ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Carfilzomib and ONX 0912 inhibit cell survival and tumor growth of head and neck cancer and their activities are enhanced by suppression of Mcl-1 or autophagy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Marizomib in the therapy of brain tumors-how far did we go and where do we stand?Pharmacological reports : PR · 2025Review
- Combination effects of Pistachio hull and carfilzomib on NF-κB p65, MDR1, MRP1, and Caspase3 gene expression in breast cancer cell line.BMC complementary medicine and therapies · 2025Article
- Proteasome: Role in T Cell Function Regulation.International journal of biological sciences · 2025Review
- Bioinformatics-based analysis of nicotinamide adenine dinucleotide metabolism-related genes to predict immune status and prognosis for head and neck squamous cell carcinoma patients.Frontiers in immunology · 2025Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- The role of proteasomes in tumorigenesis.Genes & diseases · 2024Review
- Preclinical efficacy of carfilzomib in BRAF-mutant colorectal cancer models.Molecular oncology · 2024Article
- Crosstalk between metabolism and cell death in tumorigenesis.Molecular cancer · 2024Review
- Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized by Polycationic Complexation.Journal of pharmaceutical sciences · 2024Article
- PI3K/AKT Signaling Pathway Mediated Autophagy in Oral Carcinoma - A Comprehensive Review.International journal of medical sciences · 2024Review
- UBE3A: The Role in Autism Spectrum Disorders (ASDs) and a Potential Candidate for Biomarker Studies and Designing Therapeutic Strategies.Diseases (Basel, Switzerland) · 2023Review
- Autophagy: A Potential Therapeutic Target to Tackle Drug Resistance in Multiple Myeloma.International journal of molecular sciences · 2023Review
- ONX-0914 Induces Apoptosis and Autophagy with p53 Regulation in Human Glioblastoma Cells.Cancers · 2022Article
- Myeloid cell leukemia-1 expression in cancers of the oral cavity: a scoping review.Cancer cell international · 2022Article
- Synergistic PIM kinase and proteasome inhibition as a therapeutic strategy for MYC-overexpressing triple-negative breast cancer.Cell chemical biology · 2022Article
- Mitochondrial dysfunction, UPRCell & bioscience · 2021Review
- Carfilzomib in Combination with Bortezomib Enhances Apoptotic Cell Death in B16-F1 Melanoma Cells.Biology · 2021Article
- Auto-HMM-LMF: feature selection based method for prediction of drug response via autoencoder and hidden Markov model.BMC bioinformatics · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
purposeCarfilzomib is a selective, irreversible inhibitor of the chymotrypsin-like activity of the proteasome and is undergoing clinical evaluation in myeloma. ONX 0912 (oprozomib) is an orally bioavailable derivative. The activities of carfilzomib and ONX 0912 against solid tumor malignancies are less well understood. We investigated the impact and mechanisms of action of carfilzomib and ONX 0912 in preclinical models of head and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL
designThe effects of carfilzomib and ONX 0912 on HNSCC cell survival and xenograft tumor growth were evaluated. The impact and mechanisms of both agents on apoptosis and autophagy induction were also investigated. The contribution of the unfolded protein response (UPR) to autophagy induction and the role of autophagy in attenuating HNSCC cell death were determined.
resultsCarfilzomib and ONX 0912 potently induced apoptosis in HNSCC cell lines via upregulation of pro-apoptotic Bik. Upregulation of Mcl-1 by these agents served to dampen their efficacies. Carfilzomib and ONX 0912 also induced autophagy, mediated, in part, by activation of the UPR pathway involving upregulation of ATF4 transcription factor. Autophagy induction served a prosurvival role. Oral administration of ONX 0912 inhibited the growth of HNSCC xenograft tumors in a dose-dependent manner.
conclusionsThese results show that carfilzomib and ONX 0912 are potently active against HNSCC cells, and the activities of these agents can be enhanced via suppression of Mcl-1 or inhibition of autophagy. Oral ONX 0912 exhibits in vivo activity against HNSCC tumors and may represent a useful therapeutic agent for this malignancy.
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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.