DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for squamous 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 moduleSquamous 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 squamous 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
From 1985 to 1995, 713,043 primary lung malignancies were recorded in the National Cancer Data Base. The overall ten-year relative survival rate for all lung cancer patients was 7%. For stage I non-small cell lung cancer patients who had surgery, five-year survival exceeded 50% across all histologic groups. The authors concluded that overall survival remained poor and that a continuing need for improved prevention and treatment measures existed.
Squamous cell lung cancer causes roughly 400,000 deaths worldwide per year. A comprehensive genomic characterisation of 178 cases found that squamous cell lung cancer is characterised by a broader and more complex group of genomic alterations than adenocarcinoma. Potentially targetable genes or pathways exist, but meaningful therapeutic gains based on the molecular pathobiology of squamous cell lung cancer had not yet been realised as of 2013. Advanced squamous cell lung cancer had enjoyed little of the recent progress benefiting adenocarcinoma patients.
The 2014 review noted that advanced squamous cell lung cancer had begun to see some change, but the underlying molecular pathology remained complex. No new targeted agents were approved for this indication at that time. A 2016 paper on relapsed small-cell lung cancer reported that median survival for relapsed disease was about five to six months even with best available therapy, and that topotecan was the only FDA-approved agent for that setting.
What is still missing is a large-scale, prospective trial that can stratify squamous cell lung cancer patients by the specific genomic alterations found in their tumours, and the funding and collaboration between industry, government, cooperative groups, and academic institutions needed to translate those findings into patient benefit.
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.).
Ten-year survey of lung cancer treatment and survival in hospitals in the United States
AbstractBACKGROUND: Primary lung cancer accounts for approximately 14% of all new cancers and 28% of cancer deaths in the U.S. Previous reviews have shown limited progress in the management or outcome of this devastating disease. METHODS: Reports described in the current study were 713,043 primary lung malignancies diagnosed between 1985 and 1995 and submitted to the National Cancer Data Base. Demographic, tumor, and treatment patterns for 1995 were compared with those for 1985-1987, 1988-1991, and 1992-1994. Ten-year relative survival rates were presented for selected demographic and histologic groups and 5-year relative survival rates were presented by stage and dominant treatment modalities for major carcinoma histologies. RESULTS: Previously observed demographic trends were evident, with increasing proportions of patients being older, female, and African American, and more cases reported to be adenocarcinomas. There was a substantial shift toward more complete staging but no change in the distribution of staged cases. Compared with earlier patients, fewer 1995 patients received cancer-directed treatment. More surgical patients underwent lymph node dissection, and radiation treatment was supplemented more often with chemotherapy. The overall 10-year relative survival rate was 7%. The 5-year survival for American Joint Committee on Cancer Stage I surgical patients was >50% for all nonsmall cell histologic groups. CONCLUSIONS: Recent shifts in treatment, although minimal, are consistent with current literature concerning the effectiveness of lung carcinoma treatment. The authors believe that the overall poor survival of lung carcinoma patients points to a continuing need for improved prevention and treatment measures. The comparatively superior survival of Stage I nonsmall cell lung carcinoma surgical patients indicates that a substantial number of patients have the potential to be treated successfully.
Frontiers in Oncology · 2013 · 17 citations · open access
Targeting Genomic Alterations in Squamous Cell Lung Cancer
AbstractSquamous cell lung cancer causes approximately 400,000 deaths worldwide per year. Identification of specific molecular alterations, such as activating mutations in the epidermal growth factor receptor kinase and echinoderm microtubule-associated protein-like 4/anaplastic lymphoma kinase fusions have led to significant therapeutic gains in patients with adenocarcinoma. However, meaningful therapeutic gains based on the molecular pathobiology of squamous cell lung cancer have not yet been realized. A comprehensive genomic characterization of 178 cases of squamous cell lung cancer has recently been reported. Squamous cell lung cancer appears to be characterized by a broader and more complex group of genomic alterations than adenocarcinoma. In this review, potentially targetable genes or pathways in squamous cell lung cancer are emphasized in relation to available therapeutic agents in development or active clinical trials. This organization of data will provide a framework for development for clinical investigation. Squamous cell lung cancer appears to be characterized by not only driver mutations in candidate genes but also gene copy number alterations resulting in tumor proliferation and survival. Better understanding of these genetic alterations and their use as therapeutic targets will require broad collaboration between industry, government, the cooperative groups, and academic institutions with the ultimate goal of rapid translation of scientific advancement to patient benefit.
Frontiers in Oncology · 2014 · 5 citations · open access
Promising Targets and Current Clinical Trials in Metastatic Squamous Cell Lung Cancer
AbstractSquamous cancer of the lung (SQCC), although no longer the premier variant of non-small cell lung cancer, continues to impose a heavy world-wide burden. Advanced SQCC has enjoyed little of the recent progress benefiting patients with adenocarcinoma of the lung, but that has now begun to change. This article reviews the underlying molecular pathology of SQCC, as well as potential new targets and the corresponding novel targeted agents; included are some of which may soon be approvable in this notoriously hard-to-treat indication.
Translational Cancer Research · 2016 · 4 citations · open access
Cisplatin, etoposide, and irinotecan for relapsed small-cell lung cancer
AbstractSmall-cell lung cancer (SCLC) is one of the most chemosensitive solid tumors. Unfortunately, a majority of patients will experience relapse of their disease within 1 year of completing treatment. Median survival for patients with relapsed disease is dismal at about 5–6 months even with best available therapy. Good performance status and sensitivity to first-line chemotherapy are significant prognostic factors of survival in patients treated for relapsed SCLC (1). Therapy options for relapsed SCLC remain limited, due to poor efficacy of most chemotherapy regimens and the poor performance status of many of these patients at relapse. Currently, topotecan is the only FDA-approved agent for the treatment of relapsed SCLC based on a phase III trial that demonstrated improvement in survival and quality of life (QOL) compared to best supportive care (2).
Food Science and Technology · 2021 · 1 citations · open access
Efficacy of pembrolizumab combined with anlotinib in 3 patients with advanced non-small cell lung cancer
AbstractNon-small-cell lung carcinoma (NSCLC) is any type of epithelial lung cancer and accounts for about 85% of all lung cancers. Pembrolizumab, a PD-1 inhibitor, is approved to treat patients with advanced NSCLC. Anlotinib, a multi-target tyrosine kinase inhibitor, is approved in China for treating patients with advanced NSCLC with progression or recurrence after ≥ 2 lines of systemic chemotherapy. Whether pembrolizumab combined with anlotinib has synergistic effects on treating advanced NSCLC patients remains unclear. Here we reported that three cases of patients with advanced NSCLC had a good response and a long time of PR to pembrolizumab combined with anlotinib treatment, indicating that combined administration of pembrolizumab and anlotinib can be optional management for advanced NSCLC.
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.
