ArticleCell2020
Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing.
Registry-linked trialOpen access · hybridAbstract read
In one paragraph
Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06399926 (A Open-label, Random, Multi-central Prospective Cohort of Observation Study on the Efficacy and Safety of Intraventricule Pemetrexed Disodium Via Ommaya Reservoir), which is not on this map. Cited by 464 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
464citing papers in PubMed, 1 pooled it
33.9field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Open-label, Random, Multi-central Prospective Cohort of Observation Study on the Efficacy and Safety of Intraventricule Pemetrexed Disodium Via Ommaya Reservoir
Who cites it
464 citing papers in PubMed, 1 synthesis or guideline pooled it, 677 citations in OpenAlex.
- Advances and frontiers in pulmonary fibrosis and lung cancer research (2000-2024): a bibliometric analysis.Frontiers in medicine · 2025Pooled it
- Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Advancing the understanding of the immune escape in lung cancer immunotherapy: Global trends, collaborations, and future directions.Human vaccines & immunotherapeutics · 2026Article
- Lung Cancer Patients Display Increased Expression of Bovine Meat and Milk Factor (BMMF) Proteins in Peritumor Alveolar Macrophages.International journal of cancer · 2026Article
- Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026Review
- Interpretable scRNA-seq Analysis with Intelligent Gene Selection.Applied biochemistry and biotechnology · 2026Article
- Clinical metastatic cancer from initiation to colonization: emerging challenges and breakthroughs.Oncogene · 2026Review
- Lineage identity governs oncogene dependence in mouse NSCLC models of KRAS inhibitor resistance.Nature genetics · 2026Article
- Loss of lineage fidelity underpins drug resistance in Kras-mutant lung cancer.Nature genetics · 2026Article
- PDLIM2 in lung adenocarcinoma metastasis.Neoplasia (New York, N.Y.) · 2026Article
- STEAP2 Is a Candidate Marker of a 7q/CNA-Associated Iron-Handling Malignant Epithelial State in Lung Adenocarcinoma.Cancers · 2026Article
- Dissecting residual disease in spheroids reveals pan-cancer persistence signatures and a therapeutic window for oncolytic viruses.Molecular therapy. Oncology · 2026Article
- DRIVE: a comprehensive resource deciphering drug-induced transcriptomic and splicing response in cancer cell.Neoplasia (New York, N.Y.) · 2026Article
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Lung tumour secretome and extracellular vesicles: mechanisms, biomarkers, and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Early EGFR Inhibition Triggers Actionable Tumor and Microenvironmental Remodeling in Lung Cancer.Cancer research communications · 2026Article
- AXL phosphosite mapping links FAK1 and YAP1 signaling to erlotinib resistance in EGFR-mutant lung cancer.Cell reports · 2026Article
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Statescope: an integrative deconvolution framework for discovering cell states in tumors.Nature communications · 2026Article
- The FOSB-IGFBP5-IGF-1 axis: a novel regulatory pathway that suppresses prostate cancer growth.Cancer gene therapy · 2026Article
404 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
43 authors at 7 institutions in 1 country.
Ashley MaynardChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Caroline E McCoachDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Julia K RotowLowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Lincoln HarrisChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Franziska HaderkDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
D Lucas KerrDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Elizabeth A YuDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Erin L SchenkDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Weilun TanChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Alexander ZeeChan Zuckerberg Biohub, San Francisco, CA 94158, USA; Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Michelle TanChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Philippe GuiDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Tasha LeaHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Wei WuDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Anatoly UrismanDepartment of Pathology University of California, San Francisco, San Francisco, CA 94143, USA.
Kirk JonesDepartment of Pathology University of California, San Francisco, San Francisco, CA 94143, USA.
Rene SitChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Pallav K KolliDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94143 USA.
Eric SeeleyDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Yaron GesthalterDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Daniel D LeChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Kevin A YamauchiChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
David M NaegerDenver Health Medical Center, Denver, CO 80204, USA; Department of Radiology, University of Colorado, Aurora, CO 80045, USA.
Sourav BandyopadhyayHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Khyati ShahDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Lauren CechDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Nicholas J ThomasDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Anshal GuptaDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Mayra GonzalezDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Hien DoDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Lisa TanDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Bianca BacaltosDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Rafael Gomez-SjobergChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Matthew GubensDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Thierry JahanDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Johannes R KratzDepartment of Surgery, University of California, San Francisco, CA 94143, USA.
David JablonsDepartment of Surgery, University of California, San Francisco, CA 94143, USA.
Norma NeffChan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Robert C DoebeleDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Jonathan WeissmanDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
Collin M BlakelyDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: collin.blakely@ucsf.edu.
Spyros DarmanisChan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: spyros.darmanis@czbiohub.org.
Trever G BivonaDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: trever.bivona@ucsf.edu.
University of California, San Francisco · USChan Zuckerberg Initiative (United States) · USUniversity of Colorado Anschutz Medical Campus · USDana-Farber Cancer Institute · USHoward Hughes Medical Institute · USUniversity of California, Santa Cruz · USUniversity of Colorado Hospital · US
Funding
MUTIDISCIPLINARY TRAINING PROGRAM IN LUNG DISEASEST32HL007185 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI David J Erle, LAURENCE HUANG · 1985 to 2026
$24.6MPaul Calabresis Award in Clinical Oncology ResearchK12CA086913 · NCI · UNIVERSITY OF COLORADO DENVER · PI VIRGINIA F. BORGES, Jill E Slansky · 2000 to 2026
$17.8MUCSF Project 1U54CA224081 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CALVIN J KUO · 2017 to 2026
$12.9MThe Cancer Target Discovery and Development Network at UCSFU01CA217882 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BANDYOPADHYAY, SOURAV, BIVONA, TREVER G · 2017 to 2021
$5.2MCharacterization of YAP as a rational companion target in lung cancerR01CA204302 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trever G Bivona · 2017 to 2026
$3.7MRational Combined Inhibition of NF-kB and EGFR to Optimize Lung Cancer TreatmentR01CA169338 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G · 2013 to 2023
$3.4MGenomics and Functional Characterization of NF1-mutated Lung CancerR01CA227807 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLISSON, ERIC · 2018 to 2022
$2.8M(PQ7) Defining a new mode of RAS signaling in cancer from cytoplasmic protein granulesR01CA231300 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G, HUANG, BO · 2019 to 2023
$2.3MOptimizing biologically-based rational polytherapy in ALK+ lung cancerR01CA211052 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G · 2017 to 2021
$1.8MDoris Duke Charitable Foundation 2018110NCI NIH HHS K12 CA086913NCI NIH HHS R01 CA169338NCI NIH HHS R01 CA204302NCI NIH HHS R01 CA211052NCI NIH HHS R01 CA227807NCI NIH HHS R01 CA231300NCI NIH HHS U01 CA217882NCI NIH HHS U54 CA224081NHLBI NIH HHS T32 HL007185
Abstract
Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.
Indexed as
Biomarkers, TumorCell LineEcosystemHumansLung NeoplasmsMacrophagesSequence Analysis, RNASingle-Cell AnalysisT-LymphocytesTumor MicroenvironmentBiomarkers, TumorALKEGFRlung cancersingle-cell RNA sequencingtargeted therapy
Identifiers
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Read underepoch 390
Registered trials
NCT06399926ClinicalTrials.gov
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.