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2022 Fiscal Year Final Research Report

Escape from energy/NAD-interdependence in malignant cancers

Research Project

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Project/Area Number 21K19420
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 50:Oncology and related fields
Research InstitutionMiyagi Prefectural Hospital Organization Miyagi Cancer Center

Principal Investigator

Tanuma Nobuhiro  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, 部長 (40333645)

Project Period (FY) 2021-07-09 – 2023-03-31
Keywords代謝 / がん / NAD / 解糖系
Outline of Final Research Achievements

Small cell lung cancer (SCLC) is significantly vulnerable to inhibition of NAD synthesis, while other cancer types, including non-small cell lung cancer (NSCLC), are less sensitive. To understand the mechanism of such difference, we analyzed the metabolism of cells treated with inhibitors of the NAD salvage pathway where NAPMT is a rate-limiting. We found that SCLC depends on GAPDH in glycolysis to maintain its energy state, whereas NSCLC can maintain those even under GAPDH inactivation. The GAPDH-independent energy homeostasis may contribute to resistance to NAD biosynthesis inhibition in NSCLC.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

様々ながんの代謝特性が明らかになるにつれ、一部のがんに特徴的な代謝特性が存在することが分かってきた。本課題で取り組んだ、SCLCのNAD依存もその1つである、このような性質は、ターゲットする手段さえ開発できれば、がんの新たな治療標的となる可能性がある。本研究では、SCLCのNAD依存メカニズムの一端を明らかにした。SCLCに対する新たな代謝ターゲット治療の開発に向けて、その理論根拠を得ることができた。

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Published: 2024-01-30  

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