ArticleCell2020
Senescence-Induced Vascular Remodeling Creates Therapeutic Vulnerabilities in Pancreas Cancer.
Erratum issuedOpen access · bronzeAbstract 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. An erratum has been issued. Cited by 272 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
272citing papers in PubMed, 2 pooled it
17.8field-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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
272 citing papers in PubMed, 2 syntheses or guidelines pooled it, 402 citations in OpenAlex.
- Diabetes Driven Oncogenesis and Anticancer Potential of Repurposed Antidiabetic Drug: A Systemic Review.Cell biochemistry and biophysics · 2024Pooled it
- Can Radiotherapy Empower the Host Immune System to Counterattack Neoplastic Cells? A Systematic Review on Tumor Microenvironment Radiomodulation.Current oncology (Toronto, Ont.) · 2022Pooled it
- Senescence-directed nanotherapy ameliorates fibrosis and overcomes immune exclusion in cancer.Science (New York, N.Y.) · 2026Article
- A Full Spectrum Fibroblast Profiling Panel Reveals Phenotypic and Metabolic Heterogeneity of Cancer-Associated Fibroblasts at the Single-Cell Level.bioRxiv : the preprint server for biology · 2026Article
- Biofabrication and artificial intelligence strategies for investigating solid- and fluid-pressure mechanobiology in pancreatic ductal adenocarcinoma.Cancer metastasis reviews · 2026Review
- Evolutionarily Conserved Epigenetic Regulation of Transcriptional Cell States During Vertebrate Pancreatic Tumorigenesis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Immune surveillance and immune evasion of senescent cells.Nature reviews. Immunology · 2026Review
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- Oncogene inactivation-induced senescence facilitates tumor relapse.Nature communications · 2026Article
- Single-cell and bulk transcriptomics identify senescence-related EMT transcriptional programs and a prognostic framework in pancreatic ductal adenocarcinoma.BMC gastroenterology · 2026Article
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Article
- Immunosenescence in systemic and multi-organ aging: mechanisms, inter-organ crosstalk, and translational opportunities.npj aging · 2026Review
- Multiplexed cytokine and antigen mRNA administration generates durable anti-tumor immunity against pancreatic cancer.Nature communications · 2026Article
- Prognostic significance of therapy-induced senescence and SASP dynamics in acute myeloid leukemia: a retrospective cohort study.BMC cancer · 2026Article
- Glutamine-dependent changes in fibroblast-derived extracellular matrix dictate cancer cell behavior.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- The Aging Microenvironment Shapes Angiogenic Remodeling in IBD-Associated Colorectal Carcinogenesis.Aging cell · 2026Review
- Deprivation of EGFR signal causes senolysis in PDAC with CDK4/6 inhibition.Cell death and differentiation · 2026Article
- Article
- Integrin β3 Promotes Retinal Neovascularization via Endoplasmic Reticulum Stress-Mediated Endothelial Cell Senescence.Investigative ophthalmology & visual science · 2026Article
212 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issued
Authors and funding
20 authors at 5 institutions in 1 country.
Marcus RuscettiDepartment of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
John P MorrisDepartment of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Riccardo MezzadraDepartment of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
James RussellDepartment of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Josef LeiboldDepartment of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Paul B RomesserDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Janelle SimonDepartment of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Amanda KulickDepartment of Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Yu-Jui HoDepartment of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Myles FennellDepartment of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jinyang LiPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Robert J NorgardPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
John E WilkinsonDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Direna Alonso-CurbeloDepartment of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ramya SridharanDepartment of Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
Daniel A HellerDepartment of Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
Elisa de StanchinaDepartment of Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ben Z StangerPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Charles J SherrDepartment of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Scott W LoweDepartment of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: lowes@mskcc.org.
Memorial Sloan Kettering Cancer Center · USUniversity of Pennsylvania · USCornell University · USSt. Jude Children's Research Hospital · USUniversity of Michigan–Ann Arbor · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MVIRAL TRANSACTIVATIONP01CA013106 · NCI · COLD SPRING HARBOR LABORATORY · PI William Richard McCombie · 1985 to 2026
$116.8MThe Role of Focal Oncogene Amplifications in Lung CancerP01CA129243 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Piro Lito · 2007 to 2026
$31.2MCANCER PHARMACOLOGYT32CA062948 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LORRAINE J GUDAS · 1994 to 2026
$12.1MMSKCC Pilot Center for Precision Disease ModelingU54OD020355 · OD · SLOAN-KETTERING INST CAN RESEARCH · PI LOWE, SCOTT W., SOLIT, DAVID B. · 2015 to 2019
$9.9MMSK Paul Calabresi Career Development Award for Clinical OncologyK12CA184746 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Omar Abdel-Wahab, Simon N. Powell · 2015 to 2026
$8.3MMolecular Determinants and Therapeutic Consequences of Immune Heterogeneity in CancerR01CA229803 · NCI · UNIVERSITY OF PENNSYLVANIA · PI STANGER, BEN Z · 2018 to 2022
$3.7MP-selectin-Mediated Targeting of PI3K Nanomedicines to the Tumor MicroenvironmentR01CA215719 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI HELLER, DANIEL ALAN · 2018 to 2022
$3.1MImaging drug uptake and distribution in chemoradiation therapy of pancreatic cancerR01CA194321 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI HUMM, JOHN L, PILLARSETTY, NAGAVARAKISHORE · 2016 to 2019
$2.7MSenescence-Associated Secretory Phenotype (SASP) modulation of the tumor microenvironment as a therapeutic strategy for KRAS-driven tumorsK99CA241110 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI RUSCETTI, MARCUS A. · 2019 to 2019
$137kImproving targeted therapy in KRAS mutant lung cancersF31CA232665 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI SRIDHARAN, RAMYA · 2019 to 2020
$91kHoward Hughes Medical InstituteNCI NIH HHS F31 CA232665NCI NIH HHS K12 CA184746NCI NIH HHS K99 CA241110NCI NIH HHS P01 CA013106NCI NIH HHS P01 CA129243NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA194321NCI NIH HHS R01 CA215719NCI NIH HHS R01 CA229803NCI NIH HHS T32 CA062948NIH HHS U54 OD020355
Abstract
KRAS mutant pancreatic ductal adenocarcinoma (PDAC) is characterized by a desmoplastic response that promotes hypovascularity, immunosuppression, and resistance to chemo- and immunotherapies. We show that a combination of MEK and CDK4/6 inhibitors that target KRAS-directed oncogenic signaling can suppress PDAC proliferation through induction of retinoblastoma (RB) protein-mediated senescence. In preclinical mouse models of PDAC, this senescence-inducing therapy produces a senescence-associated secretory phenotype (SASP) that includes pro-angiogenic factors that promote tumor vascularization, which in turn enhances drug delivery and efficacy of cytotoxic gemcitabine chemotherapy. In addition, SASP-mediated endothelial cell activation stimulates the accumulation of CD8
Indexed as
AgingAnimalsCarcinoma, Pancreatic DuctalCD8-Positive T-LymphocytesCell Line, TumorCell ProliferationCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Gene Expression Regulation, NeoplasticGenes, rasHumansImmunotherapyMAP Kinase Signaling SystemMicePancreatic NeoplasmsRetinoblastoma ProteinCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Retinoblastoma Proteinchemotherapy resistanceendothelial cell activationimmunotherapypancreatic cancersenescencesenescence-associated secretory phenotypetargeted therapyT cellstumor microenvironmentvascular biology
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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.