Trial reportBritish journal of haematology2016
Marizomib irreversibly inhibits proteasome to overcome compensatory hyperactivation in multiple myeloma and solid tumour patients.
Trial report in British journal of haematology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Marizomib in the therapy of brain tumors-how far did we go and where do we stand?Pharmacological reports : PR · 2025Review
- Proteasome inhibitor bortezomib prevents proliferation and migration of pulmonary arterial smooth muscle cells.The Kaohsiung journal of medical sciences · 2024Article
- Marine-Derived Anticancer Agents Targeting Apoptotic Pathways: Exploring the Depths for Novel Cancer Therapies.Marine drugs · 2024Review
- Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors.Cell communication and signaling : CCS · 2024Review
- Article
- Evolution of Natural Product Scaffolds as Potential Proteasome Inhibitors in Developing Cancer Therapeutics.Metabolites · 2023Review
- Natural Agents as Novel Potential Source of Proteasome Inhibitors with Anti-Tumor Activity: Focus on Multiple Myeloma.Molecules (Basel, Switzerland) · 2023Review
- Computational Approaches to Enzyme Inhibition by Marine Natural Products in the Search for New Drugs.Marine drugs · 2023Review
- Glioblastoma: Current Status, Emerging Targets, and Recent Advances.Journal of medicinal chemistry · 2022Review
- Review
- Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.Molecules (Basel, Switzerland) · 2022Review
- Combined treatment of marizomib and cisplatin modulates cervical cancer growth and invasion and enhances antitumor potentialFrontiers in oncology · 2022Article
- Article
- The Role of Proteasome Inhibitors in Treating Acute Lymphoblastic Leukaemia.Frontiers in oncology · 2021Review
- Recent insights how combined inhibition of immuno/proteasome subunits enables therapeutic efficacy.Genes and immunity · 2020Review
- Recent Advances in Molecular Docking for the Research and Discovery of Potential Marine Drugs.Marine drugs · 2020Review
- Advances in Deubiquitinating Enzyme Inhibition and Applications in Cancer Therapeutics.Cancers · 2020Review
- Drug Development Targeting the Ubiquitin-Proteasome System (UPS) for the Treatment of Human Cancers.Cancers · 2020Review
- Marizomib suppresses triple-negative breast cancer via proteasome and oxidative phosphorylation inhibition.Theranostics · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteasome inhibitors (PIs) are highly active in multiple myeloma (MM) but resistance is commonly observed. All clinical stage PIs effectively inhibit chymotrypsin-like (CT-L) activity; one possible mechanism of resistance is compensatory hyperactivation of caspase-like (C-L) and trypsin-like (T-L) subunits, in response to CT-L blockade. Marizomib (MRZ), an irreversible PI that potently inhibits all three 20S proteasome subunits with a specificity distinct from other PIs, is currently in development for treatment of MM and malignant glioma. The pan-proteasome pharmacodynamic activity in packed whole blood and peripheral blood mononuclear cells was measured in two studies in patients with advanced solid tumours and haematological malignancies. Functional inhibition of all proteasome subunits was achieved with once- or twice-weekly MRZ dosing; 100% inhibition of CT-L was frequently achieved within one cycle at therapeutic doses. Concomitantly, C-L and T-L activities were either unaffected or increased, suggesting compensatory hyperactivation of these subunits. Importantly, this response was overcome by continued administration of MRZ, with robust inhibition of T-L and C-L (up to 80% and 50%, respectively) by the end of Cycle 2 and maintained thereafter. This enhanced proteasome inhibition was independent of tumour type and may underlie the clinical activity of MRZ in patients resistant to other PIs.
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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.