ArticleCancer research2021
Induction of ADAM10 by Radiation Therapy Drives Fibrosis, Resistance, and Epithelial-to-Mesenchyal Transition in Pancreatic Cancer.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Evaluation of translational potential of mRNA vaccine candidate antigens for pancreatic cancer: a systematic review based on clinical evidence and stratified prioritization strategies.Frontiers in immunology · 2026Pooled it
- Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.Cancer cell international · 2026Review
- Chronic inflammation promotes gastric cancer progression via ADAM10-mediated cleavage of CX3CL1.Scientific reports · 2026Article
- CCR2Frontiers in pharmacology · 2026Article
- Combining advanced radiotherapy techniques and immunotherapy: immunomodulatory mechanisms and clinical prospects.Frontiers in immunology · 2026Review
- ADAM10 Knockout from Human Glioblastoma and Colon Cancer Cells Modulates Diverse Signalling Networks and Inhibits Tumour Growth In Vivo.International journal of molecular sciences · 2025Article
- The pericardium forms as a distinct structure during heart formation.Nature communications · 2025Article
- Dextromethorphan Enhances Apoptosis and Suppresses EMT in PANC-1 Pancreatic Cancer Cells: Synergistic Effects with Gemcitabine.International journal of molecular sciences · 2025Article
- ADAM Proteases in Cancer: Biological Roles, Therapeutic Challenges, and Emerging Opportunities.Cancers · 2025Review
- Role of radiotherapy in surgical approaches to pancreatic cancer treatment: A narrative review.Annals of gastroenterological surgery · 2025Review
- Efficacy of Neoadjuvant Radiotherapy After Chemotherapy and the Optimal Interval from Radiotherapy to Surgery for Borderline Resectable and Resectable Pancreatic Cancer.Annals of surgical oncology · 2025Article
- Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects.Journal of biomedical science · 2025Review
- Sensory nerve EP4 facilitates heterotopic ossification by regulating angiogenesis-coupled bone formation.Journal of orthopaedic translation · 2024Article
- Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Review
- Targeting the pancreatic tumor microenvironment by plant-derived products and their nanoformulations.Medical oncology (Northwood, London, England) · 2024Review
- The preclinical gap in pancreatic cancer and radiotherapy.Disease models & mechanisms · 2024Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Development of a [89Zr]Zr-labeled Human Antibody using a Novel Phage-displayed Human scFv Library.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Targeted irradiation in an autochthonous mouse model of pancreatic cancer.Disease models & mechanisms · 2024Article
- Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma.Nature medicine · 2024Observational
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35 authors at 7 institutions in 2 countries.
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Abstract
Stromal fibrosis activates prosurvival and proepithelial-to-mesenchymal transition (EMT) pathways in pancreatic ductal adenocarcinoma (PDAC). In patient tumors treated with neoadjuvant stereotactic body radiation therapy (SBRT), we found upregulation of fibrosis, extracellular matrix (ECM), and EMT gene signatures, which can drive therapeutic resistance and tumor invasion. Molecular, functional, and translational analysis identified two cell-surface proteins, a disintegrin and metalloprotease 10 (ADAM10) and ephrinB2, as drivers of fibrosis and tumor progression after radiation therapy (RT). RT resulted in increased ADAM10 expression in tumor cells, leading to cleavage of ephrinB2, which was also detected in plasma. Pharmacologic or genetic targeting of ADAM10 decreased RT-induced fibrosis and tissue tension, tumor cell migration, and invasion, sensitizing orthotopic tumors to radiation killing and prolonging mouse survival. Inhibition of ADAM10 and genetic ablation of ephrinB2 in fibroblasts reduced the metastatic potential of tumor cells after RT. Stimulation of tumor cells with ephrinB2 FC protein reversed the reduction in tumor cell invasion with ADAM10 ablation. These findings represent a model of PDAC adaptation that explains resistance and metastasis after RT and identifies a targetable pathway to enhance RT efficacy. SIGNIFICANCE: Targeting a previously unidentified adaptive resistance mechanism to radiation therapy in PDAC tumors in combination with radiation therapy could increase survival of the 40% of PDAC patients with locally advanced disease.
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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.