ArticleScientific reports2019
H727 cells are inherently resistant to the proteasome inhibitor carfilzomib, yet require proteasome activity for cell survival and growth.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized by Polycationic Complexation.Journal of pharmaceutical sciences · 2024Article
- Insulin-Degrading Enzyme Is a Non Proteasomal Target of Carfilzomib and Affects the 20S Proteasome Inhibition by the Drug.Biomolecules · 2022Article
- Proteasomal adaptations to FDA-approved proteasome inhibitors: a potential mechanism for drug resistance?Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Proteasome Complexes and Their Heterogeneity in Colorectal, Breast and Pancreatic Cancers.Journal of Cancer · 2021Article
- Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma.Frontiers in oncology · 2021Review
- Neuroendocrine Lung Cancer Mouse Models: An Overview.Cancers · 2020Review
- Synthesis and Application of an Activity-Based Peptide-Peptoid Hybrid Probe for the Immunoproteasome.Current protocols in chemical biology · 2019Article
- Development of Novel Epoxyketone-Based Proteasome Inhibitors as a Strategy To Overcome Cancer Resistance to Carfilzomib and Bortezomib.Journal of medicinal chemistry · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The second-in-class proteasome inhibitor (PI) carfilzomib (Kyprolis, Cfz) has contributed to a substantial advancement in multiple myeloma treatment by improving patient survival and quality of life. A considerable portion of patients however display intrinsic resistance to Cfz. Our mechanistic understanding of intrinsic Cfz resistance is limited due to a lack of suitable cell-based models. We report that H727 human bronchial carcinoid cells are inherently resistant to Cfz, yet susceptible to other PIs and inhibitors targeting upstream components of the ubiquitin-proteasome system (UPS). These results indicate that H727 cells remain dependent on the UPS for cell survival and growth despite harboring intrinsic resistance to Cfz. Alterations in the composition of proteasome catalytic subunits via interferon-γ treatment or siRNA knockdown results in sensitization of H727 cells to Cfz. We postulate that a potential link may exist between the composition of proteasome catalytic subunits and the cellular response to Cfz. Overall, H727 cells may serve as a useful cell-based model for de novo Cfz resistance and our results suggest previously unexplored mechanisms of de novo PI resistance.
Indexed as
Identifiers
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.