Novel approaches to cancer treatment based on DNA damage and tumor immunity activation induced by proton beam irradiation

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390287
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: University of Tsukuba
• Principal Investigator: TSUBOI Koji 筑波大学, 医学医療系, 教授 (90188615)
• Co-Investigator(Kenkyū-buntansha): SAKAE Takeji 筑波大学, 医学医療系, 教授 (60162278) ; KUMADA Hiroaki 筑波大学, 医学医療系, 准教授 (30354913) ; MORITAKE Takashi 筑波大学, 医学医療系, 講師 (50450432) ; HASHIMOTO Takayuki 筑波大学, 医学医療系, 講師 (60400678) ; SUZUKI Kenshi 筑波大学, 医学医療系, 助教 (20726442)
• Co-Investigator(Renkei-kenkyūsha): ITO Atsuo 産業技術総合研究所, ヒューマンライフテクノロジー研究部門, グループリーダー (30356480) ; OHNO Tadao 日本歯科大学, 生命歯学部, 客員教授 (90160580)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: がん / 陽子線治療 / DNA損傷 / 化学療法 / 腫瘍免疫

Outline of Final Research Achievements

1) The “complex DNA damages” induced by irradiation make a significant impact on cell inactivation or transformation. Although complex DNA damage formation was dependent on radiation quality in the early phase after irradiation, senescence-like growth arrest was suggested to be the major cellular response in the later phase, regardless of radiation quality.
2) A selective Cox-2 inhibitor “celecoxib” sensitized malignant brain tumor cells to gamma-rays by loading ER stress. The major modality of cell death induced was autophagy, suggesting that celecoxib is a promising candidate for radosensitizing refractory malignant brain tumors.
3) Local cancer radiotherapy may have an effect as an immune adjuvant. We found that a tumor-specific immune system was activated when the primary tumor was cured by irradiation. This “abscopal effect” was effective even in the brain. In contrast, primary tumor recurrence after irradiation resulted in suppression of tumor immunity.

Free Research Field

放射線生物学