DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for prostate neoplasm — screening already-approved drugs against its 21-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleProstate neoplasm maps to a 21-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
approvedCabazitaxelApproved drugapprovedDarolutamideAndrogen Receptor antagonistapprovedLutetium Lu-177 Vipivotide TetraxetanGlutamate carboxypeptidase II binding agent · DNA disrupting agent
Structures already discussed alongside prostate neoplasm 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 1b (TUBA1B) — TUBA1B is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has guanosine-5'-triphosphate bound in it, shown as sticks.
Loading structure…
helix sheet gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6S8L · 1.801 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
In a phase 3 trial of 1509 men with non-metastatic, castration-resistant prostate cancer, darolutamide extended median metastasis-free survival to 40.4 months compared with 18.4 months on placebo (hazard ratio for metastasis or death 0.41, 95% CI 0.34 to 0.50). A 2023 review describes darolutamide as one of the most effective and safe drugs for metastatic hormone-sensitive prostate cancer when used in combination with androgen deprivation therapy, but provides no new numerical data from that review.
Cabazitaxel was studied in an Italian early-access programme of 218 docetaxel-pretreated patients with metastatic castration-resistant prostate cancer, who received 25 mg/m² every three weeks plus prednisolone. The median number of cycles was six. Grade 3/4 neutropenia occurred in 33.9% of patients, leukopenia in 15.6%, anaemia in 6%, and asthenia in 6%. No peripheral neuropathy or nail disorders were reported. A separate French retrospective study of 22 patients who received three or more lines of cabazitaxel reported median overall survival from metastatic castration-resistant prostate cancer diagnosis of 105 months. Median progression-free survival from the start of each cabazitaxel line was 11.8 months at first use, 9.6 months at first rechallenge, and 5.6 months at second rechallenge. Only one case of febrile neutropenia and six grade 3 or higher toxicity events were reported in that cohort.
Lutetium Lu 177 vipivotide tetraxetan was FDA-approved in March 2022 for adults with PSMA-positive metastatic castration-resistant prostate cancer who have at least one metastatic lesion. Two phase 3 trials support its use after progression on an androgen receptor pathway inhibitor with or without docetaxel, showing improved radiographic progression-free survival. The VISION study reported median overall survival of 15.3 months. A retrospective review of 34 patients treated at West Virginia University Health Science Center between July 2022 and February 2024 found a median overall survival of 10 months from the first dose, which the authors note did not match the VISION result. Of those patients, 53% were alive at the time of analysis, 41% completed six cycles, and 91% were Caucasian. The median time from initial prostate cancer diagnosis to first dose was 67 months. The review also notes that kidney excretion may increase renal toxicity in patients with reduced renal function, and that common side effects include asthenia, dry mouth, mild nausea, and low-grade anaemia.
What remains missing are prospective data from diverse, non-trial populations to explain the survival gap between the VISION trial and the West Virginia real-world experience. No biomarker has been validated to predict which patients will benefit from cabazitaxel rechallenge. The optimal timing of lutetium Lu 177 vipivotide tetraxetan within the treatment sequence, and whether earlier use or combination with other agents improves outcomes, is still under investigation.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Future Oncology · 2013 · 51 citations · open access
Real-world Cabazitaxel Safety: The Italian Early-Access Program in Metastatic Castration-Resistant Prostate Cancer
AbstractAIM: Cabazitaxel is a novel taxane that is approved for use in metastatic castration-resistant prostate cancer based on the Phase III TROPIC study, which showed improved overall survival with cabazitaxel/prednisone versus mitoxantrone/prednisone. A global early-access program was initiated in order to provide early access to cabazitaxel in docetaxel-pretreated patients and to obtain real-world data. PATIENTS & METHODS: We report interim safety results from an Italian prospective, single-arm, multicenter, open-label trial of 218 patients receiving cabazitaxel 25 mg/m2 every 3 weeks plus prednisolone 10 mg/day, until disease progression, unacceptable toxicity, investigator's decision or death. RESULTS: Patients completing treatment received a median of six cabazitaxel cycles. The most common grade 3/4 adverse events were neutropenia (33.9%), leukopenia (15.6%), anemia (6%) and asthenia (6%). No peripheral neuropathy or nail disorders were observed. CONCLUSION: These results confirm that cabazitaxel has a manageable safety profile in daily clinical practice and support its use in patients with prostate cancer who progress during or after a docetaxel-based therapy.
Yearbook of pediatric endocrinology · 2019 · 18 citations
Darolutamide in nonmetastatic, castration-resistant prostate cancer
AbstractThis paper reports a randomized, double-blind, placebo-controlled, phase 3 trial of darolutamide, a novel oral androgen-receptor antagonist, in 1509 men with non-metastatic, castration-resistant prostate cancer. Median metastasis-free survival was significantly longer with darolutamide (40.4 months) than placebo (18.4 months; hazard ratio for metastasis or death: 0.41; 95% CI, 0.34 to 0.50; P<0.001).
Lutetium Lu 177 vipivotide tetraxetan for prostate cancer
AbstractOn March 23, 2022, the U.S. Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan), also known as 177Lu-PSMA-617, for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who have highly expressed prostate-specific membrane antigen (PSMA) and have at least one metastatic lesion. It is the first FDA-approved targeted radioligand therapy for eligible men with PSMA-positive mCRPC. Lutetium Lu 177 vipivotide tetraxetan is a radioligand that strongly binds to PSMA, making it ideal for treating cancers of the prostate by targeted radiation, resulting in DNA damage and cell death. PSMA is overexpressed in cancer cells while being lowly expressed in normal tissues, which makes it an ideal theranostic target. As precision medicine advances, this is a thrilling turning point for highly individualized treatments. This review aims to summarize the pharmacology and clinical studies of the novel drug lutetium Lu 177 vipivotide tetraxetan for the treatment of mCRPC, emphasizing its mechanism of action, pharmacokinetics and safety.
Novel PSMA-Targeting Radionuclide Peptidomimetics for Treating Prostate Cancer
AbstractProstate cancer is the third-most commonly diagnosed cancer and is one of the leading causes of cancer-related deaths in men worldwide. Although an armamentarium of approved drugs exists, treatment options become severely limited when resistance develops against last-line taxane chemotherapeutics. In March 2022, the FDA approved a first-in-class targeted radionuclide therapy, lutetium Lu 177 vipivotide tetraxetan (Pluvicto), for treating metastatic castration-resistant prostate cancer. The drug constitutes a prostate-specific membrane antigen-targeting peptidomimetic moiety conjugated to a radionuclide chelator via a linker. This Patent Highlight reveals the structure–activity relationship of key compounds against prostate cancer cells.
Cabazitaxel multiple rechallenge in metastatic castration-resistant prostate cancer: A therapeutic option to increase overall survival?
Abstract97 Background: Cabazitaxel rechallenge could be a more efficient therapy with an acceptable toxicity than docetaxel in the treatment of patients with a metastatic castration resistant prostate cancer (mCRPC). The aim of this study was to assess the feasibility and efficacy of cabazitaxel multiple rechallenge. Methods: This is a multicenter, retrospective cohort study including patients from 9 centers in France who received 3 lines or more of cabazitaxel from February 2012 to July 2020. Cabazitaxel schedule differed between patients: 25 mg/m 2 q3w, 20 mg/m 2 q3w, 16 mg/m 2 q2w or 10 mg/m 2 weekly. Efficacy was assessed by overall survival (OS) and progression-free survival (PFS) from each cabazitaxel line start. Only toxicities grade ≥ 3 were reported. Results: Twenty-two patients were included. The median follow-up from mCRPC was 94.7 months, median age at initial diagnosis was 59.5 years old, median ISUP score at diagnosis was 4 and median PSA at diagnosis was 55 ng/ml. Median number of cabazitaxel cycles was 7 at first-line, 6 at first rechallenge, and 5 for subsequent rechallenges. Median OS from mCRPC diagnosis was 105 months. Median PFS from cabazitaxel line start was 11.8 months at first use, 9.6 for first rechallenge and 5.6 in second rechallenge (table). Only one case of febrile neutropenia and 6 events of grade ≥ 3 toxicity were reported. Conclusions: Cabazitaxel multiple rechallenge could efficiently extend OS with manageable toxicities for patients. Even if anti-PARP therapy and immunotherapy are promising treatments, cabazitaxel rechallenge could be also a relevant therapeutic option for long responder patients. Specific biomarkers should be explored to predict the efficacy of cabazitaxel rechallenge. [Table: see text]
Effectiveness and safety of darolutamide as a component of combination therapy in patients with prostate cancer
AbstractProstate cancer is an extremely important problem in current urologic oncology. For a long time, the golden standard of treatment of common forms of prostate cancer at the stage of distant metastases was androgen deprivation therapy directed at suppression of native testosterone level. Combination treatment using long-term androgen deprivation therapy and new generation antiandrogens is currently a scientifically substantiated conceptually new standard of therapy which has replaced treatment paradigm using androgen deprivation therapy as a monotherapy in patients with metastatic hormone-sensitive prostate cancer. The article presents the results of large trials performed in patients with metastatic hormone-sensitive prostate cancer and characterizes the role of one of the most effective and safe drugs, darolutamide, used to treat patients of this subgroup.
Lutetium-177–PSMA-617 experience in Appalachian patients with advanced prostate cancer at West Virginia University Health Science Center.
Abstracte17045 Background: Lutetium Lu-177 vipivotide tetraxetan (Lu-177) allowed for improved biochemical and radiographic response rate with relatively low toxicity for metastatic castration-resistant prostate cancer (PC) after multiple lines of therapy. In the 2021 VISION study (DOI: 10.1056/NEJMoa2107322), Lu-177 was reported to have a median overall survival (OS) of 15.3 months in patients (pts) with advanced prostate cancer (PC). We reviewed the result with Lu-177 for the treatment of advanced PC at a rural tertiary academic center at West Virginia University Health Science Center (WVU-HSC). Methods: All PC pts receiving one or more doses of Lu-177 at WVU-HSC were retrospectively reviewed. Pts were followed until death or the last clinic visit. All pts were established patients at WVU-HSC for management of the advanced PC between July 2022 and February 2024. Data was tabulated with descriptive statistics and median survival was calculated from Kaplan-Meier method. Results: Over an eighteen months period 34 pts received 126 doses of Lu-177. 26 pts were referred from outside the WVU-HSC specifically for Lu-177. Demographics from data collection showed predominantly Caucasian pts (91% Caucasian). The time from the initial PC diagnosis to the first dose of Lu-177 was a median of 67 months (range: 10 months-367 months). The median age at the first dose of Lu-177 was 65 years (range: 45-80). 18 patients (53%) remain alive as of Feb 2024. 14 pts (41%) completed 6 cycles of Lu-177 and 11 pts (32%) remain alive. The Kaplan-Meier median OS for these 34 pts starting from the first cycle of Lu-177 was 10 months. Conclusions: A 2022 estimated cost for Lu-177 was $42,500 per dose (excludes administration) so “payors” may have been charged more than $5,000,000 for the Lu-177 for these patients. Lu-177 may be of more benefit earlier in the PC disease spectrum, or perhaps pre-treatment PSMA imaging can better target patients who will benefit from Lu-177. Our observed median OS of 10 months did not match the 15.3 reported in the VISION study (DOI: 10.1056/NEJMoa2107322). Further data evaluation and collection are warranted from different communities to investigate the differences observed in the survival data reported in the literature and observed in the clinic setting. [Table: see text]
Journal of Oncology Pharmacy Practice · 2025 · 0 citations
Lutetium Lu 177 vipivotide tetraxetan: A literature review
AbstractTo review pharmacology, pharmacokinetics, therapeutic use, product safety/description and perspectives on use of lutetium Lu 177 vipivotide tetraxetan in patients with metastatic castration-resistant prostate cancer (mCRPC). Data sources: A literature search was conducted using PubMed/Dynamed (October 2013-May 2025), limited to English language, humans, clinical trials, case reports, and guidelines. Data summary: Lutetium Lu 177 vipivotide tetraxetan is comprised of the beta-emitting radioisotope lutetium Lu-177 linked to a peptide, vipivotide tetraxetan, which binds to cells expressing prostate-specific membrane antigen (PSMA), resulting in cell death from the radiation. Kidney excretion may result in increased renal toxicity in patients with reduced renal function. Based on 2 phase III clinical trials, lutetium Lu 177 vipivotide tetraxetan 7.4 GBq administered intravenously every 6 weeks for up to 6 doses is effective in patients with mCRPC and PSMA-positive metastases after progressing on an androgen receptor pathway inhibitor and docetaxel therapy or an androgen receptor pathway inhibitor alone, by significantly improving radiographic progression-free survival. It is generally well tolerated, with asthenia/fatigue, dry mouth, mild nausea and low-grade anemia most commonly occurring. Severe adverse drug reactions are uncommon. It should only be administered by trained personnel in a designated clinical setting with existing radiation safety protocols. Patients must limit close contact, use precautions with using the bathroom and other daily activities in days following treatment. Patient education is necessary to ensure safe daily practices. Several ongoing trials are evaluating lutetium Lu 177 vipivotide tetraxetan in combination with other anticancer agents for treatment of mCRPC, using different dosing strategies, or in other settings (metastatic castration-sensitive prostate cancer and early-stage prostate cancer). Conclusion: Lutetium Lu 177 vipivotide tetraxetan is an effective and well tolerated treatment for patients with mCRPC, PSMA-positive metastases after progressing on an androgen receptor pathway inhibitor ± docetaxel. Ongoing studies evaluating its use in earlier disease stages and with different dosing strategies, will better define the role of this therapy in the treatment of prostate cancer.
Disease module: DeepOracle (Open Targets). Approved indication: ChEMBL drug_indication (max_phase=4). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works, 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.
