DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for prostate cancer — 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 moduleProstate cancer 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
approvedDocetaxelApproved drugapprovedCabazitaxelApproved drug
Structures already discussed alongside prostate cancer in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
TUBULIN ALPHA-BETA DIMER, ELECTRON DIFFRACTION — Docetaxel has a real, experimentally solved structure in complex with this target (PDB 1TUB, 3.7 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet txldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1TUB · 3.7 Å · ligand Docetaxel (TXL). Experimental structure, not a prediction.
What the evidence adds up to
In 2005, more than 25% of US surgeons who performed radical prostatectomy did only one such procedure that year, and roughly 80% performed fewer than ten. The authors of that study concluded that this pattern likely leads to poorer outcomes, because a surgeon needs at least 250 procedures to reach the learning curve plateau for cancer control. A 2019 UK-wide survey of 35,823 men who had been treated for prostate cancer 18–42 months earlier found that quality of survival varied by region. After adjusting for treatment and clinical and sociodemographic factors, men in Scotland, Wales, and Northern Ireland reported worse urinary, bowel, sexual, and vitality outcomes than the UK average; within England, South Yorkshire and North-East and Cumbria had poorer self-assessed health. The authors noted that clinically relevant differences were seen for bowel problems and vitality.
Between 2009 and 2012, more drugs were approved by the US Food and Drug Administration for castration-resistant prostate cancer than in the previous three decades, a shift the 2012 review attributes partly to redefined trial designs and endpoints. By 2016, however, a review of sequential use of these new drugs stated that the efficacy of giving them one after another in everyday practice was not supported by clinical trial data, and that evidence of possible cross-resistance had reinforced debate about the best sequence. A 2021 cost analysis from Japan followed 81 men who received androgen deprivation therapy; 56 had metastatic or high-PSA disease, 30 of those developed castration-resistant prostate cancer after a median of 10 months, and 25 received CRPC drugs for a median of 20 months. Over a median follow-up of 48 months, 15 men died of prostate cancer. The median annual drug cost for castration-sensitive disease was 234,000 yen (about 2,187 US dollars), while for CRPC it was 2,041,000 yen (about 19,075 US dollars). The authors concluded that advanced prostate cancer tended to progress rapidly to CRPC, requiring expensive sequential drugs, and that early diagnosis would reduce the economic burden.
A 2024 review notes that while the therapeutic landscape for prostate cancer has expanded to include multiple androgen receptor pathway inhibitors and chemotherapy, controversies remain about managing biochemical recurrence after radical local therapy and about neoadjuvant treatment before it. What is still missing are prospective trial data that confirm the optimal sequencing of drugs for castration-resistant disease, a clear understanding of how regional variations in follow-up care drive differences in quality of survival, and strategies to ensure that surgeons performing radical prostatectomy have sufficient caseloads to reach the learning curve.
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 · 2009 · 66 citations · open access
Low Annual Caseloads of United States Surgeons Conducting Radical Prostatectomy
AbstractPURPOSE: It has been clearly demonstrated that surgeons with increased yearly caseloads have lower complication rates. Moreover it has been shown that a surgeon needs to conduct at least 250 radical prostatectomies to maximize cancer control (the surgical learning curve). MATERIALS AND METHODS: To determine typical annual radical prostatectomy caseloads of surgeons in the United States we analyzed data from 2 independent data sets for 2005, that of a nationally representative sample (Nationwide Inpatient Sample) and a complete record of all hospital discharges from New York State (Statewide Planning and Research Cooperative System). RESULTS: More than 25% of United States surgeons conducting radical prostatectomy in 2005 performed only a single procedure. Approximately 80% of surgeons performed fewer than 10 procedures per year and, thus, are unlikely to reach the plateau of the learning curve during their surgical career. CONCLUSIONS: The current pattern of surgical treatment for prostate cancer leads to many patients being treated by surgeons with low annual caseloads, with likely poorer outcomes as a result.
CA A Cancer Journal for Clinicians · 2012 · 46 citations · open access
Clinical development of novel therapeutics for castration‐resistant prostate cancer
AbstractThere have been more drugs approved by the US Food and Drug Administration for the treatment of castration-resistant prostate cancer in the past 3 years than in the prior 3 decades, with additional drugs on the verge of approval based on the results of recently reported randomized trials. While an improvement in the understanding of the pathogenesis of castration-resistant prostate cancer has undeniably accelerated the transition of novel approaches from "bench to bedside," the recent successes in the treatment of prostate cancer are also a result of the efforts of clinical investigators to redefine the framework in which drugs for castration-resistant disease are evaluated. This review will explore the shifting paradigm in drug development for castration-resistant prostate cancer over the past several decades, and highlight how new definitions, trial designs, and endpoints have facilitated the emergence of new therapies for this challenging disease.
European Urology · 2019 · 8 citations · open access
Regional Variations in Quality of Survival Among Men with Prostate Cancer Across the United Kingdom
AbstractBACKGROUND: Prostate cancer incidence, treatment, and survival rates vary throughout the UK, but little is known about regional differences in quality of survival. OBJECTIVE: To investigate variations in patient-reported outcomes between UK countries and English Cancer Alliances. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional postal survey of prostate cancer survivors diagnosed 18-42mo previously. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Urinary, bowel, and sexual problems and vitality were patient reported using the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. General health was also self-assessed. Regional variations were identified using multivariable log-linear regression. RESULTS AND LIMITATIONS: A total of 35823 men responded, 60.8% of those invited. Self-assessed health was significantly lower than the UK average in Wales and Scotland. Respondents reported more urinary incontinence in Scotland, more urinary irritation/obstruction in Scotland and Northern Ireland (NI), poorer bowel function in Scotland and NI, worse sexual function in Scotland, and reduced vitality/hormonal function in Scotland, Wales, and NI. Self-assessed health was poorer than the English average in South Yorkshire and North-East and Cumbria, with more urinary incontinence in North-East and Cumbria and Peninsula, greater sexual problems in West Midlands, and poorer vitality in North-East and Cumbria and West Midlands. Limitations include difficulty identifying clinically significant differences and limited information on pretreatment conditions. CONCLUSIONS: Despite adjustment for treatment, and clinical and sociodemographic factors, quality of survival among prostate cancer survivors varied by area of residence. Adoption of best practice from areas performing well could support enhanced survival quality in poorer performing areas, particularly with regard to bowel problems and vitality, where clinically relevant differences were reported. PATIENT SUMMARY: We conducted a UK-wide survey of patient's quality of life after treatment for prostate cancer. Outcomes were found to vary depending upon where patients live. Different service providers need to ensure that all prostate cancer patients receive the same follow-up care.
A Prospective, Open Label, Randomized Phase II Trial of Weekly Docetaxel Versus Weekly Vinorelbine as First Line Chemotherapy in Patients With Androgen Independent Prostate Cancer
AbstractPURPOSE: In previous phase I to III studies docetaxel and vinorelbine have shown promising activity in androgen independent prostate cancer. In the present trial we assessed the efficacy and tolerability of single agent low dose docetaxel vs vinorelbine in patients with advanced androgen independent prostate cancer. MATERIALS AND METHODS: A total of 40 chemotherapy naive patients with histologically proven androgen independent prostate cancer, adequate androgen ablation, and clinical and/or biochemical progression were randomly assigned to receive either 25 mg/m(2) docetaxel (arm A) or 25 mg/m(2) vinorelbine (arm B) weekly. Treatment was continued until clinical and/or biochemical progression. In cases of progression patients switched to the alternative treatment arm. The primary end point was time to disease progression. Secondary end points included prostate specific antigen response rates in sequential treatment, analgesic response and toxicity. RESULTS: The current analysis showed a doubled risk of progression in treatment arm B. The median time to first disease progression was 14.5 months for arm A vs 4.4 months for arm B. The proportion of patients with a greater than 50% prostate specific antigen decrease on first line therapy was significantly higher in arm A (62.5%) compared to arm B (11.1%) (p = 0.0033). After progression to docetaxel second line vinorelbine yielded a greater than 50% prostate specific antigen response rate of 28.6% vs 62.5% for second line docetaxel. Clinically significant toxicity occurred more often in arm B with neutropenia grade 4 seen in 22% and grade 3 in 28% of patients (p = 0.0005) during the first treatment phase. CONCLUSIONS: While weekly application of both cytotoxic agents was well tolerated, this study demonstrates the superiority of docetaxel vs vinorelbine as monotherapy in the treatment of androgen independent prostate cancer.
Optimal Sequencing of New Drugs in Metastatic Castration-Resistant Prostate Cancer: Dream or Reality?
AbstractThe availability of new drugs capable of improving the overall survival of patients with metastatic castration-resistant prostate cancer has led to the possibility of using them sequentially in the hope of obtaining a cumulative survival benefit. The new agents have already been administered as third-line treatments in patients who have previously received them as second line in everyday clinical practice, but the efficacy of this practice is not yet supported by clinical trial data, and evidence of possible cross-resistance has reinforced the debate concerning the best sequence to use in order to maximise the benefit. Furthermore, the situation is further complicated by the possibility of administering new hormonal agents to chemotherapy-naïve patients, and novel chemotherapeutic agents to hormone-sensitive patients. This article critically reviews the available data concerning the sequential use of new drugs, and discusses the real evidence concerning their optimal positioning in the therapeutic strategy of metastatic castration-resistant prostate cancer.
The Japanese Journal of Urology · 2021 · 1 citations · open access
COST ANALYSIS OF ANDROGEN DEPRIVATION THERAPY AND DRUGS FOR CASTRATION-RESISTANT PROSTATE CANCER
Abstract(Purpose) Recently, new effective drugs for the treatment of castration-resistant prostate cancer (CRPC) have been developed. Although they are expected to prolong the survival time of patients with advanced prostate cancer, they may result in an economic burden. In this study, we determined the treatment results and the cost of CRPC drugs. (Methods) From 2014 to 2017, patients who were unfit for curative therapy were enrolled in this study. First, they received androgen deprivation therapy (ADT) by surgical or chemical castration. Once castration-sensitive cancer progressed to castration-resistant cancer, CRPC drugs, such as docetaxel, cabazitaxel, abiraterone and enzalutamide, were administered sequentially. In elderly or fragile patients, drug doses were often reduced to minimize their toxicity. The total costs of drugs for castration-sensitive and castration-resistant cancers were calculated, and the results were evaluated. (Results) Prostate biopsies detected prostate cancer in 257 patients. Eighty-one patients were treated with ADT, and 56 of the cancers were metastatic or showed a high prostate specific antigen level (>100 ng/ml). Thirty patients out of the 56 with advanced cancers developed CRPC, and the median time to CRPC was 10 months (range, 3-39). Drugs targeting CRPC were administered in 25 patients for a median duration of 20 months (range, 3-50). During the median observation period of 48 months (range, 13-75), 15 patients died of prostate cancer. The median annual cost of drugs for castration-sensitive cancer was 234,000 Japanese yen (2,187 US dollars) [range, 50,000-315,000 yen (467-2,943 US dollars) ]. In contrast, the median annual cost of drugs for CRPC was 2,041,000 yen (19,075 US dollars) [range, 346,000-5,017,000 yen (3,230-46,886 US dollars) ]. (Conclusions) Advanced prostate cancer tended to rapidly progress to CRPC, which required a sequence of expensive drugs for treatment. Early diagnosis preventing the development of advanced prostate cancer is desirable to reduce the economic burden for the health insurance system.
UroCancer Clinics of India . · 2024 · 0 citations · open access
Controversies in Management of Localized Prostate Cancer: Before and After Radical Local Therapy
AbstractSummary The therapeutic world of prostate cancer has evolved a lot in the last decade. Initially, we have only androgen deprivation therapies, earlier generation androgen receptor pathway inhibitor (ARPI), and chemotherapy. Now, we have multiple other options, and also there are ample data in all the spaces of its management. However, some areas need discussion, as controversies exist. In this review, we would like to throw some light on such controversial real in dealing with the biochemical recurrence after radical local therapy (RLT) and neoadjuvant treatment before RLT. We envisage to clear the cloud as per the existing literature.
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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