ArticleCancer cell2020
CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer.
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Article in Cancer cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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137citing papers in PubMed
13.1field-weighted citation impact, top 1% of its field
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Who cites it
137 citing papers in PubMed, 219 citations in OpenAlex.
- Integrated multi-omics analysis reveals the molecular landscape and therapeutic strategies in Chinese cervical cancer patients.PLoS biology · 2026Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- Pharmacological inhibition of CDK7 and CDK9 suppresses gastrointestinal (colon) cancer progression through modulation of stemness, epithelial-mesenchymal transition, and chemoresistance.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A Versatile Multiplexed Immunofluorescence Strategy for Efficient, Host-Independent, and Scalable Spatial Protein Profiling.Small methods · 2026Article
- Inhibition of ADSS2-mediated de novo AMP biosynthesis re-sensitizes acute myeloid leukemia to BH3 mimetics.Nature cancer · 2026Article
- Inhibition of RNA polymerase II-activating CDK9 and CDK12/13, but not of cell cycle relevant CDKs, induces apoptosis by downregulating the short-lived Bcl-2 proteins Mcl1 and Bfl1/A1.Cell death & disease · 2026Article
- ZNF274 constrains lineage plasticity and drives intrinsic resistance to CDK7 inhibitors in pancreatic cancer.Nature communications · 2026Article
- Transcription Factor Subtype Governs Response and Resistance to DLL3-Directed T-Cell Engagement in Small Cell Lung Cancer.bioRxiv : the preprint server for biology · 2026Article
- The roles of cell cycle proteins in regulating the tumor immune microenvironment.Genes & diseases · 2026Review
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- MYC at the tumor-immune interface: mechanisms of immune escape and immunotherapy resistance.Frontiers in immunology · 2026Review
- The Role of CDKs in the Regulation of the Monocyte/Macrophage Immune Response.Current medicinal chemistry · 2026Review
- Identification of RPGRIP1L as an instability-maintaining gene to drive tumor growth and PD-L1 expression via Hedgehog signaling in breast cancer.BMC cancer · 2025Article
- The Dual Effects of CDK4/6 Inhibitors on Tumor Immunity.Cancers · 2025Review
- Tumour Cell Size Control and Its Impact on Tumour Cell Function.Cell proliferation · 2025Review
- Advancing small cell lung cancer metastasis research: innovations in preclinical mouse models.Cancer metastasis reviews · 2025Review
- CDK12 regulates cellular metabolism to promote glioblastoma growth.JCI insight · 2025Article
- CDK7-targeted therapy effectively disrupts cell cycle progression and oncogenic signaling in head and neck cancer.Signal transduction and targeted therapy · 2025Article
77 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
49 authors at 8 institutions in 2 countries.
Hua ZhangLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address: hua.zhang@nyulangone.org.
Camilla L ChristensenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Ruben DriesDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Matthew G OserDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jiehui DengLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Brian DiskinS. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, NY 10016, USA.
Fei LiLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Yuanwang PanLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Xuzhu ZhangDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Yandong YinDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Eleni PapadopoulosLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Val PyonLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Cassandra ThakurdinLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Nicholas KwiatkowskiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Kandarp JaniDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Alexandra R RabinLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Dayanne M CastroDepartments of Biology and Computer Science, Center for Genomics and Systems Biology, New York University, New York, NY 10010, USA.
Ting ChenLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Heather SilverLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Qingyuan HuangLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Mirna BulatovicLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Catríona M DowlingLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Belen SundbergS. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, NY 10016, USA.
Alan LeggettDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Michela RanieriLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Han HanLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Shuai LiLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Annan YangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Kristen E LabbeLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Christina AlmonteLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Vladislav O SviderskiyDepartment of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Max QuinnLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Jack DonaghueLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Eric S WangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Tinghu ZhangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Zhixiang HeDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Vamsidhar VelchetiLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Peter S HammermanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Gordon J FreemanDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Richard BonneauDepartments of Biology and Computer Science, Center for Genomics and Systems Biology, New York University, New York, NY 10010, USA.
William G KaelinDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Kate D SutherlandCancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
Ariena KersbergenCancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Andrew J AguirreDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Guo-Cheng YuanDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Eli RothenbergDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
George MillerS. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, NY 10016, USA.
Nathanael S GrayDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA. Electronic address: nathanael_gray@dfci.harvard.edu.
Kwok-Kin WongLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address: kwok_kin.wong@nyulangone.org.
NYU Langone Health · USDana-Farber Cancer Institute · USNew York University · USBrigham and Women's Hospital · USBroad Institute · USHarvard University · USThe University of Melbourne · AUWalter and Eliza Hall Institute of Medical Research · AU
Funding
VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI A. Heather Eliassen · 1985 to 2026
$330.6MVaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1MTR&D 4: Revealing Microstructure: Biophysical modeling and validation for discovery and clinical careP41EB017183 · NIBIB · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Hersh Chandarana · 2014 to 2026
$19.3MStructureP01CA154303 · NCI · DANA-FARBER CANCER INST · PI ECK, MICHAEL J · 2012 to 2021
$17.8MThe von Hippel-Lindau Tumor Suppressor Gene and Kidney Cancer: Insights into Oxygen Sensing and Treating Cancers Caused by Undruggable MutationsR35CA210068 · NCI · DANA-FARBER CANCER INST · PI WILLIAM G. KAELIN · 2016 to 2026
$10.8MMUC1-C Oncoprotein Evades Immune Destruction in Non-small Cell Lung CancerR01CA166480 · NCI · DANA-FARBER CANCER INST · PI KUFE, DONALD W., WONG, KWOK KIN · 2012 to 2021
$6.3MTargeting the transcriptional and epigenetic landscape in chemo-refractory Small-Cell Lung CancerU01CA213333 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI GRAY, NATHANAEL SCHIANDER, WONG, KWOK KIN · 2017 to 2021
$3.3MNew Therapeutic Targets in Small Cell Lung Cancer that are Epistatic or Synthetic Lethal with pRB LossK08CA222657 · NCI · DANA-FARBER CANCER INST · PI OSER, MATTHEW GILBERT · 2017 to 2021
$886kFunctional interrogation of epigenetic vulnerabilities in KRAS-mutant pancreatic cancerK08CA218420 · NCI · DANA-FARBER CANCER INST · PI AGUIRRE, ANDREW JAMES · 2017 to 2021
$886kInvestigation and targeting of the transcriptional and epigenetic landscape of Small Cell Lung CancerK99CA201618 · NCI · DANA-FARBER CANCER INST · PI CHRISTENSEN, CAMILLA L · 2016 to 2017
$257kNCI NIH HHS K08 CA218420NCI NIH HHS K08 CA222657NCI NIH HHS K99 CA201618NCI NIH HHS P01 CA154303NCI NIH HHS P30 CA006516NCI NIH HHS P30 CA016087NCI NIH HHS R01 CA166480NCI NIH HHS R35 CA210068NCI NIH HHS U01 CA213333NIBIB NIH HHS P41 EB017183
Abstract
Cyclin-dependent kinase 7 (CDK7) is a central regulator of the cell cycle and gene transcription. However, little is known about its impact on genomic instability and cancer immunity. Using a selective CDK7 inhibitor, YKL-5-124, we demonstrated that CDK7 inhibition predominately disrupts cell-cycle progression and induces DNA replication stress and genome instability in small cell lung cancer (SCLC) while simultaneously triggering immune-response signaling. These tumor-intrinsic events provoke a robust immune surveillance program elicited by T cells, which is further enhanced by the addition of immune-checkpoint blockade. Combining YKL-5-124 with anti-PD-1 offers significant survival benefit in multiple highly aggressive murine models of SCLC, providing a rationale for new combination regimens consisting of CDK7 inhibitors and immunotherapies.
Indexed as
Genomic InstabilityAnimalsAntineoplastic AgentsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesChemokine CXCL9Cyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesDNA DamageFemaleHumansImmune SystemInflammationInterferon-gammaLung NeoplasmsMaleAntineoplastic AgentsChemokine CXCL9CXCL9 protein, humanCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesIFNG protein, humanInterferon-gammaPDCD1 protein, humanProgrammed Cell Death 1 ReceptorPyrazolesPyrrolesTumor Necrosis Factor-alphaYKL-5-124anti-tumor immunityCDK7cell cyclegenome instabilityimmune checkpoint blockadeimmunotherapyreplication stresssingle-cell analysissmall cell lung cancerYKL-5-124
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