ArticleScience translational medicine2016
Anti-VEGF therapy induces ECM remodeling and mechanical barriers to therapy in colorectal cancer liver metastases.
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.
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
165 citing papers in PubMed, 244 citations in OpenAlex.
- Neutralizing dentin sialophosphoprotein facilitates tumor vascular normalization in colorectal cancer by blocking the crosstalk between tumor cells and endothelial cells.Acta pharmaceutica Sinica. B · 2026Article
- Chinese Medicine in Colorectal Cancer Treatment: From Potential Targets and Mechanisms to Clinical Application.Chinese journal of integrative medicine · 2026Review
- Rethinking residual p53 function in HPV-positive cervical cancer cells.Journal of virology · 2026Article
- Mechanobiology of solid tumor vasculature: implications for tumor progression.Cancer metastasis reviews · 2026Review
- Spliceosome induction is a druggable dependency of RAS-driven senescence and cancer.Nature communications · 2026Article
- LPCAT1 depletion inhibits colorectal cancer tumorigenesis and is associated with the ECM-receptor-interaction signaling pathway.Scientific reports · 2026Article
- Interpreting tissue stiffening with lung tumorigenesis by imaging architectural resembling of extracellular matrix components.Communications biology · 2026Article
- DNA methylation-mediated silencing of MEOX1 promotes glycolysis and immune evasion in colorectal cancer cells through inhibition of GLP2R transcription.Cell & bioscience · 2026Article
- Emerging nano-immunotherapeutic strategies achieve metastatic colorectal cancer precision therapy.Journal of nanobiotechnology · 2026Review
- From immune desert to hot tumor: the tripartite synergy of tumor microenvironment-exosomes-immunogenic cell death in pioneering solutions.Frontiers in immunology · 2026Review
- Anlotinib Combined with Programmed Death-1/Programmed Death-Ligand 1 Inhibitor 9 Hydrochloride Suppresses Colorectal Cancer Progression by Inducing Neovascularization and Reprogramming the Tumor Immune Microenvironment in MSS Murine Model.ImmunoTargets and therapy · 2026Article
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- Unravelling theTheranostics · 2026Article
- Colorectal cancer liver metastasis: immunosuppressive microenvironment, signaling pathways, and emerging therapeutic strategies.Frontiers in immunology · 2026Review
- Tumor-associated endothelial cells in tumor immune escape and immunotherapy: multifaceted roles and treatment approaches.Biomarker research · 2025Review
- Constructing anoikis-related signatures in glioma and identifying PLAU as a new prognostic biomarker.BMC medical genomics · 2025Article
- Unveiling the role of the extracellular matrix in the osteosarcoma tumor microenvironment through integrated transcriptomics and experimental validation.Cancer gene therapy · 2025Article
- Integrated single-cell, spatial, and bulk transcriptomics reveal a chromatin regulator-TME prognostic framework guiding precision therapy in cervical cancer.Journal of translational medicine · 2025Article
- Drug resistant glioblastoma stem cells exhibit enriched stemness signatures and share extracellular matrix overexpression.BMC cancer · 2025Article
- Probing the physical hallmarks of cancer.Nature methods · 2025Review
105 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
22 authors at 3 institutions in 1 country.
Funding
Abstract
The survival benefit of anti-vascular endothelial growth factor (VEGF) therapy in metastatic colorectal cancer (mCRC) patients is limited to a few months because of acquired resistance. We show that anti-VEGF therapy induced remodeling of the extracellular matrix with subsequent alteration of the physical properties of colorectal liver metastases. Preoperative treatment with bevacizumab in patients with colorectal liver metastases increased hyaluronic acid (HA) deposition within the tumors. Moreover, in two syngeneic mouse models of CRC metastasis in the liver, we show that anti-VEGF therapy markedly increased the expression of HA and sulfated glycosaminoglycans (sGAGs), without significantly changing collagen deposition. The density of these matrix components correlated with increased tumor stiffness after anti-VEGF therapy. Treatment-induced tumor hypoxia appeared to be the driving force for the remodeling of the extracellular matrix. In preclinical models, we show that enzymatic depletion of HA partially rescued the compromised perfusion in liver mCRCs after anti-VEGF therapy and prolonged survival in combination with anti-VEGF therapy and chemotherapy. These findings suggest that extracellular matrix components such as HA could be a potential therapeutic target for reducing physical barriers to systemic treatments in patients with mCRC who receive anti-VEGF therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.