Trial reportCancer chemotherapy and pharmacology2014
Pilot trial of EZN-2968, an antisense oligonucleotide inhibitor of hypoxia-inducible factor-1 alpha (HIF-1α), in patients with refractory solid tumors.
Trial report in Cancer chemotherapy and pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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.
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Who cites it
96 citing papers in PubMed, 152 citations in OpenAlex.
- Combination of the histone deacetylase inhibitor vorinostat with bevacizumab in patients with clear-cell renal cell carcinoma: a multicentre, single-arm phase I/II clinical trial.British journal of cancer · 2017Trial
- Meta-analysis of adverse events in clinical studies with antisense oligonucleotide therapies.Molecular therapy. Nucleic acids · 2026Review
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Advances in antisense oligonucleotide treatment for cancer.Japanese journal of clinical oncology · 2026Review
- Hypoxia-inducible factors link inflammation and lipid metabolism in atherosclerotic macrophages.Frontiers in cardiovascular medicine · 2026Review
- Hypoxic tumor microenvironment and immune cell dynamics: From metabolic reprogramming to therapeutic innovation.Iranian journal of basic medical sciences · 2026Review
- Hypoxia-Inducible Factors in Rheumatoid Arthritis: Central Pathogenic Roles and Therapeutic Opportunities.Journal of inflammation research · 2026Review
- Targeting miR-32-5p suppresses c-MYC-driven proliferation and induces apoptosis in MCF-7 breast cancer cells.Medical oncology (Northwood, London, England) · 2025Article
- Review
- Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery.Transcription · 2025Review
- HIF-1 and HIF-2 in cancer: structure, regulation, and therapeutic prospects.Cellular and molecular life sciences : CMLS · 2025Review
- 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
- Metabolic regulation of myeloid-derived suppressor cells in tumor immune microenvironment: targets and therapeutic strategies.Theranostics · 2025Review
- Identification of Hypoxia-ALCAMAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Modulation of hypoxia-inducible factor-1 signaling pathways in cancer angiogenesis, invasion, and metastasis by natural compounds: a comprehensive and critical review.Cancer metastasis reviews · 2024Review
- Therapeutic Targeting of Hypoxia-Inducible Factors in Cancer.International journal of molecular sciences · 2024Review
- DNA mechanocapsules for programmable piconewton responsive drug delivery.Nature communications · 2024Article
- Myriad factors and pathways influencing tumor radiotherapy resistance.Open life sciences · 2024Review
- Dual hypoxia-responsive supramolecular complex for cancer target therapy.Nature communications · 2023Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
purposeHypoxia-inducible factor-1 (HIF-1) facilitates the adaptation of normal and tumor tissues to oxygen deprivation. HIF-1 is frequently overexpressed in cancer cells, where it is involved in the upregulation of many genes necessary for survival. EZN-2968 is an antisense oligodeoxynucleotide that specifically targets HIF-1α, one of the subunits of HIF-1. We conducted a trial of EZN-2968 in patients with refractory solid tumors to evaluate antitumor response and to measure modulation of HIF-1α mRNA and protein levels as well as HIF-1 target genes.
methodsAdult patients with refractory advanced solid tumors were administered EZN-2968 as a 2-h IV infusion at a dose of 18 mg/kg once a week for three consecutive weeks followed by 3-week off; in a 6-week cycle. Tumor biopsies and dynamic contrast enhanced MRI (DCE-MRI) were performed at baseline and after the third dose.
resultsTen patients were enrolled, of whom all were evaluable for response; one patient with a duodenal neuroendocrine tumor had prolonged stabilization of disease (24 weeks). Reduction in HIF-1α mRNA levels compared to baseline was demonstrated in 4 of 6 patients with paired tumor biopsies. Reductions in levels of HIF-1α protein and mRNA levels of some target genes were observed in two patients. Quantitative analysis of DCE-MRI from two patients revealed changes in K (trans) and k ep. The trial was closed prematurely when the sponsor suspended development of this agent.
conclusionThis trial provides preliminary proof of concept for modulation of HIF-1α mRNA and protein expression and target genes in tumor biopsies following the administration of EZN-2968.
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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.