| Project/Area Number |
23592446
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Osaka 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
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | mTORC2 / mTORC1 / mTORC1阻害薬 / 耐性化 / Trabectedin / 耐性化機構 / 卵巣癌 / 明細胞腺癌 / 卵巣明細胞腺癌 / everolimus |
|---|
| 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.
|
