DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for non-small cell lung 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 moduleNon-small cell lung 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
Structures already discussed alongside non-small cell lung carcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 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 b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
In a phase 3 open-label trial, 347 patients with advanced ALK-positive non-small cell lung cancer who had received one prior platinum-based regimen were randomly assigned to crizotinib 250 mg twice daily or intravenous chemotherapy (pemetrexed or docetaxel every 3 weeks). Median progression-free survival was 7.7 months with crizotinib versus 3.0 months with chemotherapy (hazard ratio 0.49, 95% CI 0.37 to 0.64, P<0.001). Response rates were 65% (95% CI 58 to 72) for crizotinib and 20% (95% CI 14 to 26) for chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib (hazard ratio for death 1.02, 95% CI 0.68 to 1.54, P=0.54). Common adverse events with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels; patients reported greater reductions in lung cancer symptoms and greater improvement in global quality of life with crizotinib than with chemotherapy.
A 2010 case series from China reported 24 patients with refractory non-small cell lung cancer who received sunitinib at 37.5 mg orally once daily, either as a single agent (20 patients) or in combination with pemetrexed, gemcitabine, or gefitinib (4 patients). Eight patients achieved a confirmed objective response, a response rate of 33.3% (8/24). Seven patients had stable disease, giving a disease control rate of 62.5% (15/24). Nine patients had progressive disease. Median progression-free survival was 4 months, with a range of 4 to 18 weeks. Grade 3-4 adverse events included fatigue/asthenia (45.8%, 11/24), hand-foot syndrome (29.1%, 7/24), and dry skin (25%, 5/24). The authors concluded that sunitinib showed substantial activity but called for high-quality prospective studies.
A 2023 review summarises drug repurposing approaches for non-small cell lung carcinoma, noting that median five-year survival for metastatic disease remains approximately 3% and that the disease exhibits high rates of treatment resistance driven by heterogeneity and cancer stem cell plasticity. The review lists candidate repurposed drug classes including antihypertensives, anti-hyperlipidemics, anti-inflammatory drugs, anti-diabetics, and anti-microbials, but provides no new clinical trial data.
What is still missing are prospective, randomised trials for repurposed agents in non-small cell lung cancer, adequate funding for such trials, and patient stratification strategies that might identify which subgroups, if any, derive meaningful benefit from drugs like sunitinib or other repurposed candidates. The crizotinib data, while positive for progression-free survival and response rate in a molecularly defined subgroup, did not show an overall survival benefit at interim analysis.
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 · 2013 · 3411 citations · open access
Crizotinib versus Chemotherapy in Advanced <i>ALK</i> -Positive Lung Cancer
AbstractBACKGROUND: In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. METHODS: We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. RESULTS: The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy. CONCLUSIONS: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.).
Current Oncology · 2023 · 34 citations · open access
Drug Repurposing in Non-Small Cell Lung Carcinoma: Old Solutions for New Problems
AbstractLung cancer is the second most common cancer and the leading cause of cancer-related deaths in 2022. The majority (80%) of lung cancer cases belong to the non-small cell lung carcinoma (NSCLC) subtype. Despite the increased screening efforts, the median five-year survival of metastatic NSCLC remains low at approximately 3%. Common treatment approaches for NSCLC include surgery, multimodal chemotherapy, and concurrent radio and chemotherapy. NSCLC exhibits high rates of resistance to treatment, driven by its heterogeneity and the plasticity of cancer stem cells (CSCs). Drug repurposing offers a faster and cheaper way to develop new antineoplastic purposes for existing drugs, to help overcome therapy resistance. The decrease in time and funds needed stems from the availability of the pharmacokinetic and pharmacodynamic profiles of the Food and Drug Administration (FDA)-approved drugs to be repurposed. This review provides a synopsis of the drug-repurposing approaches and mechanisms of action of potential candidate drugs used in treating NSCLC, including but not limited to antihypertensives, anti-hyperlipidemics, anti-inflammatory drugs, anti-diabetics, and anti-microbials.
Combination Chemotherapy and Radiotherapy in Smalt-Cell Carcinoma of the Lung
AbstractA combination of chemotherapy (Cytoxan, vincristine, and CCNU) and radiation therapy was used to treat 37 patients with small-cell carcinoma of the lung. There was 49% complete remission and an overall 76% objective response with an overall median survival of 12.5 months and 17 months for those showing a complete response. No serious morbidity was observed.
AbstractLung cancer is the leading cause of cancer deaths for both men and women in the United States. Most patients present with late stages of disease, rendering them incurable. Despite this dismal outcome, there is optimism; modern treatment for lung cancer has been shown to increase survival, improve quality of life, and be cost effective. This article reviews the current treatment strategies for non-small cell lung cancer and small cell lung cancer as well as discusses future treatments, including the exciting biologic agents that are in clinical trials.
Sunitinib in patients with refractory NSCLC: Primary results from China.
Abstracte18145 Background: Sunitinib, a small molecule, is a multitargeted receptor kinase inhibitor which targets the vascular endothelial growth factor receptor and platelet-derived growth factor receptor as well as several others. Several clinical trial results have already demonstrated the therapeutic potential of this agent in renal cell carcinoma and gastrointestinal stromal tumor, however, only few studies were conducted to investigate the effectiveness of the use of sunitinib in refractory NSCLC. We reported a case series of patients with previously treated, refractory non-small cell lung cancer and evaluated the clinical activity and tolerability of sunitinib. Methods: Patients with stage IIIb or IV NSCLC for whom platinum-based chemotherapy had failed received sunitinib at a dose of 37.5 mg orally once daily combination with or without standard agents or regimens currently used in the NSCLC. Results: We illustrated 24 refractory NSCLC patients who received sunitinib treatment. Two patients were treated with pemetrexed besides sunitinib, two other patients were treated sunitinib in combination with gemcitabine and gefitinib respectively. Other 20 patients received sunitinib as a single agent. The starting dose of sunitinib was 37.5 mg/d. eight patients who received sunitinib achieved a confirmed objective response. The response rate was 33.3% (8/24). Seven patients showed stable disease. Disease control rate is 62.5% (15/24). Night patients showed progressive disease. PFS ranged from 4 weeks to 18 weeks. mPFS for this study is 4 moths. 1 year survival rate is still follow up. The most commonly AEs (grade 3-4) included fatigue/asthenia (45.8%, 11/24), dry skin (25%, 5/24), and hand-foot syndrome 29.1% (7/24). Other AEs (grade 3-4) were thrombocytopenia, anemia and diarrhea. Conclusions: Sunitinib, as a single agent or in combination with chemotherapy, was well generally tolerated and showed substantial activity in refractory lung cancer. High-quality prospective studies are needed to be conducted. No significant financial relationships to disclose.
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.
