DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for colorectal adenocarcinoma — 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 moduleColorectal adenocarcinoma 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
approvedCapecitabineApproved drug
Structures already discussed alongside colorectal adenocarcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
NRAS proto-oncogene, GTPase (NRAS) — NRAS 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'-diphosphate bound in it, shown as sticks.
Loading structure…
helix sheet gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ZIO · 1.55 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
In 329 patients with irinotecan-refractory metastatic colorectal cancer, cetuximab plus irinotecan produced a response rate of 22.9% versus 10.8% for cetuximab alone. Median time to progression was 4.1 months versus 1.5 months. Median survival was 8.6 months versus 6.9 months, a difference that was not statistically significant (P=0.48). In a separate trial of 572 patients previously treated with fluoropyrimidine, irinotecan and oxaliplatin, cetuximab plus best supportive care improved median overall survival to 6.1 months versus 4.6 months with supportive care alone (hazard ratio for death 0.77, P=0.005). Partial responses occurred in 8.0% of cetuximab patients and in none of the controls. A rash of grade 2 or higher was strongly associated with improved survival (hazard ratio 0.33, P<0.001). Adverse events of grade 3 or higher occurred in 78.5% of the cetuximab group versus 59.1% of controls.
A meta-analysis of ten randomised controlled trials (6977 patients) found that bevacizumab improved overall survival (hazard ratio 0.848, 95% CI 0.747–0.963), progression-free survival (hazard ratio 0.617, 95% CI 0.530–0.719), and overall response rate (odds ratio 1.627, 95% CI 1.199–2.207). Higher rates of grade 3 or higher hypertension, proteinuria, bleeding, thrombosis and gastrointestinal perforation were observed, though the incidence of serious toxicity was described as very low. In a phase II study of 59 elderly patients (mean age 76) receiving first-line capecitabine plus bevacizumab, partial response was 33.3%, stable disease 59.0%, and median progression-free survival 10.8 months. Four patients died due to toxicity (mucositis, digestive haemorrhage, haematological toxicity and sepsis).
A phase II study of lapatinib plus capecitabine in 29 patients with refractory colorectal adenocarcinoma reported no complete or partial responses. Stable disease was achieved in 41.4% of patients. Median overall survival was 6.8 months, median progression-free survival 2.1 months. The authors concluded the regimen was not effective. A systematic review of cetuximab cost-effectiveness noted that its broader clinical effectiveness is subject to ongoing debate and that its cost-effectiveness compared with bevacizumab or standard chemotherapy regimens remains contested. In a rat model, intraperitoneal cetuximab given 24 hours after colonic anastomosis reduced adhesion formation without impairing healing, whereas peroperative administration decreased both hydroxyproline levels and bursting pressure.
What is still missing: prospective trials that stratify patients by KRAS and other biomarkers, direct randomised comparisons of cetuximab and bevacizumab in defined lines of therapy, and formal cost-effectiveness analyses that incorporate quality-of-life data from elderly and frail populations.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2004 · 5055 citations · open access
Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer
AbstractBACKGROUND: The epidermal growth factor receptor (EGFR), which participates in signaling pathways that are deregulated in cancer cells, commonly appears on colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We compared the efficacy of cetuximab in combination with irinotecan with that of cetuximab alone in metastatic colorectal cancer that was refractory to treatment with irinotecan. METHODS: We randomly assigned 329 patients whose disease had progressed during or within three months after treatment with an irinotecan-based regimen to receive either cetuximab and irinotecan (at the same dose and schedule as in a prestudy regimen [218 patients]) or cetuximab monotherapy (111 patients). In cases of disease progression, the addition of irinotecan to cetuximab monotherapy was permitted. The patients were evaluated radiologically for tumor response and were also evaluated for the time to tumor progression, survival, and side effects of treatment. RESULTS: The rate of response in the combination-therapy group was significantly higher than that in the monotherapy group (22.9 percent [95 percent confidence interval, 17.5 to 29.1 percent] vs. 10.8 percent [95 percent confidence interval, 5.7 to 18.1 percent], P=0.007). The median time to progression was significantly greater in the combination-therapy group (4.1 vs. 1.5 months, P<0.001 by the log-rank test). The median survival time was 8.6 months in the combination-therapy group and 6.9 months in the monotherapy group (P=0.48). Toxic effects were more frequent in the combination-therapy group, but their severity and incidence were similar to those that would be expected with irinotecan alone. CONCLUSIONS: Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory colorectal cancer.
New England Journal of Medicine · 2007 · 1807 citations · open access
Cetuximab for the Treatment of Colorectal Cancer
AbstractBACKGROUND: Cetuximab, an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor (EGFR), has activity against colorectal cancers that express EGFR. METHODS: From December 2003 to August 2005, 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine, irinotecan, and oxaliplatin or had contraindications to treatment with these drugs underwent randomization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care (287 patients) or best supportive care alone (285 patients). The primary end point was overall survival. RESULTS: In comparison with best supportive care alone, cetuximab treatment was associated with a significant improvement in overall survival (hazard ratio for death, 0.77; 95% confidence interval [CI], 0.64 to 0.92; P=0.005) and in progression-free survival (hazard ratio for disease progression or death, 0.68; 95% CI, 0.57 to 0.80; P<0.001). These benefits were robust after adjustment in a multivariable Cox proportional-hazards model. The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone. Partial responses occurred in 23 patients (8.0%) in the cetuximab group but in none in the group assigned to supportive care alone (P<0.001); the disease was stable in an additional 31.4% of patients assigned to cetuximab and in 10.9% of patients assigned to supportive care alone (P<0.001). Quality of life was better preserved in the cetuximab group, with less deterioration in physical function and global health status scores (both P<0.05). Cetuximab treatment was associated with a characteristic rash; a rash of grade 2 or higher was strongly associated with improved survival (hazard ratio for death, 0.33; 95% CI, 0.22 to 0.50; P<0.001). The incidence of any adverse event of grade 3 or higher was 78.5% in the cetuximab group and 59.1% in the group assigned to supportive care alone (P<0.001). CONCLUSIONS: Cetuximab improves overall survival and progression-free survival and preserves quality-of-life measures in patients with colorectal cancer in whom other treatments have failed. (ClinicalTrials.gov number, NCT00079066 [ClinicalTrials.gov].).
World Journal of Gastroenterology · 2015 · 82 citations · open access
Value of bevacizumab in treatment of colorectal cancer: A meta-analysis
AbstractAIM: To assess the efficacy and safety of bevacizumab in the treatment of colorectal cancer. METHODS: All randomized controlled trials of bevacizumab for the treatment of colorectal cancer from January 2003 to June 2013 were collected by searching the Cochrane Library, PubMed, Chinese National Knowledge Infrastructure and Wanfang databases. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival, overall response rate and adverse events. Two reviewers extracted data independently. Statistical analyses were performed with Stata 12.0. The degree of bias was assessed using funnel plots for the effect size of OS at the primary endpoint. RESULTS: Following the inclusion criteria and exclusion criteria, ten studies comprising 6977 cases were finally included, of which nine were considered to be of high quality (4-7 points) and one of low quality (1-3 points). Our meta-analysis revealed the efficacy of bevacizumab in patients with colorectal cancer in terms of OS (HR = 0.848, 95%CI: 0.747-0.963), progression-free survival (HR = 0.617, 95%CI: 0.530-0.719), and overall response rate (OR = 1.627, 95%CI: 1.199-2.207). Regarding safety, higher rates of grade ≥ 3 hypertension, proteinuria, bleeding, thrombosis, and gastrointestinal perforation were observed in the bevacizumab treatment group (P < 0.05); however, the incidence of serious toxicity was very low. There was no publication bias in the 10 reports included in this meta-analysis. CONCLUSION: The clinical application of bevacizumab in colorectal cancer is effective with good safety.
A phase II study of capecitabine and lapatinib in advanced refractory colorectal adenocarcinoma: A Wisconsin Oncology Network study.
AbstractBACKGROUND: Prognosis remains poor after progression on first-line chemotherapy for colorectal adenocarcinoma, and inactivation of the EGFR pathway with monoclonal antibodies is an effective treatment strategy in selected patients with metastatic disease. Lapatinib is an oral EGFR and HER-2 dual tyrosine kinase inhibitor that has not shown significant activity in metastatic colorectal cancer. However, lapatinib may act synergistically with capecitabine in anticancer effects. METHODS: This was an open-label, non-randomized phase II study of lapatinib 1,250 mg orally daily and capecitabine 2,000 mg/m(2) by mouth split into twice-daily dosing for 14 days of a 21 days cycle. Inclusion criteria included metastatic or locally advanced adenocarcinoma of the colon or rectum with progression by RECIST on or within six months of receiving a fluoridopyrimidine-, oxaliplatin- or irinotecan-containing regimen. Prior EGFR monoclonal antibody was permitted. K-ras testing was not routinely performed and was not a part of the study protocol. RESULTS: Twenty nine patients (16 M; 13 F) were enrolled in this study. There were no complete or partial responses. 41.4% of patients achieved stable disease as a best response. Median overall survival was 6.8 months, with a 1-year survival rate of 22%, and median progression-free survival was 2.1 months. The combination produced few grade 3 and no grade 4 toxicities. No grade 3 toxicity occurred in more than 10% of patients. CONCLUSIONS: Although capecitabine and lapatinib is well tolerated, it is not an effective regimen in patients with refractory colorectal adenocarcinoma.
Turkish Journal of Surgery · 2016 · 3 citations · open access
Effect of intraperitoneal cetuximab administration on colonic anastomosis and early postoperative adhesion formation in a rat model
AbstractOBJECTIVE: We aimed to evaluate the effect of intraperitoneal cetuximab administration on the healing of anastomosis and development of early adhesion formation in a rat model. MATERIALS AND METHODS: Twenty-four female rats were used. A colon segment was resected and end-to-end anastomosis was performed. The rats were randomized into three groups after the performance of colonic anastomosis and received 10 mL of intraperitoneal solution including study drugs after closure of abdominal cavity: normal saline was administered to the normal saline group (n=8), cetuximab (400 mg/m(2)) was administered to the postoperative 1 group (n=8) 1 day after surgery, and cetuximab (400 mg/m(2)) was administered to the peroperative group (n=8) during surgery. RESULTS: The mean adhesion grade was 2.63±0.92, and 0.50±0.76 and 0.63±0.74 for control and test groups, respectively. Cetuximab reduced adhesion formation in test groups (p<0.05). When all groups were compared, it was found that vascular endothelial growth factor levels decreased significantly only in the abdomen (p<0.05). Hydroxyproline levels and anastomosis bursting pressure were examined, and a statistical difference was found between groups (hydroxyproline p<0.05, bursting pressure p<0.05). However, when postoperative 1 day group was compared with the control group, it was found that there was no difference between groups according to these parameters (p>0.05), but when peroperative group was compared with the control group a significant decrease was observed in both parameters. Histopathological healing score was also evaluated. No statistical difference between groups was found. CONCLUSION: Twenty-four hours later from the operation, intraperitoneal cetuximab therapy may be a safe and feasible treatment for metastatic colorectal patients.
Phase II study to evaluate the efficacy of capecitabine combined with bevacizumab as first-line treatment in elderly patients with advanced or metastatic colorectal adenocarcinoma
Abstract4119 Background: Colorectal adenocarcinoma is the most common cancer in subjects over 70 years old. New therapies have been developed but limited data about their activity are available in elderly population. Results obtained with capecitabine have shown an appropriate safety and efficacy profile in these patients. The aim of the present study is to evaluate the overall response rate in that patient's population who presents colorectal adenocarcinoma and are treated with the combination of capecitabine+BVZ. Methods: This is a multicentric, non-controlled, open label, phase II clinical trial. Capecitabine(1250mg/m 2 bid, orally)+BVZ(7.5mg/kg, intravenously) treatment was administered in 3-week length cycles until disease progression. Capecitabine dose was reduced to 1000mg/m 2 when the creatinine clearance was between 30 and 50ml/min. Results: A total of 59 patients were included (57.6%, male). Mean age was 76±4.1 years. ECOG status was 0–1 in 96.5 % of the patients. Activities of daily living: moderate to severe dependence and functional incapacity in 24.5% and 5.6% of the patients by Lawton and Barthel scales, respectively. Comorbidities: hypertension (61%), venous thrombosis (5.1%), cardiac disease (5.1%) and acute cerebrovascular accident history (3.4%). Metastases were detected in liver (84.7%), lung (45.8%), local/regional (18.6%) and other locations (5.1%). Mean number of cycles of capecitabine+BVZ was 6.8±6.1. Most frequent grade 3–4 toxicities observed were hand-foot-syndrome (18.6%), diarrhea (8.5%), deep venous thrombosis (6.8%), pain (5.1%) and mucositis (3.4%). Four patients died due to toxicity (mucositis, digestive hemorrhage, hematological toxicity and sepsis, respectively). Metastasis resection was performed in 10.2% of the patients. Treatment response was: 33.3% partial response and 59.0% stable disease. Median progression-free survival was 10.8 months. Conclusions: The combination capecitabine+BVZ in elderly patients appears to have a manageable safety profile and achieves promising results in terms of response rates and progression free-survival. No significant financial relationships to disclose.
Colorectal Cancer · 2024 · 1 citations · open access
Investigation on the cost–effectiveness of Cetuximab in treatment of colorectal cancer: a systematic review
AbstractAim: Assess the cost–effectiveness of cetuximab, utilized as a monotherapy and in combination with other chemotherapy agents, for the treatment of different types of metastatic colorectal cancer (mCRC).Materials & methods: A systematic literature review of recent studies on the cost effectiveness of cetuximab.Results: The review highlights cetuximab's potential to enhance progression-free survival in mCRC, though its broader clinical effectiveness is subject to ongoing debate. However, its cost–effectiveness compared with bevacizumab or standard chemotherapy regimens like FOLFIRI or FOLFOX remains contested.Conclusion: There are discrepancies in the perceived value of anti-EGFR agents like cetuximab concerning overall survival, quality-adjusted life years and progression-free survival vis-à-vis their costs. Subsequent research should focus on balancing these clinical advantages against the financial implications.
DOAJ (DOAJ: Directory of Open Access Journals) · 2015 · 0 citations · open access
CLINICAL EXPERIENCE OF COMBINED AVASTIN THERAPY IN METASTATIC COLORECTAL CANCER
AbstractTreatment of patients with metastatic colorectal cancer (mCRC) is one of the priority questions in oncology. Despite the significant progress in chemotherapy treatment, development of target agents is the only way of further improvement of the results. Bevacizumab (Avastin) is the first biologic demonstrated it’s efficacy in 1st and 2nd therapy lines in mCRC patients and what’s more important – in continuation with first two serial chemotherapy lines.Author presents his own experience of prolonged bevacizumab (Avastin) therapy in several serial therapy lines in mCRC patient.
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.
