DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for lung adenocarcinoma — screening already-approved drugs against its 49-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLung adenocarcinoma maps to a 49-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
approvedVandetanibApproved drug
Structures already discussed alongside lung adenocarcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of phosphorylated RET tyrosine kinase domain — Vandetanib has a real, experimentally solved structure in complex with this target (PDB 2IVU, 2.5 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 zd6drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2IVU · 2.5 Å · ligand Vandetanib (ZD6). Experimental structure, not a prediction.
What the evidence adds up to
A 2013 deep-sequencing study of primary lung adenocarcinoma tumours and adjacent normal tissue from six Korean female never-smokers identified 47 somatic mutations and 19 fusion transcripts, including a fusion involving the c-RET gene. Gene expression profiles integrated with genomic aberrations pointed to disturbances in G2/M transition and mitotic progression as causally linked to tumorigenesis in these patients, and several novel microRNA-target interactions were proposed as key regulatory elements. The sample size is six, and no survival or response data are reported.
A 2024 retrospective analysis of 471 patients who had surgery for lung adenocarcinoma reported an overall survival rate of 76.23% for the entire cohort. There was no significant difference in survival between patients classified as G1 and G2 tumour grades, and patients with spread through air spaces (STAS) had a lower survival rate than those without STAS. The study does not report median survival, progression-free survival, or any treatment response data.
A 2019 Delphi consensus document from Spain addressed treatment options after immunotherapy for advanced wild-type lung adenocarcinoma. Consensus was reached on 29 of 31 statements in the second round. The panel agreed that a platinum-based chemotherapy should follow first-line immunotherapy without chemotherapy, and that docetaxel plus nintedanib may be appropriate after durvalumab in refractory patients, after progression to first-line chemotherapy plus immunotherapy, or after second-line chemotherapy following first-line immunotherapy. The consensus is based on expert opinion, not on new trial data, and no response rates or survival figures are given.
What is still missing are prospective trials that test the proposed sequencing of treatments after immunotherapy, validated biomarkers to stratify patients beyond PD-L1 expression and tumour mutational burden, and larger genomic studies that link the molecular alterations found in never-smokers to actionable targets and clinical outcomes.
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 · 84 citations · open access
A High-Dimensional, Deep-Sequencing Study of Lung Adenocarcinoma in Female Never-Smokers
AbstractBACKGROUND: Deep sequencing techniques provide a remarkable opportunity for comprehensive understanding of tumorigenesis at the molecular level. As omics studies become popular, integrative approaches need to be developed to move from a simple cataloguing of mutations and changes in gene expression to dissecting the molecular nature of carcinogenesis at the systemic level and understanding the complex networks that lead to cancer development. RESULTS: Here, we describe a high-throughput, multi-dimensional sequencing study of primary lung adenocarcinoma tumors and adjacent normal tissues of six Korean female never-smoker patients. Our data encompass results from exome-seq, RNA-seq, small RNA-seq, and MeDIP-seq. We identified and validated novel genetic aberrations, including 47 somatic mutations and 19 fusion transcripts. One of the fusions involves the c-RET gene, which was recently reported to form fusion genes that may function as drivers of carcinogenesis in lung cancer patients. We also characterized gene expression profiles, which we integrated with genomic aberrations and gene regulations into functional networks. The most prominent gene network module that emerged indicates that disturbances in G2/M transition and mitotic progression are causally linked to tumorigenesis in these patients. Also, results from the analysis strongly suggest that several novel microRNA-target interactions represent key regulatory elements of the gene network. CONCLUSIONS: Our study not only provides an overview of the alterations occurring in lung adenocarcinoma at multiple levels from genome to transcriptome and epigenome, but also offers a model for integrative genomics analysis and proposes potential target pathways for the control of lung adenocarcinoma.
Treatment options beyond immunotherapy in patients with wild-type lung adenocarcinoma: a Delphi consensus
AbstractPURPOSE: Immunotherapy-based approaches are standard first-line treatments for advanced/metastatic lung cancer or for chemoradiotherapy consolidation in locally advanced disease. Uncertainty on how to treat patients at disease progression prompted us to develop a consensus document on post-immunotherapy options in Spain for patients with advanced wild-type lung adenocarcinoma. METHODS: After extensive literature review, a 5-member scientific committee generated 33 statements in 4 domains: general aspects (n = 4); post-durvalumab in locally advanced disease (n = 6); post-first-line immunotherapy ± chemotherapy in advanced/metastatic disease (n = 11); and post-first-line platinum-based chemotherapy in advanced/metastatic disease (n = 12). A panel of 26 lung cancer experts completed 2 Delphi iterations through an online platform rating their degree of agreement/disagreement (first-round scale 1-5 and second-round scale 1-4, 1 = strongly disagree, 4/5 = strongly agree) for each statement. Second-round consensus: ≥ 70% of responses were in categories 1/2 (disagreement) or 3/4 (agreement). RESULTS: Consensus was reached for 2/33 statements in the first Delphi round and in 29/31 statements in the second round. Important variables informing treatment at disease progression with an immunotherapy-based treatment include: disease aggressiveness, previous treatment, accumulated toxicity, progression-free interval, PD-L1 expression, and tumour mutational burden. A platinum-based chemotherapy should follow a first-line immunotherapy treatment without chemotherapy. Treatment with docetaxel + nintedanib may be appropriate post-durvalumab in refractory patients or following progression to first-line chemotherapy + immunotherapy, or second-line chemotherapy after first-line immunotherapy, or first-line chemotherapy in some patients with low/negative PD-L1 expression, or second-line immunotherapy after first-line chemotherapy. CONCLUSIONS: To support decision making following progression to immunotherapy-based treatment in patients with advanced wild-type lung adenocarcinoma, a consensus document has been developed.
Thoracic Cancer · 2019 · 8 citations · open access
Osimertinib‐induced severe interstitial lung disease: A case report
AbstractLung cancer is globally one of the leading causes of malignant tumor-related mortality and ranks as having the highest incidence found in men and second in women. Osimertinib is a drug used to target lung cancer but its toxicity is not fully understood. Here we present a case of lung adenocarcinoma in a 78-year-old man that was treated and responded favorably with Osimertinib after the failure of other therapies. Unfortunately, the patient developed severe interstitial lung disease during the treatment procedure.
Translational Lung Cancer Research · 2020 · 5 citations · open access
Analysis of the clinical effect of osimertinib on 90 cases with advanced lung adenocarcinoma
AbstractBACKGROUND: Primary or secondary drug resistance of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) is a new challenge in the treatment of advanced non-small cell lung cancer (NSCLC). Osimertinib is a third-generation EGFR-TKI, and its efficacy and safety in NSCLC patients with first-generation EGFR-TKI resistance, especially lung adenocarcinoma, are not yet clear. The purpose of this study was to observe the efficacy and adverse reactions of osimertinib in the treatment of patients with advanced lung adenocarcinoma. METHODS: From January 2017 to December 2018, 90 patients with advanced (stage IV) lung adenocarcinoma were diagnosed in Shanghai Chest Hospital. The disease of these patients (94.4%) progressed after first-line EGFR-TKI treatment, and 43.3% of patients received third-line or beyond third-line treatment. The efficacy and adverse reactions of osimertinib treatment were observed. RESULTS: Among 90 patients with advanced lung adenocarcinoma, 57 (63.3%) achieved partial response (PR), 27 (30.0%) had stable disease (SD), and 6 (6.7%) had progressive disease (PD). The objective response rate (ORR) was 63.3%, and the disease control rate (DCR) was 93.3%. The median progression-free time (mPFS) was 10.41 months (95% CI: 8.91-11.91 months), and the median overall survival (mOS) was 31.37 months (95% CI: 26.37-36.37 months). The incidence of adverse events of degree 3 and above was 7.78%. The main adverse events were diarrhea (28.9%) and rash (24.4%). After symptomatic treatment, the incidence of adverse events was significantly reduced. CONCLUSIONS: Osimertinib has a definite curative effect in the treatment of patients with advanced lung adenocarcinoma, and the incidence of adverse reactions is low.
[Vandetanib treatment in refractory advanced lung adenocarcinoma patients: five cases and review of literature].
AbstractBACKGROUND AND OBJECTIVE: Vandetanib is a once-daily oral multi-target inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET) tyrosine kinases. The current study aimed to evaluate the effect and safety of vandetanib administered in refractory advanced lung adenocarcinoma patients. METHODS: Five patients who accepted chemotherapy and Tarceva therapy as first- and second-line treatments received vandetanib (300 mg, oral, once daily). RESULTS: The effects are stable disease on two patients (40%) and progressive disease on three patients (60%). With a median follow-up of 36 months, one patient remained on follow-up. The median progression free survival (PFS) is 2 months, and the mean overall survival is 22.6 months. The adverse events include rash (n=2), skin change (n=2), paronychia (n=2), asymptomatic QTc prolongation (n=2), ST-T change (n=1), diarrhea (n=1), and increased transaminase (n=1). CONCLUSIONS: There were lower incidences of severe side effects with vandetanib therapy in refractory advanced lung adenocarcinoma patients. The results of effect and safety of vandetanib are similar with the related reviewed articles.
Ten-Year Observational Study of Patients with Lung Adenocarcinoma: Clinical Outcomes, Prognostic Factors, and Five-Year Survival Rates
AbstractBackground/Objectives: Lung carcinoma is the leading cause of cancer-related deaths globally, with lung adenocarcinoma being the most prevalent subtype. This study aims to review the clinical data and survival outcomes of patients diagnosed with lung adenocarcinoma who underwent surgical treatment. Methods: We conducted a retrospective analysis of 471 patients who had surgery for lung adenocarcinoma at our institution. Their medical histories, including previous neoplasms, comorbidities, tumor characteristics, and symptoms, were thoroughly reviewed. We calculated the overall survival rate and evaluated the impact of tumor grading and spread through air spaces (STAS) on patient outcomes. Results: The survival rate for the entire cohort was 76.23%. There was no significant difference in survival rates between patients classified as G1 and G2, suggesting that a simplified two-tier grading system may be more effective. Patients with STAS had a lower survival rate than those without STAS. Conclusions: Our findings indicate that a simplified grading system may improve prognostic evaluations for lung adenocarcinoma patients. Furthermore, STAS is a crucial factor affecting survival rates and should be considered in future treatment strategies. Expanding research in this area is essential to enhance treatment approaches for lung adenocarcinoma patients.
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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