Drug screening and identification of biomarkers using sensitivity assay with a panel of primary cultured cancer spheroids derived from endometrial cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462522
• 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: Yoshino Kiyoshi 大阪大学, 医学系研究科, 准教授 (90362730)
• Co-Investigator(Renkei-kenkyūsha): INOUE Masahiro 大阪府立成人病センター研究所, 生化学部門, 部長 (10342990) ; NAKA Tetsuji 医薬基盤研究所, 免疫シグナルプロジェクト, プロジェクトリーダー (30303936)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 婦人科腫瘍 / 子宮体癌 / CTOS / 播種 / バイオマーカー / YM155

Outline of Final Research Achievements

We successfully prepared and cultured cancer tissue-originated spheroids
(CTOS) from endometrial cancers. Then, we screened 79 molecular targeting drugs using two CTOSs. Among several hits, we focused on everolimus and YM155, a survivin inhibitor. When sensitivity to everolimus or YM155 was assessed in 12 CTOSs, the sensitivity varied substantially. The phosphorylation status of the mammalian target of rapamycin complex 1 downstream molecules before and after everolimus treatment did not predict the effect of the drug. In contrast, the CTOS sensitive to YM155 showed remarkable cell death. The effect of YM155 was also confirmed in vivo. The histological type correlated with YM155 sensitivity; non-endometrioid adenocarcinomas were sensitive and endometrioid adenocarcinomas were resistant. Thus, sensitivity assays using cancer tissue-originated spheroids from endometrial cancers may be useful for screening drugs and finding biomarkers.

Free Research Field

婦人科腫瘍