ArticleCancer cell2021
Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities.
Registry-linked trialAbstract read
In one paragraph
Article in Cancer cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05257551 (Tempus SCLC Observational Study), which is not on this map. Cited by 621 papers, 1 of them a synthesis that pooled it.
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621citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.
Tempus SCLC Observational Study: A Tissue and Longitudinal Circulating Tumor DNA (ctDNA) Biomarker Profiling Study of Patients With Small Cell Lung Cancer (SCLC) Using Comprehensive Next-Generation Sequencing (NGS) Assays
Who cites it
621 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Prognostic values and clinical significance of POU2F3 expression in neuroendocrine carcinomas: a meta-analysis with a focus on small cell lung cancer.Annals of medicine · 2025Pooled it
- DNA hypomethylation identifying clinical benefit subgroup of small-cell lung cancer: multi-omics analysis of a phase II trial with durvalumab plus olaparib as maintenance therapy.Journal for immunotherapy of cancer · 2026Trial
- Trial
- NOTCH1 reverses immune suppression in small cell lung cancer through reactivation of STING.The Journal of clinical investigation · 2025Trial
- Harnessing local and system immune profiling delineating differential responders to first-line sintilimab (anti-PD-1 antibody) combined with chemotherapy in extensive-stage small cell lung cancer: an exploratory biomarker analysis of a phase II study.Signal transduction and targeted therapy · 2025Trial
- High Endothelial Venules in Small Cell Lung Cancer: Prognostic Subtypes and Therapeutic Implications for Immunoradiotherapy.International journal of cancer · 2026Article
- Polycomb scaffolding subunit EED supports the SCLC neuroendocrine identity and EGFR-mutant LUAD-to-SCLC transformation.The Journal of clinical investigation · 2026Article
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- Sensitizing tumor response to topoisomerase I antibody-drug conjugate by selective CDK7 inhibition.Science advances · 2026Article
- Clinicopathological Features of DLL3 Expression and T-Cell Infiltration in LCNEC: Insights From Pathology and Clinical Response to Tarlatamab.Thoracic cancer · 2026Article
- Plasma nucleosome profiling reports on tumor burden and molecular subtypes in small cell lung cancer.The Journal of clinical investigation · 2026Article
- Artificial intelligence and radiomics in small cell lung cancer: a narrative review of imaging and multisource data integration.Journal of thoracic disease · 2026Review
- Article
- PAX5 modulates vascularization and contributes to neuroendocrine lineage transition during carcinoma progression.The Journal of clinical investigation · 2026Article
- Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.Biomarker research · 2026Review
- Review
- Article
- Rechallenge With Immunotherapy for ES-SCLC: Efficacy and Safety From a Retrospective Propensity Score-Matched Study.Cancer medicine · 2026Article
- Pan-cancer analysis and mechanistic insights of tuft cell-like tumors.Genes & diseases · 2026Review
- What's new in neoplastic pulmonary pathology 2026: updates on grading, staging and molecular testing.Journal of pathology and translational medicine · 2026Article
561 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
30 authors.
Carl M GayDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
C Allison StewartDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Elizabeth M ParkDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lixia DiaoDepartment of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sarah M GrovesDepartment of Biochemistry, Vanderbilt University Medical Center, Nashville, TN, USA.
Simon HeekeDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Barzin Y NabetDepartment of Oncology Biomarker Development, Genentech Inc., South San Francisco CA, USA.
Junya FujimotoDepartment of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Luisa M SolisDepartment of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Wei LuDepartment of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yuanxin XiDepartment of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Robert J CardnellDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Qi WangDepartment of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Giulia FabbriAstraZeneca, Waltham, MA, USA.
Kasey R CargillDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Natalie I VokesDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Kavya RamkumarDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bingnan ZhangDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Carminia M Della CorteDepartment of Precision Medicine, Oncology Division, University of Campania "Luigi Vanvitelli", Naples, Italy.
Paul RobsonThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Stephen G SwisherDepartment of Thoracic and Cardiovascular Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jack A RothDepartment of Thoracic and Cardiovascular Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bonnie S GlissonDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
David S ShamesDepartment of Oncology Biomarker Development, Genentech Inc., South San Francisco CA, USA.
Ignacio I WistubaDepartment of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jing WangDepartment of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Vito QuarantaDepartment of Biochemistry, Vanderbilt University Medical Center, Nashville, TN, USA.
John MinnaDepartment of Internal Medicine and Simmons Cancer Center, the University of Texas Southwestern Medical Center, Dallas, TX, USA.
John V HeymachDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lauren Averett ByersDepartment of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: lbyers@mdanderson.org.
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MShared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI William Carl Skarnes · 1985 to 2026
$61.9MUNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI GIBBONS, DON LYNN · 1996 to 2024
$57.4MCoordinating center for the NCI small cell lung cancer research consortiumU24CA213274 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Lauren Averett Byers, JOHN D. MINNA · 2017 to 2026
$12.9MTRAINING FOR ACADEMIC ONCOLOGY/HEMATOLOGYT32CA009666 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Michael Davies, Courtney DiNardo · 1994 to 2026
$9.8MTherapeutic strategies for targeting PARP1 in small cell lung cancerR01CA207295 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Lauren Averett Byers · 2016 to 2026
$3.7MNovel therapeutic approaches for enhancing anti-tumor immunity in SCLCU01CA213273 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BYERS, LAUREN AVERETT, HEYMACH, JOHN V. · 2017 to 2021
$3.0MDeveloping ASCL1 and NeuroD1 lineage oncogene targeted therapy for small cell lung cancerU01CA213338 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MINNA, JOHN D. · 2017 to 2021
$3.0MPhenotype Transitions in Small Cell Lung CancerU01CA215845 · NCI · VANDERBILT UNIVERSITY · PI LOPEZ, CARLOS FEDERICO, QUARANTA, VITO · 2017 to 2021
$2.8MModeling tumor heterogeneity, to develop new therapeutic strategies for treatment of resistant small cell lung cancerR50CA243698 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Catherine Allison Stewart · 2020 to 2026
$701kNCI NIH HHS P30 CA016672NCI NIH HHS P30 CA034196NCI NIH HHS P50 CA070907NCI NIH HHS R01 CA207295NCI NIH HHS R50 CA243698NCI NIH HHS T32 CA009666NCI NIH HHS U01 CA213273NCI NIH HHS U01 CA213338NCI NIH HHS U01 CA215845NCI NIH HHS U24 CA213274
Abstract
Despite molecular and clinical heterogeneity, small cell lung cancer (SCLC) is treated as a single entity with predictably poor results. Using tumor expression data and non-negative matrix factorization, we identify four SCLC subtypes defined largely by differential expression of transcription factors ASCL1, NEUROD1, and POU2F3 or low expression of all three transcription factor signatures accompanied by an Inflamed gene signature (SCLC-A, N, P, and I, respectively). SCLC-I experiences the greatest benefit from the addition of immunotherapy to chemotherapy, while the other subtypes each have distinct vulnerabilities, including to inhibitors of PARP, Aurora kinases, or BCL-2. Cisplatin treatment of SCLC-A patient-derived xenografts induces intratumoral shifts toward SCLC-I, supporting subtype switching as a mechanism of acquired platinum resistance. We propose that matching baseline tumor subtype to therapy, as well as manipulating subtype switching on therapy, may enhance depth and duration of response for SCLC patients.
Indexed as
AnimalsCell Line, TumorCisplatinFemaleGene Expression Regulation, NeoplasticHumansImmunityLung NeoplasmsMiceMice, NudePrognosisSmall Cell Lung CarcinomaTranscription FactorsCisplatinTranscription FactorsASCL1EMTintratumoral heterogeneityNEUROD1neuroendocrinePOU2F3SCLC
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Registered trials
NCT05257551ClinicalTrials.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.