Elucidation of regulated mechanism in controlling purine metabolism through PI3K/mTOR pathway in small cell lung cancer
| Project/Area Number |
17K07189
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Makinoshima Hideki 国立研究開発法人国立がん研究センター, 先端医療開発センター, ユニット長 (30510573)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 肺小細胞がん / PI3K/mTOT経路 / プリンヌクレオチド / 核酸代謝 / PI3K/mTOR経路 / プリン塩基 / 癌 |
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| Outline of Final Research Achievements |
To elucidate the metabolic pathway by which PI3K/mTOR regulates purine biosynthesis in small-cell lung carcinoma cell (SCLC), we conducted this research. I almost achieved the initially planned goals. There are two types of purine nucleotide biosynthesis pathways, a de novo pathway and a salvage pathway. The PI3K/mTOR pathway positively regulates the new synthesis pathway, and it seems that the SCLC cell lines which have high salvage pathway activity seems to be resistant to PI3K/mTOR inhibitors. The important outcome of this research is establishment of a defective SCLC cell line of HPRT1 gene, which is an enzyme that exists in the purine nucleotide recycling pathway. Moreover, it is the construction of an experimental system for measuring the biosynthesis ratio derived from either de novo or salvage route using SCLC cells. It is expected that these research results will be useful for research on SCLC.
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| Academic Significance and Societal Importance of the Research Achievements |
肺小細胞がんは、肺がんの15％程度の症例数であるが、進行が速く、治療抵抗性が臨床上問題となっている。近年新たな治療法が開発されず、新規の治療標的の同定が必要である。本研究では、PI3K/mTOR阻害剤の感受性と代謝産物のプロファイルを解析し、PI3K/mTOR阻害剤の臨床研究と並行し、代謝産物由来のバイオマーカー探索も行った。今後、新規治療法の開発に発展する研究が期待できる。さらに、この科研費を用いたことが記載されている論文が少なくとも3報発表することができ、社会的な意義も大きかったと感じている。
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Metabolic Characterization of Antifolate Responsiveness and Non-responsiveness in Malignant Pleural Mesothelioma Cells.2018
Author(s)
Sato Y, Matsuda S, Maruyama A, Nakayama J, Miyashita T, Udagawa H, Umemura S, Yanagihara K, Ochiai A, Tomita M, Soga T, Tsuchihara K, Makinoshima H.
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Journal Title
Front Pharmacol.
Volume: 9
Pages: 1129-1129
Related Report
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[Journal Article] Metabolic Determinants of Sensitivity to Phosphatidylinositol 3-Kinase Pathway Inhibitor in Small-Cell Lung Carcinoma.2018
Author(s)
Makinoshima H, Umemura S, Suzuki A, Nakanishi H, Maruyama A, Udagawa H, Mimaki S, Matsumoto S, Niho S, Ishii G, Tsuboi M, Ochiai A, Esumi H, Sasaki T, Goto K, Tsuchihara K.
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Journal Title
Cancer Res.
Volume: 78
Pages: 2179-2190
Related Report
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