ArticleOncogene2017
VEGF-ablation therapy reduces drug delivery and therapeutic response in ECM-dense tumors.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 52 citations in OpenAlex.
- Recent advances in interstitial fluid dynamics for diagnostic, targeted drug delivery and precision medicine applications.Drug delivery and translational research · 2026Review
- Overcoming tumour resistance in cancer immunotherapy through predictive and pharmacodynamic biomarkers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Efficacy of pembrolizumab in combination with bevacizumab and oral metronomic cyclophosphamide in the treatment of platinum resistant recurrent ovarian cancer: a retrospective observational study.Gynecologic oncology reports · 2025Article
- Pericytes Modulate Third-Generation Tyrosine Kinase Inhibitor Sensitivity in EGFR-Mutated Lung Cancer Cells Through IL32-β5-Integrin Paracrine Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Normalization of Snai1-mediated vessel dysfunction increases drug response in cancer.Oncogene · 2024Article
- TME-Related Biomimetic Strategies Against Cancer.International journal of nanomedicine · 2024Review
- Time-Dependent Changes in Risk of Progression During Use of Bevacizumab for Ovarian Cancer.JAMA network open · 2023Article
- Nanoparticle-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation.Nature communications · 2023Article
- Image-based modeling of vascular organization to evaluate anti-angiogenic therapy.Biology direct · 2023Article
- Progression after discontinuation of bevacizumab in the first-line treatment of ovarian cancer.Annals of translational medicine · 2023Article
- Hypoxia-induced cancer cell reprogramming: a review on how cancer stem cells arise.Frontiers in oncology · 2023Review
- Host-directed therapies in pulmonary tuberculosis: Updates on anti-inflammatory drugs.Frontiers in medicine · 2022Review
- Harnessing Extracellular Matrix Biology for Tumor Drug Delivery.Journal of personalized medicine · 2021Review
- Tumor dormancy in bone.Cancer reports (Hoboken, N.J.) · 2020Review
- A "Missile-Detonation" Strategy to Precisely Supply and Efficiently Amplify Cerenkov Radiation Energy for Cancer Theranostics.Advanced materials (Deerfield Beach, Fla.) · 2019Article
- Differential Effects of Ang-2/VEGF-A Inhibiting Antibodies in Combination with Radio- or Chemotherapy in Glioma.Cancers · 2019Article
- Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy.Frontiers in molecular biosciences · 2019Review
- Restriction of drug transport by the tumor environment.Histochemistry and cell biology · 2018Review
- LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy.Oncogene · 2018Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inadequate transport of drugs into the tumor tissue caused by its abnormal vasculature is a major obstacle to the treatment of cancer. Anti-vascular endothelial growth factor (anti-VEGF) drugs can cause phenotypic alteration and maturation of the tumor's vasculature. However, whether this consistently improves delivery and subsequent response to therapy is still controversial. Clinical results indicate that not all patients benefit from antiangiogenic treatment, necessitating the development of criteria to predict the effect of these agents in individual tumors. We demonstrate that, in anti-VEGF-refractory murine tumors, vascular changes after VEGF ablation result in reduced delivery leading to therapeutic failure. In these tumors, the impaired response after anti-VEGF treatment is directly linked to strong deposition of fibrillar extracellular matrix (ECM) components and high expression of lysyl oxidases. The resulting condensed, highly crosslinked ECM impeded drug permeation, protecting tumor cells from exposure to small-molecule drugs. The reduced vascular density after anti-VEGF treatment further decreased delivery in these tumors, an effect not compensated by the improved vessel quality. Pharmacological inhibition of lysyl oxidases improved drug delivery in various tumor models and reversed the negative effect of VEGF ablation on drug delivery and therapeutic response in anti-VEGF-resistant tumors. In conclusion, the vascular changes after anti-VEGF therapy can have a context-dependent negative impact on overall therapeutic efficacy. A determining factor is the tumor ECM, which strongly influences the effect of anti-VEGF therapy. Our results reveal the prospect to revert a possible negative effect and to potentiate responsiveness to antiangiogenic therapy by concomitantly targeting ECM-modifying enzymes.
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