ArticleOncotarget2014
Targeting hypoxia-inducible factor-1α (HIF-1α) in combination with antiangiogenic therapy: a phase I trial of bortezomib plus bevacizumab.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Interaction of HIF-1a with various cell death pathways in tumor immune microenvironment (TIME).Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Article
- Exploring the efficacy of a novel cannabidiol and bevacizumab combination in non-small cell lung cancer.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Article
- Hypoxic microenvironment in cancer: role in metabolic reprogramming.Frontiers in oncology · 2026Review
- Targeting the proteasome in cancer therapy: development and future opportunities in natural products.Frontiers in pharmacology · 2026Review
- Epithelial‑mesenchymal plasticity and cisplatin resistance in germ cell tumors: Mechanisms and emerging therapeutic strategies (Review).International journal of oncology · 2025Review
- Review
- Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer.Cellular & molecular biology letters · 2025Review
- Review
- Inspiring Tactics with the Improvement of Mitophagy and Redox Balance for the Development of Innovative Treatment against Polycystic Kidney Disease.Biomolecules · 2024Review
- PBRM1-deficient PBAF complexes target aberrant genomic loci to activate the NF-κB pathway in clear cell renal cell carcinoma.Nature cell biology · 2023Article
- Article
- Targeted therapy for head and neck squamous cell carcinoma microenvironment.Frontiers in medicine · 2023Review
- Targeting hypoxia in solid and haematological malignancies.Journal of experimental & clinical cancer research : CR · 2022Review
- Targeting hypoxia-inducible factors for breast cancer therapy: A narrative review.Frontiers in pharmacology · 2022Review
- Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells.Scientific reports · 2021Article
- An Overview of the Recent Development of Anticancer Agents Targeting the HIF-1 Transcription Factor.Cancers · 2021Review
- HIF-1α Metabolic Pathways in Human Cancer.Advances in experimental medicine and biology · 2021Review
- Potential Therapeutic Strategies for Lung and Breast Cancers through Understanding the Anti-Angiogenesis Resistance Mechanisms.International journal of molecular sciences · 2020Review
- Dynamic contrast-enhanced perfusion parameters in ovarian cancer: Good accuracy in identifying high HIF-1α expression.PloS one · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
purposeWe hypothesized that bortezomib, an agent that suppresses HIF-1α transcriptional activity, when combined with bevacizumab, would obviate the HIF-1α resistance pathway. The objectives of this phase I trial were to assess safety and biological activity of this combination. EXPERIMENTAL
designPatients with advanced, refractory malignancies were eligible. Patients received bevacizumab and bortezomib (3-week cycle) with dose expansions permitted if responses were seen and for assessing correlates. Pharmacodynamic assessment included plasma VEGF, VEGFR2, 20S proteasome inhibition, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and HIF-1α tumor expression.
resultsNinety-one patients were treated (median=6 prior treatments). The FDA-approved doses of both drugs were safely reached, and the recommended phase 2 dose (RP2D) is bevacizumab 15 mg/kg with bortezomib 1.3 mg/m(2). Four patients attained partial response (PR) and seven patients achieved stable disease (SD) ≥ 6 months (Total SD ≥ 6 months/PR=11 (12%)). The most common drug-related toxicities included thrombocytopenia (23%) and fatigue (19%). DCE-MRI analysis demonstrated no dose-dependent decreases in K(trans) although analysis was limited by small sample size (N=12).
conclusionCombination bevacizumab and bortezomib is well-tolerated and has demonstrated clinical activity in patients with previously treated advanced malignancy. Pharmacodynamic assessment suggests that inhibition of angiogenic activity was achieved.
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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.