ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
A 13 mer LNA-i-miR-221 Inhibitor Restores Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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 75 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.
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
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 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
- The PPTC7/BNIP3/NIX axis induces cGAS/STING-mediated senescence and augments CAR-T efficacy by repressing tumor-intrinsic mitophagy.Journal of experimental & clinical cancer research : CR · 2026Article
- RNA-Based Therapeutic Strategies in Multiple Myeloma: From Molecular Targets to Delivery and Clinical Translation.International journal of molecular sciences · 2026Review
- Circulating extracellular vesicle isomiR signatures predict therapy response in patients with multiple myeloma.Cell reports. Medicine · 2025Article
- MicroRNA in cancer therapy: breakthroughs and challenges in early clinical applications.Journal of experimental & clinical cancer research : CR · 2025Review
- Refining precision prognostics in multiple myeloma: loss of miR-221/222 cluster in CD138+ plasma cells results in short-term progression and worse treatment outcome.Blood cancer journal · 2025Article
- LNA-i-miR-221 activity in colorectal cancer: A reverse translational investigation.Molecular therapy. Nucleic acids · 2024Article
- Beneficial Effect of Olive Oil and Its Derivates: Focus on Hematological Neoplasm.Life (Basel, Switzerland) · 2024Review
- Drug resistance mechanisms in cancers: Execution of pro-survival strategies.Journal of biomedical research · 2024Article
- TP63 transcriptionally regulates SLC7A5 to suppress ferroptosis in head and neck squamous cell carcinoma.Frontiers in immunology · 2024Article
- Scaling approaches for the prediction of human clearance of LNA-i-mir-221: A retrospective validation.Current research in pharmacology and drug discovery · 2024Article
- Dysregulation of Non-Coding RNAs: Roles of miRNAs and lncRNAs in the Pathogenesis of Multiple Myeloma.Non-coding RNA · 2023Review
- 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.Journal of hematology & oncology · 2023Article
- Review
- High serum miR-223-3p expression level predicts complete response and prolonged overall survival in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation.Frontiers in oncology · 2023Article
- MiRNA as a Potential Target for Multiple Myeloma Therapy-Current Knowledge and Perspectives.Journal of personalized medicine · 2022Review
- Review
- miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review.Molecular therapy. Nucleic acids · 2022Review
- Multiple Myeloma: Challenges Encountered and Future Options for Better Treatment.International journal of molecular sciences · 2022Review
- Roles of miRNA dysregulation in the pathogenesis of multiple myeloma.Cancer gene therapy · 2021Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeThe onset of drug resistance is a major cause of treatment failure in multiple myeloma. Although increasing evidence is defining the role of miRNAs in mediating drug resistance, their potential activity as drug-sensitizing agents has not yet been investigated in multiple myeloma. EXPERIMENTAL
designHere we studied the potential utility of miR-221/222 inhibition in sensitizing refractory multiple myeloma cells to melphalan.
resultsmiR-221/222 expression inversely correlated with melphalan sensitivity of multiple myeloma cells. Inhibition of miR-221/222 overcame melphalan resistance and triggered apoptosis of multiple myeloma cells in vitro, in the presence or absence of human bone marrow (BM) stromal cells. Decreased multiple myeloma cell growth induced by inhibition of miR-221/222 plus melphalan was associated with a marked upregulation of pro-apoptotic BBC3/PUMA protein, a miR-221/222 target, as well as with modulation of drug influx-efflux transporters SLC7A5/LAT1 and the ABC transporter ABCC1/MRP1. Finally, in vivo treatment of SCID/NOD mice bearing human melphalan-refractory multiple myeloma xenografts with systemic locked nucleic acid (LNA) inhibitors of miR-221 (LNA-i-miR-221) plus melphalan overcame drug resistance, evidenced by growth inhibition with significant antitumor effects together with modulation of PUMA and ABCC1 in tumors retrieved from treated mice.
conclusionsTaken together, our findings provide the proof of concept that LNA-i-miR-221 can reverse melphalan resistance in preclinical models of multiple myeloma, providing the framework for clinical trials to overcome drug resistance, and improve patient outcome in multiple myeloma.
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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.