Basic research to explore factors to improve effectiveness of radiation therapy

2015 Fiscal Year Final Research Report

• Project/Area Number: 24249067
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: OKAYASU RYUICHI 国立研究開発法人放射線医学総合研究所, 放射線防護研究センター, 主任研究員 (50356135)
• Co-Investigator(Renkei-kenkyūsha): FUJIMORI Akira 放射線医学総合研究所, チームリーダー (50314183) ; SAI Sei 放射線医学総合研究所, 主任研究員 (20342735) ; YAJIMA Hirohiko 放射線医学総合研究所, 主任研究員 (30261895)
• Research Collaborator: JEGGO Penny ; NICKOLOFF Jac ; Lee Younghyun ; 正岡 綾 ; 砂田 成章 ; 平川 博一 ; Li Huizi
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: Hsp90阻害剤 / 重粒子線 / 放射線増感 / TAS-116 / DNA二重鎖切断修復 / DNA-PK阻害剤 / 細胞周期 / 細胞老化

Outline of Final Research Achievements

In order to improve the world leading heavy ion radiotherapy, we studied the combination regimen of Hsp90 inhibitor and carbon-ion irradiation. After screening and studying various inhibitors, we found that most Hsp90 inhibitors can cause tumor specific radio-sensitization with heavy ions and the cause of this was shown to be inhibition of DNA double strand break (DSB) repair by the inhibitors. Among these we suggest that an Hsp90 inhibitor TAS-116 might be most recommendable clinically due to its low toxicity.
We also studied the combination effects of a DNA DSB repair inhibitor NU7441 and radiation including heavy ions. Our investigation indicated that a non-toxic concentration of NU7441 radio-sensitized tumor cells and the cause seems to be related to disturbed cell cycle progression. Moreover, some tumor cells show senescence like appearance after the combination treatment. Our study forms a biological basis for a new combination cancer therapy including particle radiation.

Free Research Field

放射線治療生物学