ArticleAging cell2019
Targeting amphiregulin (AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand (PD-L1)-mediated immunosuppression.
Article in Aging cell, 2019. 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 91 papers, 5 of them syntheses that pooled it.
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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.
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Who cites it
91 citing papers in PubMed, 5 syntheses or guidelines pooled it, 135 citations in OpenAlex.
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment.International journal of molecular sciences · 2021Pooled it
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1.International journal of molecular sciences · 2021Pooled it
- Pooled it
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models).International journal of molecular sciences · 2021Pooled it
- Pooled it
- Identifying the therapeutic effects of talniflumate in metastatic papillary thyroid microcarcinoma through integrating multiple omics analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Amphiregulin drives EGFR-dependent genome stability in colorectal cancer and represents a targetable vulnerability.Oncogene · 2026Article
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- Breaking senescence restriction: MAFK-AREG axis promotes NSCLC cells to resist doxorubicin.Oncology letters · 2026Article
- Immunological consequences of senescence in physiology and pathology.Journal of translational medicine · 2026Review
- Senescent endothelial cell-derived extracellular vesicles promote neoadjuvant chemoresistance in colorectal cancer via GPX4.Communications biology · 2026Article
- Multi-Transcriptomic Analysis Reveals That EREG-Driven TME Crosstalk Defines Anti-EGFR Response in Colorectal Cancer.Cancer medicine · 2026Article
- Prognostic alternative splicing signatures in esophageal cancer reveal SF3A3 as a key oncogenic splicing factor.Translational cancer research · 2026Article
- The natural flavonoid dihydromyricetin targets senescent cells via PRDX2 and alleviates age-related diseases.Nature communications · 2026Article
- HOXD13-mediated immune crosstalk between cancer cells and tumor-associated macrophages drives colorectal cancer progression.Journal for immunotherapy of cancer · 2026Article
- Glucocorticoid Receptor Activation Reprograms NK Cells to Drive AREG-Mediated Immunosuppression: A Pan-Cancer Role for AREG.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dynamic dual regulation of amphiregulin in liver pathophysiology: balancing regeneration and disease progression via the EGFR axis.Frontiers in medicine · 2026Review
- The controversial role of senescence-associated secretory phenotype (SASP) in cancer therapy.Molecular cancer · 2025Review
- Spatiotemporal multi-omics analysis uncovers NAD-dependent immunosuppressive niche triggering early gastric cancer.Signal transduction and targeted therapy · 2025Article
- Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 9 institutions in 3 countries.
Funding
Abstract
Aging is characterized by a progressive loss of physiological integrity, while cancer represents one of the primary pathological factors that severely threaten human lifespan and healthspan. In clinical oncology, drug resistance limits the efficacy of most anticancer treatments, and identification of major mechanisms remains a key to solve this challenging issue. Here, we highlight the multifaceted senescence-associated secretory phenotype (SASP), which comprises numerous soluble factors including amphiregulin (AREG). Production of AREG is triggered by DNA damage to stromal cells, which passively enter senescence in the tumor microenvironment (TME), a process that remarkably enhances cancer malignancy including acquired resistance mediated by EGFR. Furthermore, paracrine AREG induces programmed cell death 1 ligand (PD-L1) expression in recipient cancer cells and creates an immunosuppressive TME via immune checkpoint activation against cytotoxic lymphocytes. Targeting AREG not only minimized chemoresistance of cancer cells, but also restored immunocompetency when combined with classical chemotherapy in humanized animals. Our study underscores the potential of in vivo SASP in driving the TME-mediated drug resistance and shaping an immunosuppressive niche, and provides the proof of principle of targeting major SASP factors to improve therapeutic outcome in cancer medicine, the success of which can substantially reduce aging-related morbidity and mortality.
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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.