DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for small cell lung 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 moduleSmall cell lung 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
Structures already discussed alongside 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
Structure of L1196M Mutant Anaplastic Lymphoma Kinase — Crizotinib has a real, experimentally solved structure in complex with this target (PDB 2YFX, 1.7 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.
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helix sheet vghdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2YFX · 1.7 Å · ligand Crizotinib (VGH). Experimental structure, not a prediction.
What the evidence adds up to
Small cell lung cancer incidence has declined over the past 30 years, but the disease remains frustrating to research and treat. Numerous attempts to enhance the anti-tumour effects of traditional chemotherapy have not been successful. Most patients relapse quickly after first-line therapy, and overall 5-year survival is about 5%. Despite dramatic initial responses to chemotherapy, progress in systemic therapy over the last 20 years has been painfully slow.
Combining standard regimens with newer agents has doubled median survival in some recent trials, according to a 2001 review. However, since the 1980s, clinical research into chemotherapy, biological agents, and molecular targeting agents has still failed to produce a consensus on appropriate maintenance therapy. The 2015 review states that a substantial lack of agreement remains regarding the therapeutic management of maintenance therapy for small cell lung cancer.
Genomic alterations in small cell lung cancer have emerged as potential targets for therapeutic intervention, and novel targeted agents hold the promise of increasing survival with manageable toxicity. However, the 2017 overview of targeted therapy for lung cancer discusses only drugs approved for non-small cell lung cancer, not small cell. No targeted therapy has yet been established for small cell lung cancer based on the abstracts provided.
What is still missing is a validated targeted therapy for this specific disease, along with consensus on maintenance therapy trial design. Patient stratification based on the genomic alterations described remains preclinical. Funding for trials that move beyond standard chemotherapy combinations into mechanism-based approaches is needed.
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.).
Cellular and molecular biology of small cell lung cancer: an overview.
AbstractAlthough the incidence of small cell lung cancer (SCLC) has declined during the past 30 years, it remains a frustrating disease to research and treat. Numerous attempts to enhance the anti-tumor effects of traditional chemotherapy for SCLC have not been successful. For any tumor to become cancerous, various genetic mutations and biologic alterations must occur in the cell that, when combined, render it a malignant neoplasm. New and novel therapies based on understanding these mechanisms of transformation are needed. Herein we provide an in-depth view of some of the genomic alterations in SCLC that have emerged as potential targets for therapeutic intervention.
[Clinical Efficacy of Crizotinib in Advanced ALK Positive Non-small Cell Lung Cancer].
AbstractBACKGROUND: The aim of this study is to explore clinical efficacy of crizotinib in advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer. METHODS: patients with advanced non-small cell lung cancer habouring ALK positive were randomly divided into crizotinib group (n=14) and chemotherapy group (n=14). Patients in the crizotinib group were receive oral treatment with crizotinib (250 mg) twice daily. Patients in the chemotherapy group were administrated docetaxel injection (75 mg/m2) every three weeks and every patient was treated at least 3 period. Then clinical efficacy was observed after 12 mo followed-up. RESULTS: Effective rate of patients in the crizotinib group was 64.29%. It was significantly higher than that of the chemotherapy group (21.43%)(P=0.026). The stable rate of patients in the crizotinib group was 85.71%. It was significantly higher than that of the chemotherapy group 40.86% (χ2=5.600, P=0.018). Median progression free survival (PFS) of the crizotinib group was 7.0 mo. It was longer than that of the chemotherapy group (4.0 mo)(P=0.002). CONCLUSIONS: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced ALK positive non-small cell lung cancer. The median PFS of patients is shorter. It can improve the quality of life about patients. .
Expert Review of Anticancer Therapy · 2001 · 4 citations
Advances in systemic therapy of small cell cancer of the lung
AbstractOver the last 20 years, progress in the therapy of small cell lung cancer has been painfully slow. Despite dramatic initial responses to chemotherapy, most patients relapse quickly with an overall 5-year survival of about 5%. Recent trials however offer some hope at changing this picture. Combining standard regimens with newer agents has doubled median survival in some cases. The use of novel targeted agents holds the promise of significantly increasing the survival in this disease, with manageable toxicity. This review outlines current treatment strategies, summarizes recent clinical trials and offers a view of what the next 5 years may hold for the treatment of small cell lung cancer.
[Research Progression of Maintenance Therapy in Small Cell Lung Cancer].
AbstractLung cancer is one of the common malignant tumors in the world, the incidence of small cell lung cancer is about 15% among them. Small cell lung cancer is highly sensitive to first-line chemotherapy, but most of the patients relapse after the first-line therapy quickly. Despitemany clinical researchof chemotherapy, biological agents and molecular targeting agents since the 1980s, there still remains a substantial lack of consensus regarding the appropriate therapeutic management on maintenance therapy of small cell lung cancer. The review focuses on maintenance therapy of small cell lung cancer.
Journal of Pulmonology and Respiratory Research · 2017 · 0 citations · open access
A decade of targeted therapy for non-small cell lung cancer
AbstractChemotherapy is one of the main treatment options for cancer. However, chemotherapeutic agents usually suffer from poor pharmaceutical properties that restrict their use. Targeted therapy drugs have been developed to specifically target changes in cancer cells that help these cells to grow. Such drugs often work when standard chemotherapeutic drugs do not, they often have less severe side effects and they are most often used for advanced cancers. The objective of this article is to give an overview about the 16 FDA-approved targeted therapy drugs to treat non-small cell lung cancer.
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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