Development of chemoprevention for familial breast cancer focusing on the cancer metabolism
| Project/Area Number |
16K15378
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hygiene and public health
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Watanabe Motoki 京都府立医科大学, 医学(系)研究科(研究院), 講師 (40723581)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | HDAC阻害剤 / vorinostat / salazosulfapyridine / グルタチオン代謝 / MEK阻害剤 / statins / メバロン酸代謝 / トリプルネガティブ乳癌 / sulfasalazine / スタチン / 癌代謝 / グルタチオン代謝経路 / メバロン酸代謝経路 / サラゾピリン / 分子標的癌予防 |
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| Outline of Final Research Achievements |
We investigated whether the combination of molecular-targeting agents against the abnormalities of cancer-related genes with the inhibitors of cancer-related metabolism could be a feasible strategy for the chemoprevention of the familial breast cancer. We thus tried two combination therapies as follows: (1) HDAC inhibitor vorinostat and the inhibitor of the glutathione pathway, salazosulfapyridine (2) MEK inhibitors and the inhibitor of the mevalonate pathway, statins. We here found that both combinations inhibited the cell growth with the induction of cell death in several cancer cell lines, including breast cancer, indicating that our concept may be applied to the prevention or treatment against various types of cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、網羅的遺伝子解析の実用化に伴い、がん予防の分野においても、個人個人の遺伝的背景に応じた発がん予防を目指した『先制医療』の考え方が注目されている。我々は今回、こうしたがんゲノム医療全盛の時代に、がんゲノムのみを標的とする医療は不十分で、がん細胞の代謝環境にも注目する重要性を明らかにし、実際、「分子標的薬と代謝制御薬の併用戦略」として、２つのモデル（HDAC阻害剤とグルタチオン代謝制御／MEK阻害剤とメバロン酸代謝制御）を提案した。本研究をさらに発展させることにより、がん予防効果を最大限に発揮する『ゲノムと代謝の双方を標的とした新時代のがん先制医療の実現』に貢献できることが期待される。
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Report
(3 results)
Research Products
(3 results)
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[Journal Article] Blockage of the mevalonate pathway overcomes the apoptotic resistance to MEK inhibitors with suppressing the activation of Akt in cancer cells.2018
Author(s)
Iizuka-Ohashi M1,2, Watanabe M1, Sukeno M1, Morita M1, Hoang NTH3, Kuchimaru T, Kizaka-Kondoh S, Sowa Y1 Sakaguchi K, Taguchi T, Sakai T.
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Journal Title
Oncotarget.
Volume: 9
Issue: 28
Pages: 19597-19612
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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