ArticleInvestigational new drugs2012
Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination.
Article in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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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.
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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
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Combination therapy in combating cancer.Oncotarget · 2017Pooled it
- Marizomib irreversibly inhibits proteasome to overcome compensatory hyperactivation in multiple myeloma and solid tumour patients.British journal of haematology · 2016Trial
- Targeting HDAC and proteostasis to eradicate quiescent cancer cells.Cancer gene therapy · 2026Article
- Proteasome Inhibitor-Induced Cytotoxic Mechanisms in Canine Pulmonary Adenocarcinoma Cell Lines.Veterinary and comparative oncology · 2026Article
- Marizomib in the therapy of brain tumors-how far did we go and where do we stand?Pharmacological reports : PR · 2025Review
- Prospects and challenges of novel natural marine-derived compounds in melanoma treatment.World journal of clinical oncology · 2025Review
- Advances in pancreatic cancer epigenetics: From the mechanism to the clinic.World journal of gastrointestinal oncology · 2025Review
- Mechanistic Insights and Therapeutic Potentials of Ubiquitin-Proteasome System in Non-Small Cell Lung Cancer.Cell proliferation · 2025Review
- Marizomib Promotes Senescence or Long-Term Apoptosis in Melanoma Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Marizomib (Salinosporamide A) Promotes Apoptosis in A375 and G361 Melanoma Cancer Cells.Marine drugs · 2024Article
- Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat.Heliyon · 2024Review
- Marine-Derived Anticancer Agents Targeting Apoptotic Pathways: Exploring the Depths for Novel Cancer Therapies.Marine drugs · 2024Review
- Article
- Evolution of Natural Product Scaffolds as Potential Proteasome Inhibitors in Developing Cancer Therapeutics.Metabolites · 2023Review
- Molecular Research in Pancreatic Cancer: Small Molecule Inhibitors, Their Mechanistic Pathways and Beyond.Current issues in molecular biology · 2023Review
- Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment.Cancers · 2022Review
- Epigenetic regulation of pancreatic adenocarcinoma in the era of cancer immunotherapy.Journal of gastroenterology · 2022Review
- Marine-Inspired Drugs and Biomaterials in the Perspective of Pancreatic Cancer Therapies.Marine drugs · 2022Review
- Marine Compounds for Melanoma Treatment and Prevention.International journal of molecular sciences · 2022Review
- Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.Molecules (Basel, Switzerland) · 2022Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeCombining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested utility in combining it with an HDAC inhibitor such as vorinostat. Thus, in this study in vitro studies assessed the potential utility of combining marizomib and vorinostat, followed by a clinical trial with the objectives of assessing the recommended phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), safety and preliminary anti-tumor activity of the combination in patients. EXPERIMENTAL
designCombinations of marizomib and vorinostat were assessed in vitro. Subsequently, in a Phase 1 clinical trial patients with melanoma, pancreatic carcinoma or Non-small Cell Lung Cancer (NSCLC) were given escalating doses of weekly marizomib in combination with vorinostat 300 mg daily for 16 days in 28 day cycles. In addition to standard safety studies, proteasome inhibition and pharmacokinetics were assayed.
resultsMarked synergy of marizomib and vorinostat was seen in tumor cell lines derived from patients with NSCLC, melanoma and pancreatic carcinoma. In the clinical trial, 22 patients were enrolled. Increased toxicity was not seen with the combination. Co-administration did not appear to affect the PK or PD of either drug in comparison to historical data. Although no responses were demonstrated using RECIST criteria, 61% of evaluable patients demonstrated stable disease with 39% having decreases in tumor measurements.
conclusionsTreatment of multiple tumor cell lines with marizomib and vorinostat resulted in a highly synergistic antitumor activity. The combination of full dose marizomib with vorinostat is tolerable in patients with safety findings consistent with either drug alone.
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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.