| Project/Area Number |
17K16828
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Akiyama Azusa 筑波大学, 医学医療系, 講師 (80647272)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
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)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 子宮頸癌 / 化学放射線療法 / PIK3CA遺伝子変異 / シスプラチン / PIK3CA遺伝子 / シスプラチン併用同時化学放射線療法 / PI3-kinase/Aktシグナル伝達経路 / 腫瘍学 / 分子標的治療薬 |
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| Outline of Final Research Achievements |
The activated PI3-kinase/Akt pathway is known to be involved in both cisplatin-resistance and radioresistance, to date, only a few studies have reported significant associations between PIK3CA gene mutational status and outcome by CCRT in the disease. The aim of this study was to clarify the prognostic significance of PIK3CA mutational status in cervical cancers treated by CCRT.PIK3CA mutation was found in 7 of 59 patients (12%). Subsequent survival analyses revealed that PIK3CA mutation was a significant prognostic factor for poor overall survival [multivariate adjusted HR, 3.9; 95% CI, 1.3-11.8; P＝.017] and cancer-specific survival (multivariate adjusted HR, 3.6; 95% CI, 1.2-11.0; P＝.024).
Molecular inhibitors targeting the PI3-kinase/Akt pathway may improve the outcome by CCRT in cervical cancers harboring PIK3CA mutation, providing significant implications for novel treatment strategy based on precision medicine in the disease.
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| Academic Significance and Societal Importance of the Research Achievements |
進行子宮頸癌においてPIK3CA遺伝子変異を12％に認めた。子宮頸癌におけるPIK3CA遺伝子変異は有意な予後不良因子であることを示した。
PIK3CA遺伝子変異によるPI3K/Akt経路の活性化のために放射線感受性およびシスプラチン感受性が減少し、CCRTの効果が減弱し予後が不良となるのであれば、PI3K/Aktシグナル経路をターゲットとした分子標的治療薬は、PI3KCA遺伝子変異を有する進行子宮頸癌において予後を改善できる可能性がある。
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