2015 Fiscal Year Final Research Report
Development of combination therapy using PI3K inhibitor and its predictive biomarker in clear cell carcinoma of the ovary
Project/Area Number |
25462594
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Tottori University |
Principal Investigator |
Oishi Tetsuro 鳥取大学, 医学部附属病院, 講師 (80359877)
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Co-Investigator(Kenkyū-buntansha) |
ITAMOCHI Hiroaki 岩手医科大学, 医学部, 教授 (20314601)
SHIMADA Muneaki 鳥取大学, 医学部, 講師 (40362892)
SATO Syinya 鳥取大学, 医学部附属病院, 講師 (10423261)
CHIKUMI Jun 鳥取大学, 医学部附属病院, 医員 (70467702)
SATO Seiya 岩手医科大学, 医学部, 助教 (30621007)
HARADA Tasuku 鳥取大学, 医学部, 教授 (40218649)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Keywords | 卵巣癌 / 明細胞腺癌 / PI3K |
Outline of Final Research Achievements |
We investigated PI3K-Akt-mTOR pathway molecules and ARID1A expression in clear cell carcinoma of the ovary (CCC), which is known to be resistant to standard chemotherapy. The study using tumor tissue specimens indicated that PIK3CA mutant cases showed significantly worse overall survival than wild-type cases. The 5-year survival rate for FIGO stage I or II patients with negative tumor expression of ARID1A was lower than those with positive tumor expression of ARID1A. Multivariable analysis revealed that ARID1A expression was an independent prognostic factor in stage I or II CCC patients. In vitro study revealed that treatment with the PI3K/mTOR dual inhibitor NVP-BEZ235 suppressed p-Akt expression and cell proliferation in CCC cells. BEZ235 significantly inhibited tumor growth in mice bearing OVISE and TU-OC-1 cell tumors.
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Free Research Field |
婦人科腫瘍学
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