| Project/Area Number |
18K15965
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Miyagi Prefectural Hospital Organization Miyagi Cancer Center |
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Principal Investigator |
Morita Mami 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (20647193)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 小細胞肺がん / 代謝 / Pkm1 / Pkm2 / Pkm / 肺神経内分泌腫瘍 / 前臨床 |
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| Outline of Final Research Achievements |
Small-cell lung cancer (SCLC) accounts for about 15% of human lung cancers, and patient prognosis in these cases is poorer than that of patients with other lung cancers. Although recent genomic studies show simultaneous bi-allelic inactivation of TP53 and RB1 in human SCLC, these studies reveal few driver mutations in SCLC that could be therapeutically targeted.
In this study, we tried to develop a novel strategy to treat SCLC by targeting their metabolic vulnerability. We found that SCLC survival and/or proliferation are highly dependent on the NAD biosynthesis, hence vulnerable upon inhibition of the pathway. We have (1) validated the efficacy of the NAD-targeting therapy in mouse preclinical models, (2) evaluated the molecular details of SCLC metabolic vulnerability, (3) evaluated SCLC dependency to three NAD precursors in culture.
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| Academic Significance and Societal Importance of the Research Achievements |
小細胞肺がんの代謝ターゲット治療の有用性を、マウス前臨床モデルにて示した。肺がんの～15%を占める肺神経内分泌腫瘍（小細胞肺がんを含む）においては、腺癌の場合のような明確で標的化が可能なドライバー変異が存在しない。故に、これら難治肺がんに対しては、ドライバー変異以外の要素を創薬開発する戦略が求められている。これらの肺がんは、発見時には外科的治療のタイミングを逸していることが多く、その文脈でも、新たな分子標的治療を開発する意義は大きい。
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