The molecular mechanism underlying how cancer cells acquire resistance to anti-tumor drugs through mTORC1-mediated regulation of mRNA translation
| Project/Area Number |
18K07237
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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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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Morita Masahiro 熊本大学, 生命資源研究・支援センター, 客員准教授 (50549475)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 抗がん剤 / 抵抗性 / mRNA翻訳 / 代謝リプログラミング / mTOR阻害剤 / ミトコンドリア / 肝臓がん / mTORC1シグナル / がん / mTOR / mRNA translation / Drug resistance |
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| Outline of Final Research Achievements |
Current cancer therapies targeting key components of the signaling pathways fail due mostly to the emergence of mutations or activation of compensatory signaling pathways that render these drugs ineffective. Indeed, many patients display resistance to the anti-tumor drugs by activating alternative cancer-promoting pathways. The goal of my research project is to identify alternative cancer-promoting pathways that enable cancer cells resistant to anti-tumor drugs. My research demonstrated that a combination of anti-tumor drugs with chemical inhibitors targeting mRNA translational mechanisms greatly improves its therapeutic benefits for cancer that eventually becomes resistant to treatment. Overall, the proposed research program showed a strong potential to deliver a new generation of therapeutic regimens to the population of the nation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題では、がん細胞がどのように抗がん剤への抵抗性を獲得するかの分子機構の一端を示すことができた。タンパク質合成やミトコンドリアの活性を抑制する化合物を抗ガン剤と併用することによって抵抗性獲得の分子機構を抑制することにより、その抗腫瘍効果を増強することができた。以上の結果により、抗がん剤治療において新たな治療戦略を提唱することができた。
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Hepatic posttranscriptional network comprised of CCR4?NOT deadenylase and FGF21 maintains systemic metabolic homeostasis2019
Author(s)
*M. Morita, N. Siddiqui, S. Katsumura, C. Rouya, O. Larsson, T. Nagashima, B. Hekmatnejad, A. Takahashi, H. Kiyonari, M. Zang, R. St-Arnaud, V. Giguere, I. Topisirovic, M. Okada-Hatakeyama, T. Yamamoto, N. Sonenberg
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Journal Title
Proceedings of the National Academy of Sciences
Volume: 116
Issue: 16
Pages: 7973-7981
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Translational and HIF-1α-Dependent Metabolic Reprogramming Underpin Metabolic Plasticity and Responses to Kinase Inhibitors and Biguanides2018
Author(s)
2.*L. Hulea, *S.P. Gravel, *M. Morita, M. Cargnello, O. Uchenunu, Y.K. Im, C. Lehuédé, E.H. Ma, M. Leibovitch, S. McLaughlan, M.J. Blouin, M. Parisotto, V. Papavasiliou, C. Lavoie, O. Larsson, M. Ohh, et al., P. Siegel, R.G. Jones, W. Muller, J. Ursini-Siegel, J. St-Pierre, M. Pollak, I. Topisirovic
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Journal Title
Cell Metabolism
Volume: 28
Issue: 6
Pages: 817-832.e8
DOI
NAID
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Translational control of ERK signaling through miRNA/4EHP-directed silencing2018
Author(s)
3.S.M. Jafarnejad, C. Chapat, E. Matta-Camacho, I.A. Gelbart, G.G. Hesketh, M. Arguello, A. Garzia, S.H. Kim, J. Attig, M. Shapiro, M. Morita, A. Khoutorsky, T. Alain, C. Gkogkas, N. Stern-Ginossar, T. Tuschl, A.C. Gingras, T.F. Duchaine, N. Sonenberg
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Journal Title
eLife
Volume: 7
Pages: 35034-35034
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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