DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Prostate Small Cell Carcinoma — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleProstate Small Cell Carcinoma maps to a 45-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 small cell carcinoma 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
Bruton tyrosine kinase (BTK) — BTK 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 7h-pyrrolo[2,3-d]pyrimidin-4-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6VXQ · 1.4 Å · ligand N-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl}benzamide (RQS). Experimental structure, not a prediction.
What the evidence adds up to
A 2009 molecular analysis of a single case found that concurrent small cell neuroendocrine carcinoma and acinar adenocarcinoma of the prostate shared a TP53 gene mutation, suggesting a common clonal origin. Transcriptome profiling of that case identified 99 genes with greater than ten-fold differential expression between the two components; the small cell component showed upregulation of proliferative and neuroendocrine markers and tyrosine kinase receptors, and downregulation of cell adhesion molecules. A 2019 study using patient-derived xenograft lines detected expression of stem cell transcription factors LIN28A, NANOG, POU5F1, and SOX2 in small cell carcinoma lines LuCaP 93, 145.1, and 145.2, and in non-adenocarcinoma lines LuCaP 173.1 and 173.2A. Transfection of those factors from LuCaP 145.1 into non-small cell prostate carcinoma cells and fibroblasts altered gene expression and produced stem-like colonies, with a ten-fold lower expression of B2M in the transfected cells, matching the low B2M characteristic of LuCaP 145.1.
A 2011 review states that a little less than half of small cell carcinoma cases are associated with conventional high-grade acinar adenocarcinoma, and that the majority of patients present with advanced disease and disproportionately low PSA levels compared to patients with conventional adenocarcinoma. Treatment, according to that review, consists mainly of chemotherapy associated with surgery, with radiation reserved for selected cases. A 2018 case report reiterates that small cell prostate carcinoma lacks PSA secretion, does not respond to androgen suppression therapy, and presents with osteolytic bone lesions and visceral metastasis.
A 2024 review discusses transcription factors including the ETS family, NF-κB, AP-1, MYC, and the androgen receptor in prostate cancer generally, and mentions therapeutic interventions targeting transcription factor pathways such as small molecule inhibitors, gene therapies, and immunotherapies, but does not report any clinical trial results for small cell carcinoma specifically. A 1990 overview notes that reliable study results in prostate cancer are scarce because treated tumors represent a wide variety of natural history and therapeutic response, and that better treatment selection depends on ongoing randomised trials, new drugs, and basic studies on growth potential and invasiveness.
What is still missing are prospective clinical trials enrolling exclusively small cell carcinoma of the prostate, which remains a rare diagnosis. No randomised data exist to define a standard chemotherapy regimen, and no targeted therapy has been tested in a dedicated trial for this subtype. Patient stratification by molecular markers such as TP53 status or stem cell transcription factor expression has not been incorporated into treatment decisions. Funding for multi-centre collaboration and for the development of patient-derived models that recapitulate the de-differentiation pathway is lacking.
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 · 2009 · 78 citations
Shared <i>TP53</i> gene mutation in morphologically and phenotypically distinct concurrent primary small cell neuroendocrine carcinoma and adenocarcinoma of the prostate
AbstractBACKGROUND: Small cell carcinoma of the prostate is an uncommon neoplasm, the origin of which has been controversial. To address this, we performed transcriptome profiling and TP53 sequencing of concurrent small cell and prostatic adenocarcinoma to determine the relationship between these entities. METHODS: We identified an unusual case of primary prostate cancer that contained adjacent acinar adenocarcinoma (Gleason score 4 + 3 = 7) and small cell carcinoma. We performed laser capture microdissection to isolate tumor components and performed gene expression and TP53 gene sequence analysis on each component, with results validated by immunohistochemistry for PSA, PSAP, PSMA, androgen receptor, NKX 3.1 and neuroendocrine markers. RESULTS: Transcriptome profiling of the carcinoma components identified 99 genes with a greater than 10-fold differential expression between prostatic adenocarcinoma and small cell carcinoma, many of which have not been previously reported in prostate cancer. The small cell carcinoma component demonstrated upregulation of proliferative and neuroendocrine markers and tyrosine kinase receptors, and downregulation of cell adhesion molecules, supporting the aggressive nature of this form of carcinoma. Sequencing of the TP53 gene suggested a common clonal origin for both components. CONCLUSIONS: This is the first report of a primary small cell carcinoma of the prostate subjected to extensive molecular analysis and the first to show a clonal relation between two morphologically distinct prostate cancer types. The evidence of progression to small cell carcinoma may yield important insights into the pathogenesis of this entity and provide a novel spectrum of molecular markers to further dissect cellular pathways important in tumor progression.
Prostate Cancer · 2011 · 41 citations · open access
Review of Small Cell Carcinomas of the Prostate
AbstractSmall cell carcinoma of the prostate is a rare neoplasm, with only a few series hitherto reported. A little less than half of the cases are associated with conventional acinar adenocarcinoma, which are usually high grade. Although consensus has not been reached, the majority of patients with small cell neuroendocrine carcinoma of the prostate have advanced disease at diagnosis and disproportionally low PSA levels compared to patients with conventional acinar adenocarcinoma. Treatment consists mainly of chemotherapy associated with surgery. Radiation therapy is reserved for selected cases. This study reviews the most up-to-date information on small cell carcinomas of the prostate.
Acta Oncologica · 1990 · 18 citations · open access
Prostatic Cancer: An overview
AbstractReliable study results are scarce in prostate cancer for several reasons. The treated tumors represent a wide variety of natural history and therapeutic response. One assumes to select 'soft' or minimally toxic treatment for patients with good prognostic factors while aggressive treatment is reserved for infaust prognosis. Stage, grade and prognostic factors may influence the indication and choice of treatment. Better treatment selection will depend on the outcome of actual ongoing randomized trials, the development of new drugs or existing drugs in new indications and, above all, basic studies on the growth potential and invasiveness of the prostate cancer cell. Defining the correct treatment for the right cancer in the right patient is our clinical challenge for the next decade.
Transcription Factors in Prostate Cancer: Insights for Disease Development and Diagnostic and Therapeutic Approaches
AbstractTranscription factors (TFs) are proteins essential for the regulation of gene expression, and they regulate the genes involved in different cellular processes, such as proliferation, differentiation, survival, and apoptosis. Although their expression is essential in normal physiological conditions, abnormal regulation of TFs plays critical role in several diseases, including cancer. In prostate cancer, the most common malignancy in men, TFs are known to play crucial roles in the initiation, progression, and resistance to therapy of the disease. Understanding the interplay between these TFs and their downstream targets provides insights into the molecular basis of prostate cancer pathogenesis. In this review, we discuss the involvement of key TFs, including the E26 Transformation-Specific (ETS) Family (ERG and SPDEF), NF-κB, Activating Protein-1 (AP-1), MYC, and androgen receptor (AR), in prostate cancer while focusing on the molecular mechanisms involved in prostate cancer development. We also discuss emerging diagnostic strategies, early detection, and risk stratification using TFs. Furthermore, we explore the development of therapeutic interventions targeting TF pathways, including the use of small molecule inhibitors, gene therapies, and immunotherapies, aimed at disrupting oncogenic TF signaling and improving patient outcomes. Understanding the complex regulation of TFs in prostate cancer provides valuable insights into disease biology, which ultimately may lead to advancing precision approaches for patients.
Bulletin of Urooncology · 2018 · 0 citations · open access
A Rare Tumor: Small Cell Prostate Carcinoma Case Report
AbstractProstate small cell carcinoma is a rare and aggressive tumor. They can be distinguished from classic prostate adenocarcinoma by features such as lack of prostate-specific antigen secretion, failure to respond to androgen suppression therapy, osteolytic bone lesions, and visceral metastasis. Herein, we present a case of previously diagnosed prostate adenocarcinoma that transformed to prostate small cell carcinoma, together with a discussion of the current literature.
Lineage relationship between prostate adenocarcinoma and small cell carcinoma
AbstractAbstract Background Prostate cancer displays different morphologies which, in turn, affect patient outcome. This fact prompted questions about the lineage relationship between differentiated, more treatable prostate adenocarcinoma and poorly differentiated, less treatable non-adenocarcinoma including small cell carcinoma, and the molecular mechanism underlying prostate cancer differentiation. Methods Newly available non-adenocarcinoma/small cell carcinoma PDX LuCaP lines were analyzed for expression of stem cell transcription factors (scTF) LIN28A, NANOG, POU5F1, SOX2, which are responsible for reprogramming or de-differentiation. cDNA of these genes were cloned from small cell carcinoma LuCaP 145.1 into expression vectors to determine if they could function in reprogramming. Results Expression of scTF was detected in small cell carcinoma LuCaP 93, 145.1, 145.2, and non-adenocarcinoma LuCaP 173.1, 173.2A. Transfection of scTF from LuCaP 145.1 altered the gene expression of prostate non-small cell carcinoma cells, as well as fibroblasts. The resultant cells grew in stem-like colonies. Of note was a 10-fold lower expression of B2M in the transfected cells. Low B2M was also characteristic of LuCaP 145.1. Conversely, B2M was increased when stem cells were induced to differentiate. Conclusions This work suggested a pathway in the emergence of non-adenocarcinoma/small cell carcinoma from adenocarcinoma through activation of scTF genes that produced cancer de-differentiation.
Chinese Journal of Cancer Research · 2010 · 0 citations
Small-cell carcinoma of prostate: A case report and literature review
AbstractOne case of small-cell carcinoma (SCC) of prostate was identified at Shangyu people’s hospital. This 70-year-old male had a prior diagnosis of prostatic adenocarcinoma when he was first admitted to the hospital and received anti-androgen treatment. 9 months later, he was readmitted to the hospital and was diagnosed as SCC through biopsy. The article was written to evaluate the clinical and pathological characteristics and treatment of SCC of prostate.
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.
