ArticleMolecular cancer therapeutics2013
NF-κB inhibition by bortezomib permits IFN-γ-activated RIP1 kinase-dependent necrosis in renal cell carcinoma.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Pooled it
- An exploratory clinical trial of bortezomib in patients with lower risk myelodysplastic syndromes.American journal of hematology · 2017Trial
- Development of a Mitochondrial Permeability Transition-Driven Necrosis-Related Prognostic Signature in Cervical Cancer: Integrating Bulk Transcriptomic and Single-Cell Data.Cancer medicine · 2025Article
- Proteasome inhibitor-associated thrombotic microangiopathy: a real-world retrospective and pharmacovigilance database analysis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Article
- Bortezomib suppresses acute myelogenous leukaemia stem-like KG-1a cells via NF-κB inhibition and the induction of oxidative stress.Journal of cellular and molecular medicine · 2024Article
- Frontier knowledge and future directions of programmed cell death in clear cell renal cell carcinoma.Cell death discovery · 2024Review
- No Time to Die: How Kidney Cancer Evades Cell Death.International journal of molecular sciences · 2022Review
- Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses.Molecular systems biology · 2021Article
- Management of nephrotoxicity of chemotherapy and targeted agents: 2020.American journal of cancer research · 2020Review
- Complex roles of necroptosis in cancer.Journal of Zhejiang University. Science. B · 2019Review
- Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy.Cancer cell international · 2019Review
- Cell death-based approaches in treatment of the urinary tract-associated diseases: a fight for survival in the killing fields.Cell death & disease · 2018Review
- Proteasome inhibitor bortezomib enhances the effect of standard chemotherapy in small cell lung cancer.Oncotarget · 2017Article
- Thrombotic microangiopathy associated with proteasome inhibitors.Clinical kidney journal · 2015Review
- Manipulation of apoptosis and necroptosis signaling by herpesviruses.Medical microbiology and immunology · 2015Review
- New miRNA profiles accurately distinguish renal cell carcinomas and upper tract urothelial carcinomas from the normal kidney.PloS one · 2014Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Advanced renal cell carcinoma (RCC) is an invariably fatal cancer. Currently, small-molecule inhibitors that target cell growth, angiogenesis, or nutrient-sensing pathways represent the primary pharmacologic interventions for this disease, but these inhibitors only delay tumor progression and are not curative. The cytokine IFN-γ showed the potential to provide lasting remission in several phase I/II trials for advanced RCCs, but subsequent trials, including a multicenter phase III study using IFN-γ as a monotherapy for RCCs, were less promising. Notably, these trials were designed to exploit the indirect immunomodulatory effects of IFN-γ, whereas its direct antitumor properties--including its ability to trigger programmed cell death in tumors-remain mostly untapped. Here, we show that the proteasome inhibitor bortezomib (PS-341, Velcade) sensitizes otherwise resistant RCC cells to direct necrotic death by IFN-γ. Mechanistically, we show that bortezomib functions, at least in part, by inhibiting prosurvival NF-κB signaling. In the absence of this signal, IFN-γ triggers programmed necrosis (or "necroptosis") dependent on the kinase RIP1. When taken together with the observation that NF-κB signaling is elevated in RCCs, these results provide rationale for the combined use of IFN-γ and bortezomib in the treatment of metastatic RCCs.
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Registered trials
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