Radiosensitization

• Project/Area Number: 24791293
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Kyoto University
• Principal Investigator: YOSHIMURA MICHIO 京都大学, 医学(系)研究科(研究院), 助教 (40597936)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 放射線増感 / 分子標的薬 / 放射線治療 / 細胞周期 / 放射線 / 分子標的 / 放射線増感剤

Outline of Final Research Achievements

Polo-like kinase 1 is a serine/threonine kinase that functions in mitotic progression. We herein investigated whether PLK1 blockade enhanced the cytotoxic effects of radiation by modulating the cell cycle phase of cancer cells using the novel small molecule inhibitor of PLK1, TAK-960. In vitro clonogenic assays as well as time-lapse imaging and flow cytometric analyses of cell cycle phases demonstrated that the TAK-960 treatment exhibited a radiosensitizing effect, especially when it increased the proportion of M-phase cells. Tumor growth delay assay combined with optical imaging of cell cycle phases in tumor xenografts also demonstrated that the radiosensitizing effect of TAK-960 depended on an increase in the proportion of M-phase cells. These results provide a rational basis of targeting PLK1 for radiosensitization when considering the therapeutic time window for M-phase arrest as the best timing for radiation treatment.

Research Products

• [Journal Article] Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer : Prolonged disease-free interval associated with favorable prognosis (2014)
  • Author(s): Nakamura, A. Itasaka S, Takaori K, Kawaguchi Y, Shibuya K, Yoshimura M, Matsuo Y, Mizowaki T, Uemoto S, Hiraoka M.
  • Journal Title: Strahlentherapie und Onkologie Volume: MAR 6 Issue: 5 Pages: 485-485
  • DOI: 10.1007/s00066-014-0610-8
  • Peer Reviewed
• [Journal Article] Factors influencing survival outcome for radiotherapy for biliary tract cancer: A multicenter retrospective study (2014)
  • Author(s): Yoshioka, Y. Ogawa K, Yoshimura M et al.
  • Journal Title: Radiotherapy and oncology Volume: Feb 20 Issue: 3 Pages: 2167-2167
  • DOI: 10.1016/j.radonc.2014.01.003
  • Peer Reviewed
• [Journal Article] HIF-1-mediated metabolic reprogramming reduces ROS levels and facilitates the metastatic colonization of cancers in lungs. (2014)
  • Author(s): 1. Zhao T, Zhu Y, Morinibu A, Kobayashi M, Shinomiya K, Itasaka S, Yoshimura M, Guo G, Hiraoka M, Harada H.
  • Journal Title: Scientific Reports Volume: 4.3793 Issue: 1 Pages: 1-7
  • DOI: 10.1038/srep03793
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of decreased hypoxia-inducible factor 1 activity and resultant G(1)-S cell cycle transition in radioresistance of perinecrotic tumor cells (2013)
  • Author(s): Y. Zhu, T. Zhao, S. Itasaka, L. Zeng, C.J. Yeom, K. Hirota, K. Suzuki, A. Morinibu, K. Shinomiya, G. Ou, M. Yoshimura, M. Hiraoka, H. Harada
  • Journal Title: Oncogene Volume: 32 Issue: 16 Pages: 2058-2068
  • DOI: 10.1038/onc.2012.223
  • Peer Reviewed
• [Journal Article] Microenvironment and radiation therapy (2013)
  • Author(s): M Yoshimura, S Itasaka, H Harada,
  • Journal Title: Biomed Res Int Volume: 2013 Pages: 685308-685308
  • DOI: 10.1155/2013/685308
  • NAID: 120005243745
  • Peer Reviewed
• [Journal Article] Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels (2012)
  • Author(s): H. Harada, M. Inoue, S. Itasaka, K. Hirota,A. Morinibu, K. Shinomiya, L. Zeng, G. Ou, Y. Zhu, M. Yoshimura, W.G. McKenna, R.J. Muschel, M. Hiraoka
  • Journal Title: Nature communications Volume: 3 Issue: 1 Pages: 783-783
  • DOI: 10.1038/ncomms1786
  • NAID: 120004007582
  • Peer Reviewed
• [Presentation] PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase (2015)
  • Author(s): 井上実, 吉村通央, 小林稔, 板坂聡, 本田弘平,原田浩, 平岡真寛
  • Organizer: 第17回癌治療増感研究シンポジウム
  • Place of Presentation: 奈良
  • Year and Date: 2015-02-06 – 2015-02-07
• [Presentation] A PLK1 inhibitor, TAK-960, acts as a radiosensitizer by inducing mitotic arrest (2014)
  • Author(s): 井上実, 吉村通央, 小林稔, 板坂聡, 本田弘平,原田浩, 平岡真寛
  • Organizer: 日本放射線腫瘍学会第27回学術大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-12-11 – 2014-12-13
• [Presentation] A novel small molecule inhibitor of PLK1, TAK-960, sensitizes therapeutic effect of radiation by inducing mitotic arrest (2014)
  • Author(s): 井上実, 吉村通央, 小林稔, 板坂聡, 本田弘平,原田浩, 平岡真寛
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Book] Principles of Molecular Diagnostics and Personalized Cancer Medicine (2012)
  • Author(s): Dongfeng Tan, Henry T. Lynch, Yoshimura, M. Harada, H. Hiraoka, M.
  • Total Pages: 992
  • Publisher: Lippincott Williams & Wilkins