ReviewFrontiers in immunology2025
"Brake" and "accelerator": revisiting tumor cell direct responses and the paradox of aggression in anti-VEGF therapy.
Review in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed, 1 synthesis or guideline pooled it.
- The efficacy of angiogenesis inhibitors combined with chemotherapy in advanced breast cancer: a systematic review and meta-analysis.Frontiers in oncology · 2026Pooled it
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted anti-angiogenic therapies against vascular endothelial growth factor (VEGF) are standard treatments for various advanced cancers. However, their clinical benefits are often limited by acquired resistance, with some patients even exhibiting paradoxical tumor aggressiveness and accelerated metastasis. Traditional views primarily attribute this to hypoxia-driven mechanisms within the tumor microenvironment. Based on an analysis of receptor tyrosine kinase (RTK) interactions and pathway rewiring within tumor cells, this paper proposes an integrated "brake-accelerator" model. We posit that in the presence of VEGF, VEGFR2-Mesenchymal-Epithelial Transition factor (MET) heterocomplexes and neuropilin (NRP) co-receptors restrict bypass pathway activity. Upon VEGF blockade, this "brake" is released, and bypass "accelerators" are passively or actively amplified, collectively driving invasive transformation and immune evasion. We identify "direct signal remodeling" in tumor cells as a potentially underappreciated contributor. This process acts as a potential upstream integration node that, alongside treatment-induced hypoxic stress and immune-stromal microenvironment remodeling, constitutes a "tripartite stress" framework. Through Darwinian clonal selection and induced phenotypic plasticity, this framework drives the evolution of tumors towards a more aggressive phenotype. This paper systematically reviews the molecular mechanisms supporting this model, including the regulatory role of VEGFR2-MET complexes, the signal hub function of NRP, and the networked characteristics of escape pathways. Finally, we discuss the implications of this conceptual model for future clinical practice, including the development of dynamic biomarkers based on intrinsic tumor cell characteristics and the design of more precise combination and adaptive treatment strategies to overcome resistance to anti-VEGF therapy and improve patient prognosis.
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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.