ArticleBritish journal of cancer2013
First-in-human Phase I study of EZN-4176, a locked nucleic acid antisense oligonucleotide to exon 4 of the androgen receptor mRNA in patients with castration-resistant prostate cancer.
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 90 citations in OpenAlex.
- Targeting the Androgen Receptor and Associated Cofactors in Prostate Cancer: Novel Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- Meta-analysis of adverse events in clinical studies with antisense oligonucleotide therapies.Molecular therapy. Nucleic acids · 2026Review
- Circulating tumor cells in pancreatic cancer: more than liquid biopsy.Therapeutic advances in medical oncology · 2024Review
- The androgen receptor-targeted proteolysis targeting chimera and other alternative therapeutic choices in overcoming the resistance to androgen deprivation treatment in prostate cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Altered Extracellular Matrix as an Alternative Risk Factor for Epileptogenicity in Brain Tumors.Biomedicines · 2022Review
- Antitumoral RNA-targeted oligonucleotide therapeutics: The third pillar after small molecule inhibitors and antibodies.Cancer science · 2022Review
- Targeting a splicing-mediated drug resistance mechanism in prostate cancer by inhibiting transcriptional regulation by PKCβ1.Oncogene · 2022Article
- Antisense oligonucleotides targeting ORF1b block replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Frontiers in microbiology · 2022Article
- Nephrotoxic antisense oligonucleotide SPC5001 induces kidney injury biomarkers in a proximal tubule-on-a-chip.Archives of toxicology · 2021Article
- Antisense technology: an overview and prospectus.Nature reviews. Drug discovery · 2021Review
- Circulating tumor cell profiling for precision oncology.Molecular oncology · 2021Review
- The Challenges and Strategies of Antisense Oligonucleotide Drug Delivery.Biomedicines · 2021Review
- A Multifunctional LNA Oligonucleotide-Based Strategy Blocks AR Expression and Transactivation Activity in PCa Cells.Molecular therapy. Nucleic acids · 2021Article
- MicroRNAs as regulators of brain function and targets for treatment of epilepsy.Nature reviews. Neurology · 2020Review
- Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications.Medicines (Basel, Switzerland) · 2019Review
- Bridged Nucleic Acids Reloaded.Molecules (Basel, Switzerland) · 2019Review
- Dysregulated Transcriptional Control in Prostate Cancer.International journal of molecular sciences · 2019Review
- Development of Locked Nucleic Acid Antisense Oligonucleotides Targeting Ebola Viral Proteins and Host Factor Niemann-Pick C1.Nucleic acid therapeutics · 2018Article
- Liquid Biopsy in Thyroid Cancer: New Insight.International journal of hematology-oncology and stem cell research · 2018Review
- Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer.Annals of translational medicine · 2018Review
Corrections and comments
- Commented on by
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundProstate cancer remains dependent of androgen receptor (AR) signalling, even after emergence of castration resistance. EZN-4176 is a third-generation antisense oligonucleotide that binds to the hinge region (exon 4) of AR mRNA resulting in full-length AR mRNA degradation and decreased AR protein expression. This Phase I study aimed to evaluate EZN-4176 in men with castration-resistant prostate cancer (CRPC).
methodsPatients with progressing CRPC were eligible; prior abiraterone and enzalutamide treatment were allowed. EZN-4176 was administered as a weekly (QW) 1-h intravenous infusion. The starting dose was 0.5 mg kg(-1) with a 4-week dose-limiting toxicity (DLT) period and a 3+3 modified Fibonacci dose escalation design. After determination of the DLT for weekly administration, an every 2 weeks schedule was initiated.
resultsA total of 22 patients were treated with EZN-4176. At 10 mg kg(-1) QW, two DLTs were observed due to grade 3-4 ALT or AST elevation. No confirmed biochemical or soft tissue responses were observed. Of eight patients with <5 circulating tumour cells at baseline, a conversion to <5 was observed in three (38%) patients. The most common EZN-4176-related toxicities (all grades) were fatigue (59%), reversible abnormalities in liver function tests ALT (41%) and AST (41%) and infusion-related reactions including chills (36%) and pyrexia (14%).
conclusionActivity of EZN-4176 at the doses and schedules explored was minimal. The highest dose of 10 mg kg(-1) QW was associated with significant but reversible transaminase elevation.
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.