ArticleScience (New York, N.Y.)2014
Spatial and temporal diversity in genomic instability processes defines lung cancer evolution.
Article in Science (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05189171 (MicroOrganoSphere Drug Screen to Lead Care), which is not on this map. Cited by 667 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
MicroOrganoSphere Drug Screen to Lead Care (MODEL) Precision Oncology Pilot Trial in Colorectal Cancer (CRC)
Who cites it
667 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,155 citations in OpenAlex.
- Identification of Novel Multi-Omics Expression Landscapes and Meta-Analysis of Landscape-Based Competitive Endogenous RNA Networks in ALDH+ Lung Adenocarcinoma Stem Cells.BioMed research international · 2022Pooled it
- Phase IB/II study of alpelisib combined with paclitaxel in patients with PIK3CA-altered metastatic or recurrent gastric cancer.The oncologist · 2026Trial
- Spatial multi-omics revealed the impact of tumor ecosystem heterogeneity on immunotherapy efficacy in patients with advanced non-small cell lung cancer treated with bispecific antibody.Journal for immunotherapy of cancer · 2023Trial
- Inferring gene expression profiles of tumor clones.Bioinformatics (Oxford, England) · 2026Article
- Review
- Molecular Residual Disease in Non-Small Cell Lung Cancer: Technology or Patient Outcomes?Journal of personalized medicine · 2026Review
- Lung tumour secretome and extracellular vesicles: mechanisms, biomarkers, and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- Spatiotemporal heterogeneity in non-small cell lung cancer: A paradigm shift from characterization to dynamic management (Review).Oncology letters · 2026Review
- Clinical overall survival prediction and disease characteristics of locally advanced non-small cell lung cancer: an integrated analysis based on the SEER and TCGA databases.Translational cancer research · 2026Article
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Article
- Motif-Centered Analyses Reveal Universal and Tissue-Specific Mutagenic Mechanisms Operating in the Human Body.bioRxiv : the preprint server for biology · 2026Article
- Integrating machine learning and single-cell sequencing to reveal the role of kinase-related genes in subtype classification and prognostic significance of lung squamous cell carcinoma.Discover oncology · 2026Article
- Genetic barcoding uncovers the clonal makeup of solid and liquid biopsies and their ability to capture intra-tumoral heterogeneity.Molecular systems biology · 2026Article
- Article
- The prognostic value of intra- and peritumoral habitat analysis in nasopharyngeal carcinoma: combining IVIM and ASL.European radiology · 2026Article
- Article
- Innovative approaches for lung cancer screening and interception.Nature reviews. Clinical oncology · 2026Review
- Delineation of the heterogeneity underlying genomic instability in hereditary breast cancers reveals four disease subtypes.Experimental & molecular medicine · 2026Article
607 more citing papers are in PubMed but not listed here.
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Authors and funding
43 authors at 10 institutions in 5 countries.
Funding
Abstract
Spatial and temporal dissection of the genomic changes occurring during the evolution of human non-small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity. Despite maintained carcinogen exposure, tumors from smokers showed a relative decrease in smoking-related mutations over time, accompanied by an increase in APOBEC-associated mutations. In tumors from former smokers, genome-doubling occurred within a smoking-signature context before subclonal diversification, which suggested that a long period of tumor latency had preceded clinical detection. The regionally separated driver mutations, coupled with the relentless and heterogeneous nature of the genome instability processes, are likely to confound treatment success in NSCLC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.