ArticleThe Journal of clinical investigation2018
DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 28 citations in OpenAlex.
- Targeting NAD + biosynthesis suppresses TGF-β1/Smads/RAB26 axis and potentiates cisplatin cytotoxicity in non-small cell lung cancer brain metastasis.Acta neuropathologica communications · 2025Article
- NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma.Blood advances · 2025Article
- NAMPT-Driven M2 Polarization of Tumor-Associated Macrophages Leads to an Immunosuppressive Microenvironment in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Development of PARP inhibitors in advanced prostate cancer.Therapeutic advances in medical oncology · 2024Review
- Homozygous CRISPR/Cas9 Knockout Generated a Novel Functionally Active Exon 1 Skipping XPA Variant in Melanoma Cells.International journal of molecular sciences · 2022Article
- XRCC1 counteracts poly(ADP ribose)polymerase (PARP) poisons, olaparib and talazoparib, and a clinical alkylating agent, temozolomide, by promoting the removal of trapped PARP1 from broken DNA.Genes to cells : devoted to molecular & cellular mechanisms · 2022Article
- Advances in NAD-Lowering Agents for Cancer Treatment.Nutrients · 2021Review
- NADProceedings of the National Academy of Sciences of the United States of America · 2021Article
- ATM Inhibitor Suppresses Gemcitabine-Resistant BTC Growth in a Polymerase θ Deficiency-Dependent Manner.Biomolecules · 2020Article
- Article
- Compromised DNA repair is responsible for diabetes-associated fibrosis.The EMBO journal · 2020Article
- A decade of clinical development of PARP inhibitors in perspective.Annals of oncology : official journal of the European Society for Medical Oncology · 2019Review
- Subcellular compartmentalization of NADPharmacology & therapeutics · 2019Review
- PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer.The Journal of clinical investigation · 2019Article
- Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
26 authors at 7 institutions in 3 countries.
Funding
Abstract
Synthetic lethality is an efficient mechanism-based approach to selectively target DNA repair defects. Excision repair cross-complementation group 1 (ERCC1) deficiency is frequently found in non-small-cell lung cancer (NSCLC), making this DNA repair protein an attractive target for exploiting synthetic lethal approaches in the disease. Using unbiased proteomic and metabolic high-throughput profiling on a unique in-house-generated isogenic model of ERCC1 deficiency, we found marked metabolic rewiring of ERCC1-deficient populations, including decreased levels of the metabolite NAD+ and reduced expression of the rate-limiting NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT). We also found reduced NAMPT expression in NSCLC samples with low levels of ERCC1. These metabolic alterations were a primary effect of ERCC1 deficiency, and caused selective exquisite sensitivity to small-molecule NAMPT inhibitors, both in vitro - ERCC1-deficient cells being approximately 1,000 times more sensitive than ERCC1-WT cells - and in vivo. Using transmission electronic microscopy and functional metabolic studies, we found that ERCC1-deficient cells harbor mitochondrial defects. We propose a model where NAD+ acts as a regulator of ERCC1-deficient NSCLC cell fitness. These findings open therapeutic opportunities that exploit a yet-undescribed nuclear-mitochondrial synthetic lethal relationship in NSCLC models, and highlight the potential for targeting DNA repair/metabolic crosstalks for cancer therapy.
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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.