DeCure for Grade III Prostatic Intraepithelial Neoplasia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Grade III Prostatic Intraepithelial Neoplasia — screening already-approved drugs against its 12-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGrade III Prostatic Intraepithelial Neoplasia maps to a 12-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 grade iii prostatic intraepithelial neoplasia 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
HRas proto-oncogene, GTPase (HRAS) — HRAS 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ELT · 1.66 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
In a 2002 study of 31 men who had a follow-up biopsy three years after a diagnosis of high grade prostatic intraepithelial neoplasia (HGPIN), 25.8% were found to have prostate cancer, 35.5% had HGPIN only, and 38.7% had no disease. The mean serum PSA rose from 6.88 to 9.69 ng/dl over the interval, but change in PSA was not associated with cancer detection on univariate analysis. All four men who underwent radical prostatectomy had organ-confined disease. The authors concluded that a repeat biopsy at a delayed interval is recommended regardless of PSA changes.
A 1996 study of 93 patients with PIN found subsequent carcinoma on repeat biopsy in 13.3% of those with low grade PIN and 47.9% of those with high grade PIN. In the high grade group, digital rectal examination, serum PSA, and transrectal ultrasound appearance were statistically different between men with and without subsequent cancer on univariate analysis; on multivariate analysis only digital rectal examination and PSA were predictive. The authors stated that high grade PIN is a strong predictor of subsequent cancer, especially in men with abnormal digital rectal examination and elevated PSA.
A 2000 study examined 45 men with isolated HGPIN who underwent repeat biopsy within one year using various strategies: targeting only the neoplasia site, sextant biopsy, sextant plus bilateral transition zone, or an 11-core multisite approach. Cancer was found in 22% of the men. Of 15 cores positive for cancer, 8 were at the original HGPIN site, 6 at a random sextant site, and 1 in the transition zone. The authors concluded that the optimal repeat biopsy strategy had not been determined but should at minimum include targeting the area of known HGPIN and the ipsilateral sextants.
A 2001 review of genetic alterations in PIN noted that PIN is the histologic lesion most strongly associated with prostate cancer and is postulated to be a premalignant lesion, but stated that much of its natural history remains unknown. The review called for a more fundamental understanding of the relationship between PIN and invasive tumours at the molecular level. What is still missing is a prospective trial that stratifies patients by molecular markers or genetic alterations, rather than by histology and PSA alone, and that tests whether any intervention alters the progression rate. The natural history data remain limited to small, single-centre cohorts, and no randomised trial has established a standard for surveillance intervals or biopsy protocols.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Urology · 2002 · 107 citations
Followup Interval Prostate Biopsy 3 Years After Diagnosis of High Grade Prostatic Intraepithelial Neoplasia is Associated With High Likelihood of Prostate Cancer, Independent of Change in Prostate Specific Antigen Levels
AbstractPURPOSE: Repeat biopsy has been advocated following the diagnosis of high grade prostatic intraepithelial neoplasia to exclude coexisting prostate cancer. We further define the natural history of high grade prostatic intraepithelial neoplasia by determining the incidence of prostate cancer 3 years following diagnosis. MATERIALS AND METHODS: A total of 31 men underwent followup interval biopsy 3 years after high grade prostatic intraepithelial neoplasia diagnosis in 1996 to 1997, regardless of change in serum prostate specific antigen (PSA) or digital rectal examination findings. A single pathologist reviewed all biopsy specimens. All men had a minimum of 12 biopsy cores taken at the time of diagnosis. RESULTS: A 3-year followup interval biopsy eight (25.8%) men had prostate cancer, 11 (35.5%) had high grade prostatic intraepithelial neoplasia only and 12 (38.7%) had no disease. Mean serum PSA at diagnosis and before the followup biopsy was 6.88 and 9.69 ng./dl., respectively (p = 0.008). Of the men 48% had less than a 1.0 unit increase in serum PSA. Upon univariate regression analysis change in serum PSA was not associated with the detection of prostate cancer (p >0.10). All 4 patients who subsequently underwent radical prostatectomy had organ confined disease. CONCLUSIONS: In a high proportion of men with high grade prostatic intraepithelial neoplasia prostate cancer will develop in a 3-year interval. Our findings support the concept that high grade prostatic intraepithelial neoplasia is a precursor to prostate cancer and that repeat biopsy at a delayed interval is recommended regardless of changes in PSA.
Prostatic Intraepithelial Neoplasia: Influence of Clinical and Pathological Data on the Detection of Prostate Cancer
AbstractPURPOSE: We attempted to characterize patients diagnosed with prostatic intraepithelial neoplasia without concurrent cancer on biopsy who had prostate cancer on subsequent biopsy. MATERIALS AND METHODS: The records of 93 patients with low and high grade prostatic intraepithelial neoplasia without concurrent cancer on initial biopsy were analyzed. The relationships among prostatic intraepithelial neoplasia grades, patient age, digital rectal examination, serum prostate specific antigen (PSA), transrectal ultrasound appearance and final pathological results were investigated. RESULTS: Subsequent carcinoma was found on repeat biopsy in 13.3% of patients with low grade and 47.9% with high grade prostatic intraepithelial neoplasia (p < 0.001). In the former group digital rectal examination, patient age, serum PSA and transrectal ultrasound were not predictive of cancer. Transrectal ultrasound appearance, digital rectal examination and serum PSA were statistically different between high grade prostatic intraepithelial neoplasia with and without subsequent cancer (p < 0.001, p = 0.008 and p = 0.016, respectively, univariate analysis). On multivariate analysis of patients with high grade prostatic intraepithelial neoplasia only digital rectal examination and PSA were predictive of subsequent carcinoma. CONCLUSIONS: High grade prostatic intraepithelial neoplasia is a strong predictor of subsequent cancer, especially in men with abnormal digital rectal examination and elevated serum PSA. Patients with high grade prostatic intraepithelial neoplasia should undergo repeat biopsy to exclude cancer. Further investigations are needed to optimize the treatment of patients with low grade prostatic intraepithelial neoplasia.
STRATEGY FOR REPEAT BIOPSY IN PATIENTS WITH HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA
AbstractPURPOSE: The finding of high grade prostatic intraepithelial neoplasia in a biopsy specimen without prostate cancer warrants repeat biopsy because of the risk of concurrent cancer. However, to our knowledge the optimal repeat biopsy technique has not yet been defined. We determined the optimal subsequent biopsy strategy for detecting concurrent cancer in patients diagnosed with high grade prostatic intraepithelial neoplasia. MATERIALS AND METHODS: Of 63 men with isolated high grade prostatic intraepithelial neoplasia on initial biopsy 45 underwent repeat biopsy within 1 year. Certain biopsy patterns were used for repeat biopsy, including only the neoplasia site in 8 men, sextant in 12, sextant plus bilateral transition zone in 13 and 11 core multisite directed (sextant, bilateral transition zone, bilateral anterior horn of the peripheral zone and midline peripheral zone) in 12. We compared the location of high grade disease on the initial biopsy with the cancer site on repeat biopsy. RESULTS: Repeat biopsy revealed cancer in 10 of the 45 men (22%), and the sites of high grade prostatic intraepithelial neoplasia and cancer correlated in 6. Cancer was detected at the sextant locations in 9 men. Of the 15 cores positive for cancer 8 were at the original high grade neoplasia site, 6 at a random sextant biopsy site and 1 in the transition zone. High grade disease was discovered bilaterally in 1 man, while prostatic intraepithelial neoplasia and cancer were detected on the same side in the remaining 9. CONCLUSIONS: The optimal repeat biopsy strategy for patients with high grade prostatic intraepithelial neoplasia has not yet been determined but at a minimum it should include targeting the area of known high grade disease and the ipsilateral sextants.
Prostate Cancer · 2001 · 1 citations · open access
Genetic Alterations in Prostatic Intraepithelial Neoplasia (PIN)
AbstractProstatic intraepithelial neoplasia (PIN) is the histologic lesion most strongly associated with prostate cancer, and has been postulated to be a premalignant lesion. However, much of the natural history of PIN remains unknown. A more fundamental understanding of the relationship between PIN and invasive tumors at the molecular level is critically needed, and represents an important future challenge for investigators. This chapter reviews the clinical, pathologic, and genetic studies addressing the relationship between PIN and cancer. The final section presents newly developing techniques and research approaches in molecular pathology and describes how these methods can be used to study PIN.
Journal of Case Reports · 2014 · 0 citations · open access
Clear Cell Cribriform Hyperplasia of the Prostate: a Potential Diagnostic Pitfall
AbstractCribriform lesions of the prostate can be of difficult histological interpretation and have diagnostic pitfalls. We discuss the case of a patient presenting with urinary obstruction symptoms for which he underwent transurethral prostatic resection. Histology of the prostate chips revealed a cribriform lesion which posed a challenging differential diagnosis between benign hyperplastic lesion, prostatic intraepithelial neoplasia and possibly a malignant lesion. The careful examination of the cytology of the lesion, the use of immunohistochemistry and peer review of the case helped excluding cribriform prostatic carcinoma and cribriform intraepithelial neoplasia. We diagnosed this case as clear cell cribriform hyperplasia, an uncommon variant of benign prostatic hyperplasia which does not carry any malignant potential. Awareness about this entity is essential to avoid misdiagnosis which can potentially lead to a wrong clinical management.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
