Development of novel molecular targeted therapies, inducing apoptotic cell death, in endometrial and ovarican carcinomas

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462515
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: Oda Katsutoshi 東京大学, 医学部附属病院, 准教授 (30359608)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 子宮体癌 / 卵巣癌 / 分子標的治療 / ゲノム解析 / バイオマーカー / PI3K / MDM2 / TP53

Outline of Final Research Achievements

We identified molecular subtypes and candidate molecular-targeted therapies in endometrial and ovarian (mainly clear cell histology) cancers. Furthermore, we revealed their anti-tumor effects in these cancers.
1. We found that either a MAPK inhibitor or ionizing radiation synergistically enhanced anti-tumor effect by a PI3K pathway inhibitor (dual PI3K/mTOR inhibitor) in endometrial cancer cells. We showed that HIF-1alpha/VEGF pathway plays an essential role in the cell proliferation of endometrial cancer cells and that HIF-1alpha/VEGF activity is dependent on activation of the PI3K/mTOR pathway.
2. We revealed a poor prognostic subgroup in ovarian clear cell carcinomas, using genome-wide analyses, including single nucleotide polymorphism arrays and expression arrays. We reported that over-expression of MDM2 is associated with poor prognosis and that inhibiting MDM2 showed anti-tumor effect in ovarian clear cell carcinoma cells.

Free Research Field

婦人科腫瘍学