Role of pathway choice for DNA double-strand break repair in cancer radiotherapy

• Project/Area Number: 17H04263
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Osaka University
• Principal Investigator: Seo Yuji 大阪大学, 医学系研究科, 助教 (00302000)
• Co-Investigator(Kenkyū-buntansha): 小川 和彦 大阪大学, 医学系研究科, 教授 (40253984)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000); Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 放射線治療 / DNA2本鎖切断修復 / 放射線 / 癌 / 放射線感受性 / がん / DNA修復

Outline of Final Research Achievements

There are at least four mechanisms to repair DNA double-strand breaks (dsbs). Poly(ADP-ribose) polymerase inhibitors suppressed repair of DNA dsbs by a homologous recombination repair and a microhomology-mediated end joining, while increasing repair through a single-strand annealing pathway. The altered choice of the repair mechanism for ionizing radiation-induced DNA dsbs increased the formation of chromosomal translocations. The findings suggested that adjusting the choice of the repair pathways may enhance the efficacy of radiotherapy and reduce potential adverse effects.

Academic Significance and Societal Importance of the Research Achievements

放射線照射によるDNA損傷に対して複数の修復機構がどのように選択され、それぞれ修復結果がどのように異なるのか。またそれらが癌細胞の放射線感受性にどう影響するのか。これらを明らかにすることで、がん放射線治療の効果を予測したり、効果を増強させる方策の開発につながる可能性がある。また放射線照射の副作用として遺伝子異常が生じることを軽減させる方法の開発につながることが期待される。

Research Products

• [Journal Article] Impact of accumulated alterations in driver and passenger genes on response to radiation therapy (2020)
  • Author(s): Seo Yuji、Tamari Keisuke、Takahashi Yutaka、Minami Kazumasa、Isohashi Fumiaki、Suzuki Osamu、Sumida Iori、Ogawa Kazuhiko
  • Journal Title: The British Journal of Radiology Volume: - Issue: 1109 Pages: 20190625-20190625
  • DOI: 10.1259/bjr.20190625
  • Peer Reviewed
• [Journal Article] Ro 90-7501 Is a Novel Radiosensitizer for Cervical Cancer Cells that Inhibits ATM Phosphorylation (2019)
  • Author(s): TAMARI KEISUKE、SANO KEISUKE、LI ZHIHAO、SEO YUJI、OTANI KEISUKE、TATEKAWA SHOTARO、TORATANI MASAYASU、TAKAOKA YUJI、TAKAHASHI YUTAKA、MINAMI KAZUMASA、ISOHASHI FUMIAKI、KOIZUMI MASAHIKO、OGAWA KAZUHIKO
  • Journal Title: Anticancer Research Volume: 39 Issue: 9 Pages: 4805-4810
  • DOI: 10.21873/anticanres.13665
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 11C-methionine-18F-FDG dual-PET-tracer-based target delineation of malignant glioma: evaluation of its geometrical and clinical features for planning radiation therapy. (2018)
  • Author(s): Hirata T, Kinoshita M, Tamari, Seo Y, Suzuki O, Wakai N, Achiha T, Umehara T, Arita H, Kagawa N, Kanemura Y, Shimosegawa E, Hashimoto N, Hatazawa J, Kishima H, Teshima T, Ogawa K.
  • Journal Title: Journal of Neurosurgery Volume: 21 Issue: 3 Pages: 1-11
  • DOI: 10.3171/2018.4.jns1859
  • Peer Reviewed / Open Access
• [Journal Article] Radiobiological effects of flattening filter?free photon beams on A549 non-small-cell lung cancer cells (2018)
  • Author(s): Nakano Hisashi、Minami Kazumasa、Yagi Masashi、Imaizumi Hiromasa、Otani Yuki、Inoue Shinichi、Takashina Masaaki、Seo Yuji、Takahashi Yutaka、Sumida Iori、Ogawa Kazuhiko、Koizumi Masahiko
  • Journal Title: Journal of Radiation Research Volume: 59 Issue: 4 Pages: 442-445
  • DOI: 10.1093/jrr/rry041
  • Peer Reviewed / Open Access
• [Journal Article] The effect of beam shape on physical parameters of head and neck simultaneous-integrated boost intensity-modulated radiation therapy (2018)
  • Author(s): Tsubouchi Toshiro、Yagi Masashi、Sumida Iori、Tamari Keisuke、Seo Yuji、Ogawa Kazuhiko
  • Journal Title: Reports of Practical Oncology & Radiotherapy Volume: 23 Issue: 5 Pages: 425-432
  • DOI: 10.1016/j.rpor.2018.08.008
• [Journal Article] Carbon ion irradiation enhances the antitumor efficacy of dual immune checkpoint blockade therapy both for local and distant sites in murine osteosarcoma (2018)
  • Author(s): Takahashi Yutaka、Yasui Tomohiro、Minami Kazumasa、Tamari Keisuke、Hayashi Kazuhiko、Otani Keisuke、Seo Yuji、Isohashi Fumiaki、Koizumi Masahiko、Ogawa Kazuhiko
  • Journal Title: Oncotarget Volume: 10 Issue: 6 Pages: 9364-9378
  • DOI: 10.18632/oncotarget.26551
  • Peer Reviewed / Open Access
• [Presentation] A dual role of genomic instability on radiosensitivity in cancer cells (2019)
  • Author(s): Y. Seo, K. Tamari, Y. Takahashi, K. Minami, K. Otani, F. Isohashi, K. Ogawa
  • Organizer: American Association for Cancer Research Annual Meeting 2019
  • Int'l Joint Research
• [Book] 放射線治療学 (2017)
  • Author(s): 井上俊彦、小川和彦、小泉雅彦
  • Total Pages: 439
  • Publisher: 南山堂
  • ISBN: 9784525270964