ArticleScientific reports2023
Inhibition of nicotinamide dinucleotide salvage pathway counters acquired and intrinsic poly(ADP-ribose) polymerase inhibitor resistance in high-grade serous ovarian cancer.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Physicochemical and Metabolic Optimization of NAMPT Inhibitors Enables Effective Antibody-Drug Conjugates for Liquid and Solid Tumors.ACS bio & med chem Au · 2026Article
- RLASON-CDR: a reinforcement learning-driven adaptive synergistic optimization network for cancer drug response prediction.Briefings in bioinformatics · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- Exploiting synthetic lethality in epithelial ovarian cancer: multi-dimensional approaches beyond DNA damage repair.Molecular cancer · 2026Review
- Inhibiting Nampt signaling promotes M2 macrophage polarization to enhance bone regeneration in periodontitis.Frontiers in bioengineering and biotechnology · 2026Article
- RAS/PI3K pathway mutations sensitise epithelial ovarian cancer cells to a PARP/NAMPT inhibitor combination.Communications biology · 2025Article
- PARP Activity Is Essential for Retinal Photoreceptor Survival in the Human Homologous RhoJournal of neurochemistry · 2025Article
- Targeting FEN1/EXO1 to enhance efficacy of PARP inhibition in triple-negative breast cancer.Translational oncology · 2025Article
- A Novel Insight into the Role of Obesity-Related Adipokines in Ovarian Cancer-State-of-the-Art Review and Future Perspectives.International journal of molecular sciences · 2025Review
- Identification of a Novel 4-gene Prognostic Model Related to Neutrophil Extracellular Traps for Colorectal Cancer.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024Article
- Biological Functions and Therapeutic Potential of NADCancers · 2024Review
- Targeting NAD Metabolism: Rational Design, Synthesis and In Vitro Evaluation of NAMPT/PARP1 Dual-Target Inhibitors as Anti-Breast Cancer Agents.Molecules (Basel, Switzerland) · 2024Article
- Channeling Nicotinamide Phosphoribosyltransferase (NAMPT) to Address Life and Death.Journal of medicinal chemistry · 2024Review
- Research progress on the application of organoids in gynecological tumors.Frontiers in pharmacology · 2024Review
- NAD metabolism: Role in senescence regulation and aging.Aging cell · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial ovarian cancer is the most lethal gynecological malignancy, owing notably to its high rate of therapy-resistant recurrence in spite of good initial response to chemotherapy. Although poly(ADP-ribose) polymerase inhibitors (PARPi) have shown promise for ovarian cancer treatment, extended therapy usually leads to acquired PARPi resistance. Here we explored a novel therapeutic option to counter this phenomenon, combining PARPi and inhibitors of nicotinamide phosphoribosyltransferase (NAMPT). Cell-based models of acquired PARPi resistance were created through an in vitro selection procedure. Using resistant cells, xenograft tumors were grown in immunodeficient mice, while organoid models were generated from primary patient tumor samples. Intrinsically PARPi-resistant cell lines were also selected for analysis. Our results show that treatment with NAMPT inhibitors effectively sensitized all in vitro models to PARPi. Adding nicotinamide mononucleotide, the resulting NAMPT metabolite, abrogated the therapy-induced cell growth inhibition, demonstrating the specificity of the synergy. Treatment with olaparib (PARPi) and daporinad (NAMPT inhibitor) depleted intracellular NAD+ , induced double-strand DNA breaks, and promoted apoptosis as monitored by caspase-3 cleavage. The two drugs were also synergistic in mouse xenograft models and clinically relevant patient-derived organoids. Therefore, in the context of PARPi resistance, NAMPT inhibition could offer a promising new option for ovarian cancer patients.
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