ArticleOncogene2019
MAPKAPK2 (MK2) inhibition mediates radiation-induced inflammatory cytokine production and tumor growth in head and neck squamous cell carcinoma.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06416436 (Immunotherapy in Combination With Ablative Radiosurgery to Ultra-high DoSes), which is not on this map. Cited by 24 papers.
What it found
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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.
Immunotherapy in Combination With Ablative Radiosurgery to Ultra-high DoSes (ICARUS): A Phase I Dose-escalation Radiosurgery Study in Metastatic Cancers
Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- DDX21 Enhances Radiosensitivity in Head and Neck Squamous Cell Carcinoma by Suppressing MK2-Mediated DNA Damage Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A novel framework for the discovery of MAPK-activated protein kinase 2 (MAPKAPK2) inhibitors using a multi-feature deep learning ensemble.Journal of computer-aided molecular design · 2026Article
- Targeting p38α in cancer: challenges, opportunities, and emerging strategies.Molecular oncology · 2026Review
- Molecular Docking and Target-Specific Binding Profiles of Benzosuberane-Based Compounds.ChemMedChem · 2025Review
- MK2 promotes p16 negative head and neck cancer migration, invasion, and metastasis.Cancer letters · 2025Article
- AZU1 as a DNA Methylation-Driven Gene: Promoting Oxidative Stress in High-Altitude Pulmonary Edema.Antioxidants (Basel, Switzerland) · 2025Article
- Radiation-induced esophagitis and lung injury during esophageal squamous cell cancer therapy is correlated to tumor gene expression phenotype.Toxicology research · 2025Article
- Inhibition of p38-MK2 pathway enhances the efficacy of microtubule inhibitors in breast cancer cells.eLife · 2025Article
- Inhibition of p38-MK2 pathway enhances the efficacy of microtubule inhibitors in breast cancer cells.bioRxiv : the preprint server for biology · 2025Article
- Targeting radiotherapy-induced inflammation in cancer metastasis: insights into immune modulation, therapeutic opportunities and radiogenomics.Frontiers in oncology · 2025Review
- MK2-mediated AKT/MYC signaling activation promotes epithelial-mesenchymal transition in lung adenocarcinoma.Frontiers in genetics · 2025Article
- Loss of MK2 Enhances Radiation-Mediated Apoptosis in Bladder Cancer.World journal of oncology · 2024Article
- Article
- MAPK-activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in glioma.Frontiers in oncology · 2024Article
- GINS2 promotes the progression of human HNSCC by altering RRM2 expression.Cancer biomarkers : section A of Disease markers · 2024Article
- Musashi-2 Deficiency Triggers Colorectal Cancer Ferroptosis by Downregulating the MAPK Signaling Cascade to Inhibit HSPB1 Phosphorylation.Biological procedures online · 2023Article
- Tumor MK2 transcript levels are associated with improved response to chemotherapy and patient survival in non-small cell lung cancer.Physiological genomics · 2023Article
- P38 MAPK and Radiotherapy: Foes or Friends?Cancers · 2023Review
- MK2 drives progression of pancreas and colon cancers by suppressing CD8Frontiers in immunology · 2023Article
- Diagnostics of HNSCC Patients: An Analysis of Cell Lines and Patient-Derived Xenograft Models for Personalized Therapeutical Medicine.Diagnostics (Basel, Switzerland) · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Radiation therapy (RT) is a cornerstone of treatment in the management of head and neck squamous cell carcinomas (HNSCC), yet treatment failure and disease recurrence are common. The p38/MK2 pathway is activated in response to cellular stressors, including radiation, and promotes tumor inflammation in a variety of cancers. We investigated MK2 pathway activation in HNSCC and the interaction of MK2 and RT in vitro and in vivo. We used a combination of an oropharyngeal SCC tissue microarray, HNSCC cell lines, and patient-derived xenograft (PDX) tumor models to study the effect of RT on MK2 pathway activation and to determine how inhibition of MK2 by pharmacologic (PF-3644022) and genetic (siRNA) methods impacts tumor growth. We show that high phosphorylated MK2 (p-MK2) levels are associated with worsened disease-specific survival in p16-negative HNSCC patients. RT increased p-MK2 in both p16-positive, HPV-positive and p16-negative, HPV-negative HNSCC cell lines. Pharmacologic inhibition or gene silencing of MK2 in vitro abrogated RT-induced increases in p-MK2; inflammatory cytokine expression and expression of the downstream MK2 target, heat shock protein 27 (HSP27); and markers of epithelial-to-mesenchymal transition. Mouse PDX models treated with a combination of RT and MK2 inhibitor experienced decreased tumor growth and increased survival. Our results suggest that MK2 is a potential prognostic biomarker for head and neck cancer and that MK2 pathway activation can mediate radiation resistance in HNSCC.
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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.