ArticleJournal of hematology & oncology2023
Safety and activity of the first-in-class locked nucleic acid (LNA) miR-221 selective inhibitor in refractory advanced cancer patients: a first-in-human, phase 1, open-label, dose-escalation study.
Article in Journal of hematology & oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04811898 (A Dose Escalation Phase I Study of LNA-i-miR-221 for the Treatment of Refractory Multiple Myeloma and Advanced Solid Tumors), which is not on this map. Cited by 46 papers, 2 of them syntheses 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.
A Dose Escalation Phase I Study of LNA-i-miR-221 for the Treatment of Refractory Multiple Myeloma and Advanced Solid Tumors
Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- A systematic review of non-coding RNA therapeutics in early clinical trials: a new perspective against cancer.Journal of translational medicine · 2024Pooled it
- Global research landscape and emerging trends of non-coding RNAs in prostate cancer: a bibliometric analysis.Frontiers in pharmacology · 2024Pooled it
- A Pan-Cancer Analysis of microRNA Tissue Specificity and Its Association with Dysregulation.International journal of molecular sciences · 2026Article
- Meta-analysis of adverse events in clinical studies with antisense oligonucleotide therapies.Molecular therapy. Nucleic acids · 2026Review
- Targeting lncRNAs to Overcome Cancer Therapy Resistance: Advances in RNA Therapeutics and Delivery Strategies.Cancers · 2026Review
- Targeting Spatiotemporal Heterogeneity of oncomiRNAs: A New Frontier in Cancer Therapy.Cancer reports (Hoboken, N.J.) · 2026Review
- Circulating miR-221/222 and Serum IL-23 in Treatment-Naïve Multiple Sclerosis: A Case-Control Study.Medicina (Kaunas, Lithuania) · 2026Observational
- MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.Neural regeneration research · 2026Article
- Emerging role of microRNAs as modulators of the tumor immune microenvironment.Journal for immunotherapy of cancer · 2026Review
- Panel-Wide Screening of Tumour Cells of Diverse Histogenesis for Responsiveness to Silencing of miR-21, miR-17, and miR-155 by Mesyl Phosphoramidate Antisense Oligonucleotides.International journal of molecular sciences · 2026Article
- Review
- MicroRNAs in oncology: a translational perspective in the era of AI.Nature reviews. Clinical oncology · 2026Review
- Identification of ceRNA Regulatory Networks Driven by the lncRNA NEAT1 in Multiple Myeloma.Journal of cellular and molecular medicine · 2026Article
- RNA Therapeutics in Viral Infections and Cancer: Mechanisms, Challenges, and Prospects: A Review.Pharmaceutics · 2026Review
- miRNA-driven cancer cell plasticity, tolerance and therapy resistance: lessons from melanoma.Molecular cancer · 2026Review
- The harmonies played by miR-302/367 cluster in pluripotency, reprogramming, and rejuvenation.Stem cells translational medicine · 2026Review
- Targeted Inhibition of Oncogenic microRNAs miR-21, miR-17, and miR-155 Suppresses Tumor Growth and Modulates Immune Response in Colorectal Cancer.Pharmaceutics · 2026Article
- miRNA in the Progression of Diabetic Kidney Disease: New Insight.International journal of molecular sciences · 2025Review
- CUL4B promotes hepatocellular carcinoma progression and oxaliplatin resistance by facilitating FUS degradation.Cell death & disease · 2025Article
- miR-96-5p-mediated Inhibition of CD47 contributes to pancreatic tumor regression via activating both innate and adaptive anti-tumor immunity.Cell communication and signaling : CCS · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe developed a 13-mer locked nucleic acid (LNA) inhibitor of miR-221 (LNA-i-miR-221) with a full phosphorothioate (PS)-modified backbone. This agent downregulated miR-221, demonstrated anti-tumor activity against human xenografts in mice, and favorable toxicokinetics in rats and monkeys. Allometric interspecies scaling allowed us to define the first-in-class LNA-i-miR-221 safe starting dose for the clinical translation.
methodsIn this first-in-human, open-label, dose-escalation phase 1 trial, we enrolled progressive cancer patients (aged ≥ 18 years) with ECOG 0-2 into 5 cohorts. The treatment cycle was based on a 30-min IV infusion of LNA-i-miR-221 on 4 consecutive days. Three patients within the first cohort were treated with 2 cycles (8 infusions), while 14 patients were treated with a single course (4 infusions); all patients were evaluated for phase 1 primary endpoint. The study was approved by the Ethics Committee and Regulatory Authorities (EudraCT 2017-002615-33).
resultsSeventeen patients received the investigational treatment, and 16 were evaluable for response. LNA-i-miR-221 was well tolerated, with no grade 3-4 toxicity, and the MTD was not reached. We recorded stable disease (SD) in 8 (50.0%) patients and partial response (PR) in 1 (6.3%) colorectal cancer case (total SD + PR: 56.3%). Pharmacokinetics indicated non-linear drug concentration increase across the dose range. Pharmacodynamics demonstrated concentration-dependent downregulation of miR-221 and upregulation of its CDKN1B/p27 and PTEN canonical targets. Five mg/kg was defined as the recommended phase II dose.
conclusionsThe excellent safety profile, the promising bio-modulator, and the anti-tumor activity offer the rationale for further clinical investigation of LNA-i-miR-221 (ClinTrials.Gov: NCT04811898).
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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.