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We previously showed that nicotinic acid riboside (NAR) sustains NAD biosynthesis in\u00a0vivo and compensates for NAMPT inhibition in SCLC models. Here, we evaluated combining NAMPT inhibition with dietary nicotinic acid (NA) restriction to suppress NAR\u2010dependent NAD biosynthesis. This combination showed enhanced antitumor activity consistent with synthetic lethality in SCLC CDX models and showed robust efficacy in PDX models, including those derived from chemotherapy\u2010refractory tumors. In most CDX models examined, combination therapy showed greater antitumor activity than standard chemotherapy with cisplatin and etoposide. Although we did observe transient leukopenia, the treatment was otherwise better tolerated than chemotherapy, with less impact on body weight and platelet counts. These findings support NAD metabolism\u2013targeted therapy as a promising strategy to treat SCLC.<\/jats:p>","DOI":"10.1111\/cas.70486","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:03:14Z","timestamp":1785283394000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nicotinic Acid Restriction Enhances the Therapeutic Benefit of\n                    <scp>NAMPT<\/scp>\n                    Inhibition in Small\u2010Cell Lung Cancer Models"],"prefix":"10.1111","author":[{"given":"Kyoji","family":"Tsurumi","sequence":"first","affiliation":[{"name":"Division of Cancer Chemotherapy Miyagi Cancer Center Research Institute  Natori Japan"},{"name":"Department of Biochemical Oncology Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Department of Respiratory Medicine Miyagi Cancer Center Hospital  Natori Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Nomura","sequence":"additional","affiliation":[{"name":"Division of Cancer Chemotherapy Miyagi Cancer Center Research Institute  Natori Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Ouchi","sequence":"additional","affiliation":[{"name":"Division of Cancer Chemotherapy Miyagi Cancer Center Research Institute  Natori Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1277-1203","authenticated-orcid":false,"given":"Shigehiro","family":"Yagishita","sequence":"additional","affiliation":[{"name":"Division of Molecular Pharmacology National Cancer Center Research Institute  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiko","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Division of Cancer Chemotherapy Miyagi Cancer Center Research Institute  Natori Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Cancer Chemotherapy Miyagi Cancer Center Research Institute  Natori Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Morita","sequence":"additional","affiliation":[{"name":"Division of Cancer Chemotherapy Miyagi Cancer Center Research Institute  Natori Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoji","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Division of Cancer Chemotherapy Miyagi Cancer Center Research Institute  Natori Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayoko","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Cancer Chemotherapy Miyagi Cancer Center Research Institute  Natori Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyoshi","family":"Soga","sequence":"additional","affiliation":[{"name":"Human Biology\u2010Microbiome\u2010Quantum Research Center Keio University  Tsuruoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinobu","family":"Hamada","sequence":"additional","affiliation":[{"name":"Division of Molecular Pharmacology National Cancer Center Research Institute  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Fukuhara","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Miyagi Cancer Center Hospital  Natori Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7914-1380","authenticated-orcid":false,"given":"Nobuhiro","family":"Tanuma","sequence":"additional","affiliation":[{"name":"Division of Cancer Chemotherapy Miyagi Cancer Center Research Institute  Natori Japan"},{"name":"Department of Biochemical Oncology Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nature14664","article-title":"Comprehensive Genomic Profiles of Small Cell Lung Cancer","volume":"524","author":"George J.","year":"2015","journal-title":"Nature"},{"key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-020-00235-0","article-title":"Small\u2010Cell Lung Cancer","volume":"7","author":"Rudin C. 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