ArticleOncotarget2016
Antitumor effect of combined NAMPT and CD73 inhibition in an ovarian cancer model.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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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.
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Who cites it
41 citing papers in PubMed, 70 citations in OpenAlex.
- Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults.Scientific reports · 2019Trial
- Purinergic Signaling in Ovarian Carcinoma.Advanced pharmaceutical bulletin · 2025Review
- Emerging strategies, applications and challenges of targeting NADNature aging · 2025Review
- A Comprehensive Multiomics Signature of Doxorubicin-Induced Cellular Senescence in the Postmenopausal Human Ovary.Aging cell · 2025Article
- Biological Functions and Therapeutic Potential of NADCancers · 2024Review
- Regulation of CD73 on NAD metabolism: Unravelling the interplay between tumour immunity and tumour metabolism.Cell communication and signaling : CCS · 2024Review
- Distinct Capabilities in NAD Metabolism Mediate Resistance to NAMPT Inhibition in Glioblastoma.Cancers · 2024Article
- Dual-inhibition of NAMPT and PAK4 induces anti-tumor effects in 3D-spheroids model of platinum-resistant ovarian cancer.Cancer gene therapy · 2024Article
- The Role of NADPharmaceuticals (Basel, Switzerland) · 2024Review
- Inhibitors of NADInternational journal of molecular sciences · 2024Review
- Bioinformatics identifies key genes and potential drugs for energy metabolism disorders in heart failure with dilated cardiomyopathy.Frontiers in pharmacology · 2024Article
- Endosome Traffic Modulates Pro-Inflammatory Signal Transduction in CD4International journal of molecular sciences · 2023Review
- The Role of NAD+, SIRTs Interactions in Stimulating and Counteracting Carcinogenesis.International journal of molecular sciences · 2023Review
- Review
- Review
- Gut microbiota severely hampers the efficacy of NAD-lowering therapy in leukemia.Cell death & disease · 2022Article
- Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors.Aging and disease · 2021Review
- Transcriptional and Metabolic Investigation in 5'-Nucleotidase Deficient Cancer Cell Lines.Cells · 2021Article
- Characterization of Two NMN Deamidase Mutants as Possible Probes for an NMN Biosensor.International journal of molecular sciences · 2021Article
- Enzymology of extracellular NAD metabolism.Cellular and molecular life sciences : CMLS · 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
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nicotinamide phosphoribosyltransferase (NAMPT) is a crucial enzyme in the biosynthesis of intracellular NAD+. NAMPT inhibitors have potent anticancer activity in several preclinical models by depleting NAD+ and ATP levels. Recently, we demonstrated that CD73 enables the utilization of extracellular NAD+/nicotinamide mononucleotide (NMN) by converting them to Nicotinamide riboside (NR), which can cross the plasmamembrane and fuel intracellular NAD+ biosynthesis in human cells. These processes are herein confirmed to also occur in a human ovarian carcinoma cell line (OVCAR-3), by means of CD73 or NRK1 specific silencing. Next, we investigated the anti-tumor activity of the simultaneous inhibition of NAMPT (with FK866) and CD73 (with α, β-methylene adenosine 5'-diphosphate, APCP), in an in vivo human ovarian carcinoma model. Interestingly, the combined therapy was found to significantly decrease intratumor NAD+, NMN and ATP levels, compared with single treatments. In addition, the concentration of these nucleotides in ascitic exudates was more remarkably reduced in animals treated with both FK866 and APCP compared with single treatments. Importantly, tumors treated with FK866 in combination with APCP contained a statistically significant lower proportion of Ki67 positive proliferating cells and a higher percentage of necrotic area. Finally, a slight but significant increase in animal survival in response to the combined therapy, compared to the single agents, could be demonstrated. Our results indicate that the pharmacological inhibition of CD73 enzymatic activity could be considered as a means to potentiate the anti-cancer effects of NAMPT inhibitors.
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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.