DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for prostate neuroendocrine neoplasm — screening already-approved drugs against its 25-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleProstate neuroendocrine neoplasm maps to a 25-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 prostate neuroendocrine neoplasm 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
fibroblast growth factor receptor 4 (FGFR4) — FGFR4 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 1~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8KH8 · 1.49 Å · ligand 1-[4-[(1~{R})-1-[3,5-bis(chloranyl)pyridin-4-yl]ethoxy]-5-cyano-pyridin-2-yl]-3-[6-methanoyl-5-[(4-methyl-2-oxidanylidene-piperazin-1-yl)methyl]-3-(2-morpholin-4-ylethoxy)pyridin-2-yl]urea (VVW). Experimental structure, not a prediction.
What the evidence adds up to
Neuroendocrine prostate cancer is a rare subtype, accounting for roughly 1–5% of all prostate cancers, and carries a poor prognosis. In advanced prostate cancer, focal neuroendocrine trans-differentiation of adenocarcinoma occurs in about 30% of cases, and androgen deprivation therapy is increasingly recognised as a key driver of this phenomenon. Two case reports from 2003 describe patients whose tumours progressed universally with neuroendocrine differentiation during androgen suppression therapy, with the authors noting that no successful therapy existed at that time. A 2023 Russian review states that in 15–20% of prostate cancer patients receiving hormone therapy, signs of neuroendocrine differentiation may develop, typically 18–36 months after treatment begins, and that specific diagnostic and treatment algorithms have not been developed.
A 2024 case report describes a 74-year-old man diagnosed with neuroendocrine carcinoma of the prostate who was treated with etoposide and cisplatin (EP therapy) and remained in remission one year later. The authors note that such carcinomas are rare and have poor prognoses, and that information regarding treatments that can improve prognosis is needed. Another 2024 case report details a 63-year-old patient with mixed prostate cancer including a large cell neuroendocrine component at a localised stage, but does not report treatment outcome or survival data.
Two review articles from 2019 and 2022 discuss the role of the tumour microenvironment in mediating neuroendocrine differentiation and emphasise that additional research is required to develop effective treatment strategies. The 2022 review mentions that several potential therapeutic approaches, including combination immunotherapies, have been uncovered, but that further work is needed to exploit tumour cell and microenvironment heterogeneity. The 2019 review states that understanding the tumour microenvironment could reveal potential therapeutic targets against this aggressive form of prostate cancer.
What is still missing are large, prospective clinical trials with sufficient patient numbers to establish standard treatment algorithms. The rarity of the disease makes trial design difficult, and no validated biomarkers exist to stratify patients or predict response to specific therapies. Funding for multi-centre collaborative studies and for the development of diagnostic tools to distinguish neuroendocrine from adenocarcinoma components in mixed tumours remains inadequate.
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 Prostate · 1999 · 375 citations · open access
Neuroendocrine differentiation in prostatic carcinoma
AbstractBACKGROUND: Information is presented on prostatic neuroendocrine cells and neuroendocrine differentiation in prostatic carcinoma. The prognostic and therapeutic implications of neuroendocrine differentiation in prostatic carcinoma are reviewed. METHODS: Data are presented that support the intriguing link between neuroendocrine differentiation, tumor progression, and androgen-independent prostate cancer. The hormones, and the receptors, expressed by prostatic neuroendocrine cells are investigated in order to elucidate their significance for prognosis and therapy. RESULTS: The prognostic significance of neuroendocrine differentiation in prostatic malignancy has been controversial, but recent studies employing markers such as chromogranin A and neuron-specific enolase suggest that neuroendocrine differentiation, as reflected by increased tissue expression and/or blood levels of these neuroendocrine secretory products, correlates with poor prognosis, tumor progression, and androgen-independence. Since all malignant neuroendocrine cells are devoid of androgen receptors and since neuroendocrine phenotypic expression is not suppressed by androgen ablation, clonal propagation of androgen receptor-negative neuroendocrine cells may play an important role in the pathway towards the androgen-independent state of prostatic carcinoma. This would have significant implications for the treatment of prostate cancer, as several of the hormones known to be expressed by neuroendocrine-differentiated, malignant prostatic cells are potential candidates for drug therapy. A limited number of hormones have been tested in this context, in particular somatostatin, bombesin, and serotonin. CONCLUSIONS: Neuroendocrine differentiation in carcinoma of the prostate appears to be associated with poor prognosis, tumor progression, and the androgen-independent state, for which there is currently no successful therapy. Therefore, new therapeutic protocols and trials need to be developed to test drugs based on neuroendocrine hormones and/or their antagonists. An evaluation of this new therapeutic approach against prostatic carcinoma with neuroendocrine differentiation, including hormone-refractory cancer, is easily justified, since these tumors are unresponsive to current modes of therapy.
Neuroendocrine Differentiation of Prostate Cancer—An Intriguing Example of Tumor Evolution at Play
AbstractOur understanding of neuroendocrine prostate cancer (NEPC) has assumed a new perspective in light of the recent advances in research. Although classical NEPC is rarely seen in the clinic, focal neuroendocrine trans-differentiation of prostate adenocarcinoma occurs in about 30% of advanced prostate cancer (PCa) cases, and represents a therapeutic challenge. Even though our knowledge of the mechanisms that mediate neuroendocrine differentiation (NED) is still evolving, the role of androgen deprivation therapy (ADT) as a key driver of this phenomenon is increasingly becoming evident. In this review, we discuss the molecular, cellular, and therapeutic mediators of NED, and emphasize the role of the tumor microenvironment (TME) in orchestrating the phenotype. Understanding the role of the TME in mediating NED could provide us with valuable insights into the plasticity associated with the phenotype, and reveal potential therapeutic targets against this aggressive form of PCa.
The Prognostic Value of Neuroendocrine Differentiation in Adenocarcinoma of the Prostate in Relation to Progression of Disease After Endocrine Therapy
AbstractPURPOSE: We evaluated the prognostic impact of neuroendocrine differentiation in prostate cancer with regard to the onset of endocrine therapy failure. MATERIALS AND METHODS: A retrospective study was performed on 72 transurethral resection specimens from patients who subsequently underwent endocrine therapy for prostate cancer and were followed for 44 to 95 months. Progression-free interval was recorded. Distribution pattern and proportion of neuroendocrine cells were examined in transurethral resection specimens. Neuroendocrine cells were identified based on immunoreactivity for chromogranin A. RESULTS: Of 32 patients with progressive disease 27 died of prostate cancer. Chromogranin A positive cells were found in 40 of the 72 prostate cancers (55%). In a Cox proportional hazards analysis neuroendocrine differentiation of the tumor showed a negative correlation with progression-free survival (p = 0.022), which proved to be independent of the Gleason score (p < 0.001). CONCLUSIONS: Our results support the view that neuroendocrine differentiation in prostatic adenocarcinomas is a prognostic factor for progressive disease under subsequent endocrine therapy. This prognosticator acts independently of tumor grade.
AbstractNeuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that typically has a high metastatic potential and poor prognosis in comparison to the adenocarcinoma subtype. Although it can arise de novo, NEPC much more commonly occurs as a mechanism of treatment resistance during therapy for conventional prostatic adenocarcinoma, the latter is also termed as castration-resistant prostate cancer (CRPC). The incidence of NEPC increases after hormonal therapy and they represent a challenge, both in the radiological and pathological diagnosis, as well as in the clinical management. This article provides a comprehensive imaging review of prostatic neuroendocrine tumors.
Journal of Endocrinology · 2022 · 10 citations · open access
Heterogeneity and the tumor microenvironment in neuroendocrine prostate cancer
AbstractNeuroendocrine prostate cancer, generally arising late in the disease trajectory, is a heterogeneous subtype that infers a worse prognosis and limited treatment options for patients. Characterization of the complex landscape of this disease subtype and scrutiny of the relationship between tumor cells and cells of the surrounding tumor microenvironment have aided in elucidating some of the mechanisms of neuroendocrine disease biology and have uncovered a multitude of signaling pathways involved in disease transdifferentiation under therapeutic selection. In this review, we discuss current efforts to better understand the heterogeneous landscape of neuroendocrine prostate cancer and summarize research efforts to define the interplay between tumor cells and the microenvironment, with an emphasis on the immune component. Research efforts have uncovered several potential therapeutic approaches that may improve disease outcomes for patients diagnosed with neuroendocrine prostate cancer, including the potential for combination immunotherapies. However, additional research is required to fully address and exploit the contribution of tumor cell and microenvironment heterogeneity in developing effective treatment strategies.
The Japanese Journal of Urology · 2003 · 1 citations · open access
NEUROENDOCRINE DIFFERENTIATION IN ADENOCARCINOMA OF THE PROSTATE WITH PROGRESSION OF DISEASE DURING HORMONAL TREATMENT; A REPORT OF TWO CASES
AbstractProstatic neuroendocrine (NE) carcinoma is a rare situation and the NE differentiation in the prostate adenocarcinoma appears to be characterized as poor prognosis, rapid tumor progression and the androgen-independent state, for which there is currently no successful therapy. We report two cases of NE differentiated prostatic carcinoma, which were diagnosed adenocarcinoma initially and the tumors progressed universally with NE differentiation during androgen suppression therapy.
IJU Case Reports · 2024 · 1 citations · open access
Prostate neuroendocrine carcinoma successfully treated with etoposide and cisplatin
AbstractIntroduction: The frequency of neuroendocrine carcinoma of the prostate is low, accounting for approximately 1%-5% of all prostate cancers. Herein, we report the case of a patient who was diagnosed with prostate neuroendocrine carcinoma and successfully treated with etoposide and cisplatin. Case presentation: A 74-year-old man presented to the urology department with the chief complaint of urinary retention. After a thorough examination, he was diagnosed with neuroendocrine carcinoma of the prostate and treated with etoposide and cisplatin, called "EP therapy." The patient remained in remission 1 year later. Conclusion: A patient with neuroendocrine carcinoma of the prostate was successfully treated with etoposide and cisplatin, and the patient remained in remission. Prostate neuroendocrine carcinomas are rare and have poor prognoses. Therefore, information regarding treatments that can improve prognosis is needed.
AbstractIn Russia, prostate cancer is a common disease with fast increasing incidence. In the vast majority of prostate cancer patients receiving hormone therapy, on average 18–36 months after the start of treatment refractoriness to androgen ablation develops. In 15–20 % of patients, signs of neuroendocrine differentiation may develop.Neuroendocrine prostate cancer is an aggressive variant of castration-resistant prostate cancer with poor prognosis and low survival.Due to the rarity of these types of tumors, specific diagnostic and treatment algorithms have not been developed. As a rule, they are similar to the methods for other malignant forms of prostate cancer and neuroendocrine tumors.
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.
