ArticleBlood2013
Intracellular NAD⁺ depletion enhances bortezomib-induced anti-myeloma activity.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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.
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
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Importance of circulating adipocytokines in multiple myeloma: a systematic review and meta-analysis based on case-control studies.BMC endocrine disorders · 2022Pooled it
- Article
- Inhibition of NAMPT targets DNA damage response to sensitize alkylating chemotherapy in TP53 mutant mantle cell lymphoma.Blood advances · 2026Article
- A rabbit anti-human CD38 antibody for eliminating daratumumab and isatuximab interference in immunohematology testing.Frontiers in immunology · 2026Article
- Unraveling Obesity and Multiple Myeloma: Insights from Epidemiology and Molecular Mechanisms.Current obesity reports · 2025Review
- NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma.Blood advances · 2025Article
- Regulation of ubiquitin-proteasome system and its relative pathways in pancreatic adenocarcinoma.BioImpacts : BI · 2025Review
- Interplay between proteasome function and inflammatory responses in e-cig vapor condensate-challenged lung epithelial cells.Archives of toxicology · 2023Article
- Anticancer Activities of Novel Nicotinamide Phosphoribosyltransferase Inhibitors in Hematological Malignancies.Molecules (Basel, Switzerland) · 2023Article
- CD38-Induced Metabolic Dysfunction Primes Multiple Myeloma Cells for NADAntioxidants (Basel, Switzerland) · 2023Article
- Obesity as a risk factor for multiple myeloma: insight on the role of adipokines.Pathology oncology research : POR · 2023Review
- Discovery of a novel NAMPT inhibitor that selectively targets NAPRT-deficient EMT-subtype cancer cells and alleviates chemotherapy-induced peripheral neuropathy.Theranostics · 2023Article
- NAD/NAMPT and mTOR Pathways in Melanoma: Drivers of Drug Resistance and Prospective Therapeutic Targets.International journal of molecular sciences · 2022Review
- Race for the Cure: From the Oldest to the Newest Monoclonal Antibodies for Multiple Myeloma Treatment.Biomolecules · 2022Review
- Review
- NAD+ depletion enhances reovirus-induced oncolysis in multiple myeloma.Molecular therapy oncolytics · 2022Article
- secDrug: a pipeline to discover novel drug combinations to kill drug-resistant multiple myeloma cells using a greedy set cover algorithm and single-cell multi-omics.Blood cancer journal · 2022Article
- Article
- Review of various NAMPT inhibitors for the treatment of cancer.Frontiers in pharmacology · 2022Review
- Advances in NAD-Lowering Agents for Cancer Treatment.Nutrients · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
We recently demonstrated that Nicotinamide phosphoribosyltransferase (Nampt) inhibition depletes intracellular NAD⁺ content leading, to autophagic multiple myeloma (MM) cell death. Bortezomib has remarkably improved MM patient outcome, but dose-limiting toxicities and development of resistance limit its long-term utility. Here we observed higher Nampt messenger RNA levels in bortezomib-resistant patient MM cells, which correlated with decreased overall survival. We demonstrated that combining the NAD⁺ depleting agent FK866 with bortezomib induces synergistic anti-MM cell death and overcomes bortezomib resistance. This effect is associated with (1) activation of caspase-8, caspase-9, caspase-3, poly (ADP-ribose) polymerase, and downregulation of Mcl-1; (2) enhanced intracellular NAD⁺ depletion; (3) inhibition of chymotrypsin-like, caspase-like, and trypsin-like proteasome activities; (4) inhibition of nuclear factor κB signaling; and (5) inhibition of angiogenesis. Furthermore, Nampt knockdown significantly enhances the anti-MM effect of bortezomib, which can be rescued by ectopically overexpressing Nampt. In a murine xenograft MM model, low-dose combination FK866 and Bortezomib is well tolerated, significantly inhibits tumor growth, and prolongs host survival. Taken together, these findings indicate that intracellular NAD⁺ level represents a major determinant in the ability of bortezomib to induce apoptosis in MM cells and provide proof of concept for the combination with FK866 as a new strategy to enhance sensitivity or overcome resistance to bortezomib.
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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.