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2013 Fiscal Year Final Research Report

Potential role of mTORC2 as a therapeutic target in epithelial ovarian cancer

Research Project

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Project/Area Number 23592446
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionOsaka University

Principal Investigator

MABUCHI Seiji  大阪大学, 医学(系)研究科(研究院), 助教 (00452441)

Co-Investigator(Kenkyū-buntansha) SAWADA Kenjiro  大阪大学, 医学系研究科, 講師 (00452392)
SOBE I Aki  大阪大学, 医学系研究科, 助教 (60397619)
HASHIMOTO Kae  大阪大学, 医学系研究科, 助教 (90612078)
Project Period (FY) 2011 – 2013
KeywordsmTORC2 / mTORC1 / mTORC1阻害薬 / 耐性化 / Trabectedin
Research Abstract

In the current study, we found that mTORC2 is frequently activated in ovarian cancer, especially in clear cell carcinoma of the ovary (CCC). mTORC2 stimulated cell proliferation and mediate the acquired resistance to mTORC1 inhibitor (Mol Cancer Ther. 2013;12:1367-77.). We also identified trabectedin shows significant antitumor activity toward chemosensitive and chemoresistant CCC cells. The inhibition of mTORC1 significantly enhanced the therapeutic efficacy of trabectedin and prevented CCC cells from acquiring resistance to trabectedin. Finally, we found that treatment with trabectedin plus irinotecan in combination with mTOR inhibitors displays the strong anti-tumor effect against ovarian CCC (Clin Cancer Res 2011;17:4462-73., Int J Gynecol Cancer 2014, in press). Our studies provide the rationale for future clinical trials of mTOR targeting therapies in combination with trabectedin in patients with ovarian CCC.

  • Research Products

    (4 results)

All 2013 2012 2011

All Journal Article (3 results) Presentation (1 results)

  • [Journal Article] Potential Role of mTORC2 as a Therapeutic Target in Clear Cell Carcinoma of the Ovary2013

    • Author(s)
      Hisamatsu T, Mabuchi S, Matsumoto Y, Kawano M, Sasano T, Takahashi R, Sawada K, Ito K, Kurachi H, Schilder RJ, Testa JR, Kimura T
    • Journal Title

      Mol Cancer Ther

      Volume: 12 Pages: 1367-77

  • [Journal Article] Targeting mTOR signaling pathway in ovarian cancer2011

    • Author(s)
      Mabuchi S, Hisamatsu T, Kimura T
    • Journal Title

      Curr Med Chem

      Volume: 18 Pages: 2960-8

  • [Journal Article] The activity of trabectedin as a single agent or in combination with everolimus for clear cell carcinoma of the ovary2011

    • Author(s)
      Mabuchi S, Hisamatsu T, Kawase C, Hayashi M, Sawada K, Mimura K, Takahashi K, Takahashi T, Kurachi H, Kimura T
    • Journal Title

      Clin Cancer Res

      Volume: 17 Pages: 4462-73

  • [Presentation] What's clear and not clear about clear cell cancer2012

    • Author(s)
      Seiji Mabuchi
    • Organizer
      14^<th> Biennial meeting of International Gynecologic Cancer Society
    • Place of Presentation
      Vancouver Canada
    • Year and Date
      20121013-16

URL: 

Published: 2015-07-16  

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