DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for pancreatic carcinoma — screening already-approved drugs against its 47-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePancreatic carcinoma maps to a 47-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
approvedEverolimusApproved drugapprovedPaclitaxelApproved drug
Structures already discussed alongside pancreatic carcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Cytochrome P450 107G1 (RapN) — Everolimus has a real, experimentally solved structure in complex with this target (PDB 6L3A, 3.0 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 e53drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6L3A · 3.0 Å · ligand Everolimus (E53). Experimental structure, not a prediction.
What the evidence adds up to
A 2013 meta-analysis of 16 studies covering 1,308 patients with advanced pancreatic cancer treated with gemcitabine plus erlotinib reported weighted 1-year survival of 27.9%, objective response rate of 9.1%, and disease control rate of 57.0%. Median progression-free survival ranged from 2 to 9.6 months, median overall survival from 5 to 12.5 months. Compared with gemcitabine alone, the combination gave significantly longer progression-free and overall survival, but also more deaths and interstitial lung disease-like syndrome. A separate 2013 phase II trial in 69 chemotherapy-naïve Korean patients found an objective response rate of 18.8%, tumour stabilisation rate of 49.2%, median overall survival of 7.7 months, and median progression-free survival of 1.9 months. A 2010 retrospective review of 20 Chinese patients reported no complete or partial remissions, 55% stable disease, median progression-free survival of 4.0 months, and median overall survival of 8 months.
A 2018 real-world analysis of 321 metastatic pancreatic cancer patients compared two time periods: 2011–2013 (when gemcitabine monotherapy was preferred) and 2014–2016 (when gemcitabine plus nab-paclitaxel was preferred). Response rates were 7.8% versus 28.4%, median progression-free survival 3.1 versus 5.4 months, and median overall survival 6.7 versus 10.2 months; all differences were statistically significant. A 2013 retrospective study of 20 heavily pretreated patients who received nab-paclitaxel monotherapy after progression on gemcitabine (40% had also received FOLFIRINOX) reported stable disease in 64.7% of 17 evaluable patients, median progression-free survival of 3.7 months, and median overall survival of 5.2 months. A 2010 phase II trial of paclitaxel plus the protein kinase C inhibitor bryostatin-1 in 19 patients with advanced pancreatic adenocarcinoma found no confirmed objective responses; median time to treatment failure was 1.9 months, and 74% discontinued due to progression or death.
For pancreatic neuroendocrine tumours, a 2012 subgroup analysis of 23 Japanese patients from the RADIANT-3 trial reported that everolimus 10 mg/day prolonged median progression-free survival to 19.45 months versus 2.83 months with placebo, an 81% risk reduction. All 23 patients on everolimus experienced adverse drug reactions, most commonly rash (87%), stomatitis (74%), infections (65%), nail disorders (52%), epistaxis (44%), and pneumonitis (44%). A 2017 case report described one patient with a giant pancreatic neuroendocrine tumour and portal vein thrombus who became resectable after two years of everolimus and remained recurrence-free for 27 months after surgery.
What is still missing: prospective trials that stratify patients by tumour biology (exocrine versus neuroendocrine, mutational status, prior treatment line) rather than lumping all advanced pancreatic cancer together; adequately powered studies of nab-paclitaxel monotherapy in the refractory setting; and funding for trials that test drug combinations against the current standard regimens rather than against placebo or older monotherapies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PLoS ONE · 2013 · 65 citations · open access
Gemcitabine Plus Erlotinib for Advanced Pancreatic Cancer: A Systematic Review with Meta-Analysis
AbstractBACKGROUND: This study aims to comprehensively summarize the currently available evidences on the efficacy and safety of gemcitabine plus erlotinib for treating advanced pancreatic cancer. METHODOLOGY/PRINCIPAL FINDINGS: PubMed, EMBASE, The Cochrane Library and abstracts of recent major conferences were systematically searched to identify relevant publications. Studies that were conducted in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib (with or without comparison with gemcitabine alone) and reporting objective response rate, disease control rate, progression-free survival, time-to-progression, overall survival, 1-year survival rate and/or adverse events were included. Data on objective response rate, disease control rate, 1-year survival rate and adverse events rate, respectively, were combined mainly by using Meta-Analyst software with a random-effects model. Data on progression-free survival, time-to-progression and overall survival were summarized descriptively. Sixteen studies containing 1,308 advanced pancreatic cancer patients treated with gemcitabine plus erlotinib were included. The reported median progression-free survival (or time-to-progression), median overall survival, 1-year survival rates, objective response rates and disease control rates were 2-9.6 months, 5-12.5 months, 20%-51%, 0%-28.6% and 25.0%-83.3%, respectively. The weighted 1-year survival rate, objective response rate and disease control rate based on studies reporting robust results were 27.9%, 9.1% and 57.0%, respectively. According to the studies with relevant data, the incidences of total and severe adverse events were 96.3% and 62.9%, respectively. The most frequently reported adverse events were leucopenia, rash, diarrhea, vomitting, neutropenia, thrombocytopenia, anaemia, stomatitis, drug-induced liver injury, fatigue and fever. Compared with gemcitabine alone, the progression-free survival and overall survival with gemcitabine plus erlotinib were significantly longer, but there were also more deaths and interstitial lung disease-like syndrome related to this treatment. CONCLUSIONS/SIGNIFICANCE: Gemcitabine plus erlotinib represent a new option for the treatment of advanced pancreatic cancer, with mild but clinically meaningful additive efficacy compared with gemcitabine alone. Its safety profile is generally acceptable, although careful management is needed for some specific adverse events.
Japanese Journal of Clinical Oncology · 2012 · 51 citations · open access
Everolimus for Advanced Pancreatic Neuroendocrine Tumours: A Subgroup Analysis Evaluating Japanese Patients in the RADIANT-3 Trial
AbstractOBJECTIVE: Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65% risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study. METHODS: Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions. RESULTS: Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95% confidence interval, 8.31-not available) with everolimus vs 2.83 months (95% confidence interval, 2.46-8.34) with placebo, resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95% confidence interval, 0.08-0.48; P< 0.001). Adverse drug reactions occurred in all 23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17; 74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10; 44%) and pneumonitis (n = 10; 44%). CONCLUSIONS: These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours.
American Journal of Clinical Oncology · 2010 · 41 citations · open access
Phase II Study of Paclitaxel Plus the Protein Kinase C Inhibitor Bryostatin-1 in Advanced Pancreatic Carcinoma
AbstractPURPOSE: To determine the efficacy and toxicity of the protein kinase C inhibitor bryostatin-1 plus paclitaxel in patients with advanced pancreatic carcinoma. METHODS: Each treatment cycle consisted of paclitaxel 90 mg/m by intravenous infusion over 1 hour on days 1, 8, and 16, plus bryostatin 25 mcg/m as a 1-hour intravenous infusion on days 2, 9, and 15, given every 28 days. Patients were evaluated for response after every 2 treatment cycles, and continued therapy until disease progression or prohibitive toxicity. The primary objective was to determine whether the combination produced a response rate of at least 30%. RESULTS: Nineteen patients with locally advanced or metastatic pancreatic adenocarcinoma received a total of 52 cycles of therapy (range: 1-10). Patients received the combination as first-line therapy for advanced disease (N = 5) or after prior chemotherapy used alone or in combination with local therapy. No patients had a confirmed objective response. The median time to treatment failure was 1.9 months (95% confidence intervals: 1.2, 2.6 months). Reasons for discontinuing therapy included progressive disease or death in 14 patients (74%) or because of adverse events or patient choice in 5 patients (26%). The most common grade 3 to 4 toxicities included leukopenia in 26%, anemia in 11%, myalgias in 11%, gastrointestinal bleeding in 11%, infection in 10%, and thrombosis in 10%. CONCLUSION: The combination of weekly paclitaxel and bryostatin-1 is not an effective therapy for patients with advanced pancreatic carcinoma.
Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis
AbstractBACKGROUND/AIM: FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) and gemcitabine plus nab-paclitaxel therapy have recently been introduced for the treatment of metastatic pancreatic cancer. Herein, overall treatment outcomes of metastatic pancreatic cancer after introduction of FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy were evaluated, in daily practice. PATIENTS AND METHODS: Metastatic pancreatic cancer patients (n=321) who started systemic chemotherapy between January 2011 and December 2016 were included and were divided into two groups: group A (2011-2013) and group B (2014-2016). Treatment outcomes were evaluated retrospectively. RESULTS: Patient characteristics were similar between the two groups except for the rates of distant lymph node metastasis and peritoneal metastasis. The preferred regimens in groups A and B were gemcitabine monotherapy and gemcitabine plus nab-paclitaxel therapy, respectively. The response rates, median progression-free survival, and median overall survival of groups A and B were 7.8% and 28.4% (p<0.01), 3.1 months and 5.4 months (p<0.01), and 6.7 months and 10.2 months (p<0.01), respectively. CONCLUSION: Overall treatment outcomes for metastatic pancreatic cancer were significantly improved after introduction of FOLFIRINOX and gemcitabine plus nab-paclitaxel combination therapy in daily practice.
Nab-paclitaxel monotherapy in refractory pancreatic adenocarcinoma.
AbstractBACKGROUND: The standard of care in patients with metastatic pancreatic adenocarcinoma is undefined beyond second line of treatment. There have been scant reports of benefit from nab-paclitaxel in patients with refractory pancreatic cancer. MATERIALS AND METHODS: A retrospective review was carried out in patients with pancreatic adenocarcinoma at Siteman Cancer Center, who had received nab-paclitaxel monotherapy after experiencing disease progression on standard treatments. Nab-paclitaxel was given either two out of every three weeks or three out of every four weeks. RESULTS: Twenty patients were identified and included for data analysis. Median age was 63.5 years old. All patients had previously received gemcitabine, while 40% had also received FOLFIRINOX. Median number of prior lines of systemic treatment was 2. Patients were treated for a median of 15 weeks, with a range of 1 to 41.7 weeks. Median dose of nab-paclitaxel was 100 mg/m(2) with range of 75-125 mg/m(2). Best response imaging was available in 17 patients and 11 out of the 17 patients (64.7%) had stable disease. Median progression-free survival (PFS) was 3.7 months and overall survival (OS) were 5.2 months. Most common treatment related toxicities included grade 1 pneumonitis in five patients (25%), grade 3 or 4 neutropenia in three patients (15%), and dehydration resulting in hospitalization in one patient (5%). CONCLUSIONS: Nab-paclitaxel monotherapy had acceptable level of toxicity in a heavily pretreated patient population with pancreatic cancer and appeared to provide a clinical benefit. This agent is worthy of further prospective studies to evaluate extent of benefit after standard therapies have failed.
Phase II Trial of Erlotinib Plus Gemcitabine Chemotherapy in Korean Patients with Advanced Pancreatic Cancer and Prognostic Factors for Chemotherapeutic Response
AbstractBACKGROUND/AIMS: Erlotinib and gemcitabine combined chemotherapy is becoming the treatment of choice in advanced pancreatic cancer. We evaluated the effectiveness of treatment with erlotinib plus gemcitabine and the prognostic factors for chemotherapeutic response in Korean pancreatic cancer patients. METHODS: Sixty-nine patients with advanced pancreatic cancer who were treated with daily erlotinib 100 mg orally and gemcitabine 1,000 mg/m(2)/30 min intravenous infusion on days 1, 8, and 15 of each 4-week cycle from 2006 to 2009 were included in this study. This study was a phase II single-center trial. RESULTS: All 69 patients with advanced pancreatic cancer were chemotherapy-naïve. The objective response rate was 18.8%, and the overall tumor-stabilization rate was 49.2%. The median overall survival was 7.7 months (95% confidence interval [CI], 6.0 to 9.4 months). The median progression-free survival was 1.9 months (95% CI, 1.4 to 2.5 months). Prognostic factors for good chemotherapeutic response were good performance status and the presence of skin rash during chemotherapy. Patients with lower performance scores showed worse chemotherapeutic responses (odds ratio [OR], 7.6; 95% CI, 2.4 to 24.8). Poor responses were predicted by the absence of skin rash during chemotherapy (OR, 3.0; 95% CI, 1.4 to 6.3). CONCLUSIONS: Erlotinib and gemcitabine chemotherapy is a tolerable treatment regimen and has a favorable therapeutic effect in Korean patients with advanced pancreatic cancer.
Surgical Case Reports · 2017 · 9 citations · open access
A case of successful conversion from everolimus to surgical resection of a giant pancreatic neuroendocrine tumor
AbstractBACKGROUND: Although pancreatic neuroendocrine tumors generally have a far better prognosis relative to pancreatic cancer, the varied manifestations lead to treatment-related challenges. Everolimus therapy is generally recommended for patients with advanced pancreatic neuroendocrine tumors; however, its efficacy in a neoadjuvant setting remains unclear. Here we present a case of a giant pancreatic neuroendocrine tumor with a portal tumor thrombus that became resectable after everolimus therapy. CASE PRESENTATION: A 62-year-old woman was admitted to our hospital for surgical resection of a giant pancreatic neuroendocrine tumor in the left upper abdomen. Unfortunately, she was ineligible for surgery because the tumor had extended near the hepatic hilus in the portal vein, and she was administered everolimus (10 mg/day). After 2 years of this therapy, the extent of portal vein involvement had decreased, despite the lack of significant changes in the tumor size, and the hepatic hilus became free of disease. She was subsequently referred to us for resection via distal pancreatectomy with portal vein reconstruction because the tumor had begun to grow slowly. Pathological review identified a grade 2 neuroendocrine tumor with no lymph node metastasis. The patient's postoperative course was uneventful, and she has remained recurrence-free for 27 months, despite a lack of additional treatment. CONCLUSIONS: Our experience suggests that everolimus could be useful for neoadjuvant therapy in cases of locally advanced pancreatic neuroendocrine tumor.
[Efficacy of gemcitabine combined with erlotinib in patients with advanced pancreatic cancer].
AbstractOBJECTIVE: To evaluate the efficacy,clinical benefits and toxicities of gemcitabine combined with erlotinib for advanced pancreatic cancer. METHOD: Clinical data of 20 patients with advanced pancreatic cancer treated with gemcitabine 1000 mg/m2 on day 1 and day 8 (repeated every 21 days) plus erlotinib 100-150 mg/d at Peking Union Medical College Hospital was reviewed retrospectively. RESULTS: No patient achieved complete remission or partial remission, 11 patients (55%) had stable disease, and 9 patients (45%) experienced disease progression. The disease control rate was 55%, and clinical benefit rate was 30%. The median progression free survival was 4.0 months, and the median overall survival was 8 months. The total incidence of hematologic toxicity was 70%, including 15% of grade 3-4 leucopenia and 5% of grade 3-4 thrombocytopenia. Eleven patients (55%) had rash, which were all grade 1-2. One patient had grade 2 diarrhea and five had grade 1 transaminase elevation. No chemotherapy-related death occurred. CONCLUSIONS: Gemcitabine combined with erlotinib is an effective regimen for pancreatic cancer with good clinical tolerance. The most common adverse events are hematologic toxicities and rash.
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.
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