{
  "abstract": "Nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in NAD biosynthesis, is a potential therapeutic target in cancer. Acute myeloid leukemia (AML) is among cancer types exhibiting high NAMPT dependence, and elevated NAMPT activity is implicated in venetoclax resistance. Thus, pharmacologic NAMPT inhibitors (NAMPTi) have been developed as a promising therapeutic approach in some cancers. However, our current knowledge of in vivo factors that determine NAMPTi therapeutic efficacy is incomplete. In this study, using mouse models we found that NAMPTi efficacy against AML is limited by dietary nicotinic acid (NA). Specifically, NA and NA riboside (NAR), an NA-derived metabolite, promoted NAD biosynthesis independent of NAMPT and rescued AML cells from NAMPTi-mediated toxicity in vitro. Importantly, in AML xenograft models, dietary NA restriction, which selectively reduces circulating NAR levels, enhanced antitumor efficacy of NAMPTis and prolonged animal survival. Although the combination treatment caused transient hematologic toxicity, peripheral blood cell counts largely recovered after treatment. Our findings highlight systemic NAD precursor metabolism, including NAR, as a determinant of responses to NAMPT-targeted therapies. We conclude that NA restriction may improve the therapeutic efficacy of NAMPTis in AML.\n\nSignificance:: NAMPT is a potential therapeutic target in AML, but factors governing treatment response remain undefined. Building on findings that dietary NA maintains circulating NAR levels, we demonstrate that this pathway provides a critical escape mechanism from NAMPT inhibition. We show that NA restriction sensitizes AML to NAMPTis, significantly improving survival in vivo, identifying systemic NAD precursor metabolism as a key determinant of therapeutic efficacy.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Natori, Japan.",
    "Department of Biochemical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.",
    "Department of Respiratory Medicine, Miyagi Cancer Center Hospital, Natori, Japan.",
    "Multi Omics Platform, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.",
    "Human Biology-Microbiome-Quantum Research Center, Keio University, Tokyo, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kyoji Tsurumi",
      "orcid": "0009-0005-3363-424X"
    },
    {
      "affs": [
        0
      ],
      "name": "Miyuki Nomura",
      "orcid": "0000-0002-6168-6101"
    },
    {
      "affs": [
        0
      ],
      "name": "Mai Ohuchi",
      "orcid": "0009-0006-7330-6950"
    },
    {
      "affs": [
        3
      ],
      "name": "Ryoma Kizu",
      "orcid": "0009-0002-2073-555X"
    },
    {
      "affs": [
        0
      ],
      "name": "Naohiko Kikuchi",
      "orcid": "0009-0009-1786-4968"
    },
    {
      "affs": [
        0
      ],
      "name": "Taku Sato",
      "orcid": "0009-0005-5881-5354"
    },
    {
      "affs": [
        0
      ],
      "name": "Mami Morita",
      "orcid": "0009-0002-6471-6609"
    },
    {
      "affs": [
        0
      ],
      "name": "Yoji Yamashita",
      "orcid": "0009-0009-0998-4193"
    },
    {
      "affs": [
        0
      ],
      "name": "Kayoko Hayashi",
      "orcid": "0009-0004-2195-7319"
    },
    {
      "affs": [
        4
      ],
      "name": "Tomoyoshi Soga",
      "orcid": "0000-0001-9502-2509"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Yuki Sugiura",
      "orcid": "0000-0002-6983-8958"
    },
    {
      "affs": [
        2
      ],
      "name": "Tatsuro Fukuhara",
      "orcid": "0000-0003-0440-470X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nobuhiro Tanuma",
      "orcid": "0000-0001-7914-1380"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9gwv0w2me91y5.bib",
  "cited_by": 0,
  "doi": "10.1158/2767-9764.crc-26-0274",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13715585/",
  "id": "9gwv0w2me91y5",
  "issns": [
    "2767-9764"
  ],
  "landing_url": "https://doi.org/10.1158/2767-9764.crc-26-0274",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Diet"
    ],
    [
      "heading",
      "Leukemias"
    ],
    [
      "heading",
      "Lifestyle Risk Factors"
    ],
    [
      "heading",
      "Metabolic Pathways"
    ],
    [
      "heading",
      "Metabolism"
    ],
    [
      "heading",
      "Novel Mechanisms"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "heading",
      "Reversal Of Drug Resistance"
    ],
    [
      "openalex",
      "2717|Sirtuins and Resveratrol in Medicine"
    ]
  ],
  "openalex": "W7221549307",
  "pdf_url": "https://aacrjournals.org/cancerrescommun/article-pdf/doi/10.1158/2767-9764.CRC-26-0274/3838511/crc-26-0274.pdf",
  "pmcid": "PMC13715585",
  "pmid": "42862786",
  "published": "2026-10-28",
  "publisher": "American Association for Cancer Research",
  "ris": "https://research.draconitic.com/paper/9gwv0w2me91y5.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:51Z",
      "native_id": "PMC13715585",
      "source": "pmc",
      "url": "https://doi.org/10.1158/2767-9764.crc-26-0274"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "heading:Metabolism",
      "subfield": "enzymology-metabolism"
    }
  ],
  "title": "Nicotinic Acid Restriction Potentiates NAMPT Inhibition in Acute Myeloid Leukemia Xenograft Models",
  "title_text": "Nicotinic Acid Restriction Potentiates NAMPT Inhibition in Acute Myeloid Leukemia Xenograft Models",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:51Z",
  "url": "https://research.draconitic.com/paper/9gwv0w2me91y5",
  "venue": "Cancer Research Communications",
  "versions": []
}