication and curettage; 5‐FU, 5‐fluorouracil; IL, intralesional; Pts, patients. Average age at KA diagnosis was 73 years (SD 11·7). Median follow‐up time was 2·3 years (range 0–17·9). Overall resolution rate of KA was 97·2% (353 of 363 KAs) after the FTA, with 2·8% either recurring [four of 363 KAs (1·1%)] or persisting [six of 363 KAs (1·7%)]. The median size of resolved and recurring/persisting KAs was 1·0 cm (range 0·3–4·5) and 1·1 cm (range 0·4–1·6), respectively. There was no significant difference in age, sex, race and immunosuppression status between individuals with KAs that resolved after the FTA (n = 251 patients) and those whose KAs did not (n = 10 patients). Of the 21 patients who were immunosuppressed, 20 experienced KA resolution after FTA and one did not. Surgical treatment by excision or Mohs surgery led to significantly lower recurrence rates (< 1%) than nonsurgical treatments, whose recurrence or persistence rates ranged from 12·5% to 33·3% (Fig. 1). To assist with patient counselling and estimation of duration needed for monitoring KAs, time to recurrence and duration of persistence after the FTA are shown in Table 1. Median time to recurrence was 3 months (range 1·5–7·5) when all treatment modalities were considered. Median persistence time for persistent KAs prior to initiation of second treatment approach (STA) was 5 months (range 3·8–11·3). All recurrent and persistent KAs resolved after the STA, which was either Mohs surgery (n = 5) or excision (n = 5). No metastatic KA cases were found. Time to recurrence and duration of persistence after the first treatment approach for recurrent and persistent keratoacanthomas (KAs), respectively, at Stanford, compared with our tabulation of Savage et al. systematic review (2013) IL, intralesional. aCalculated from the date of the first procedure (Mohs surgery, excision or electrodessication and curettage) to the date of the recurrence. bCalculated from the date of first treatment initiation to the date of second treatment (which were either Mohs surgery or excision). cThe 2013 systematic review by Savage et al. reported 18 recurrent/persistent cases. However, upon re‐examination of individual cases, we determined that two cases (reported by Calonje et al. and Schwartz et al.) did not meet our definitions of recurrence/persistence and were thus excluded. Median and range are reported where there are more than two KA cases. All recurrent and persistent KAs reported here subsequently underwent excision or Mohs surgery with 100% resolution at follow‐up. Time to recurrence and duration of persistence after the first treatment approach for recurrent and persistent keratoacanthomas (KAs), respectively, at Stanford, compared with our tabulation of Savage et al. systematic review (2013) IL, intralesional. aCalculated from the date of the first procedure (Mohs surgery, excision or electrodessication and curettage) to the date of the recurrence. bCalculated from the date of first treatment initiation to the date of second treatment (which were either Mohs surgery or excision). cThe 2013 systematic review by Savage et al. reported 18 recurrent/persistent cases. However, upon re‐examination of individual cases, we determined that two cases (reported by Calonje et al. and Schwartz et al.) did not meet our definitions of recurrence/persistence and were thus excluded. Median and range are reported where there are more than two KA cases. All recurrent and persistent KAs reported here subsequently underwent excision or Mohs surgery with 100% resolution at follow‐up. Median time to resolution for KAs after nonsurgical FTAs were as follows: active surveillance was 3 months (range 0·6–17, n = 23), cryotherapy was 1·4 months (range 1·2–1·7, n = 2), electrodessication and curettage was 3 months (range 1·7–5·0, n = 7) and medications (topical, intralesional or oral) was 6 months (range 1·6–12·6, n = 11). Our data provides a single‐site source of recurrence and persistence rates of KAs treated with a variety of FTAs (Fig. 1). Although direct comparison of our data with prior systematic reviews is difficult owing to differences in methodology, differences between our data and the largest systematic review2 to date are shown in Table 1. Our median persistence duration of KA after FTA [median 5 months (range 3·8–11·3), n = 6] was different from the median persistence time after FTA in the Savage et al. systematic review [18 months (range 1·5–29·0), n = 3], although the sample size was small. Savage et al. also reported that four of 16 patients required more than two treatments, while none of 261 patients at Stanford required more than two treatments. Compared with a previous study of 43 KAs treated with Mohs surgery,3 KA recurrence after Mohs surgery was threefold lower (2·4% vs. 0·8%). While the number of patients with KA treated with cryotherapy is small, our resolution rate was only 67%, lower than a prior expert opinion of 99%.4 Lastly, KAs treated with nonsurgical approaches including active surveillance can take up to 1 year to resolve. Hence, KAs persisting after 1 year would be candidates for surgical removal, although multicentre studies are needed to establish optimal duration for expectant management. Despite our retrospective study being the largest single‐site study to date, limitations include lack of multivariate analysis owing to low sample size, and nonrandomized nonblinded design. Funding sources: D.C.T. was supported by the Stanford Medical Scholars Research Program. Stanford Cancer Research Database was supported in part by National Cancer Institute Cancer Center Support Grant 5P30CA124435 and Stanford National Institutes of Health/National Center for Research Resources Clinical and Translational Science Awards award number UL1 RR025744. Conflicts of interest: A.L.S.C. is a clinical investigator for studies sponsored by Merck, Genentech and Novartis. No funding/sponsor was involved in study design, data collection, analysis and interpretation, and writing of the manuscript. The study was approved by the Stanford Institution Review Board.
Dermatology and Therapy · 2018 · 9 citations · open access
Successful Treatment of a Keratoacanthoma with Electrochemotherapy: A Case Report
AbstractINTRODUCTION: Few studies have evaluated the efficacy of intralesional bleomycin injection combined with electroporation for the treatment of cutaneous tumors. However, the phenomenon that electroporation can enhance the cytotoxicity of bleomycin in vivo by 300-700 fold has been intensely investigated. CASE PRESENTATION: Keratoacanthoma in an 86-year-old patient was treated with intralesional bleomycin combined with electroporation. Treatment consisted of local application of shorty and intense electric pulses followed by local injection of bleomycin. Electroporation was always well tolerated by the patient, with no significant complaints, and the tumor had completely regressed by day 71 of the follow-up. CONCLUSION: The results suggest that intralesional bleomycin injection combined with electroporation could represent a valid alternative therapeutic approach for the treatment of keratoacanthomas.
JAAD Case Reports · 2018 · 4 citations · open access
Multiple reactive keratoacanthomas treated with zinc oxide wraps and intralesional corticosteroids
AbstractKeratoacanthoma (KA), a neoplasm of epidermal cells from the hair follicle unit,1 is often present on chronic sun-exposed skin.2 Many facets of this neoplasm are controversial, including its epidemiology, etiology, and biologic behavior, including malignant potential and recommendations for treatment.2 This case presents a treatment option for multiple reactive KAs that is both conservative and noninvasive.
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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