Radiosensitization with molecular targeted drugs in pancreatic cancer therapy : analysis by tumor imaging

2009 Fiscal Year Final Research Report

• Project/Area Number: 20790892
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Kyoto University
• Principal Investigator: ITASAKA Satoshi Kyoto University -> 京都大学, 医学研究科, 助教 (90378654)
• Project Period (FY): 2008 – 2009
• Keywords: 膵癌 / 放射線 / 分子標的 / イメージング / 低酸素

Research Abstract

Purpose of this study is to enhance the effects of irradiation on pancreatic cancer with molecular targeted drugs. We evaluated the treatment effects of radiation with anti-VEGF antibody and the change of HIF-1 activity by imaging. We confirmed that irradiation at the timing of low HIF-1 activity is correlated with enhanced irradiation effects. In contrast, when irradiation was given at the timing of high HIF-1 activity, anti-tumor effects of irradiation was decreased. We also revealed that newly developed hypoxia targeted drug achieves longer survival in orthotopic pancreatic cancer model.

Research Products

• [Journal Article] The Akt/mTOR pathway assures the synthesis of HIF-1alpha protein in a glucose- and reoxygenation-dependent manner in irradiated tumors. (2009)
  • Author(s): Harada H, Itasaka S, Kizaka-Kondoh S, Shibuya K, Morinibu A, Shinomiya K, Hiraoka M
  • Journal Title: J Biol Chem 284(8) Pages: 5332-5342
  • Peer Reviewed
• [Journal Article] Treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the effect of radiation therapy. (2009)
  • Author(s): Harada H, Itasaka S, Zhu Y, Zeng L, Xie X, Morinibu A, Shinomiya K, Hiraoka M
  • Journal Title: Br J Cancer. 100(5) Pages: 747-757
  • Peer Reviewed
• [Journal Article] Selective killing of hypoxia-inducible factor-1-active cells improves survival in a mouse model of invasive and metastatic pancreatic cancer. (2009)
  • Author(s): Kizaka-Kondoh S, Itasaka S, Zeng L, Tanaka S, Zhao T, Takahashi Y, Shibuya K, Hirota K, Semenza GL, Hiraoka M
  • Journal Title: Clin Cancer Res. 15(10) Pages: 3433-3441
  • Peer Reviewed
• [Journal Article] Usefulness of HIF-1 imaging for determining optimal timing of combining Bevacizumab and radiotherapy. (2009)
  • Author(s): Ou G, Itasaka S, Zeng L, Shibuya K, Yi J, Harada H, Hiraoka M
  • Journal Title: Int J Radiat Oncol Biol Phys. 75(2) Pages: 463-467
  • Peer Reviewed
• [Journal Article] Diameter of tumor blood vessels is a good parameter to estimate HIF-1-active regions in solid tumors. (2008)
  • Author(s): Harada H, Xie X, Itasaka S, Zeng L, Zhu Y, Morinibu A, Shinomiya K, Hiraoka M.
  • Journal Title: Biochem Biophys Res Commun. 373(4) Pages: 533-538
  • Peer Reviewed
• [Journal Article] TS-1 enhances the effect of radiotherapy by suppressing radiation-induced hypoxia-inducible factor-1 activation and inducing endothelial cell apoptosis. (2008)
  • Author(s): Zeng, L., Ou G, et al.. Zeng L, Ou G, Itasaka S, Harada H, Xie X, Shibuya K, Kizaka-Kondoh S, Morinibu A, Shinomiya K, Hiraoka M
  • Journal Title: Cancer Sci 99(11) Pages: 2327-2335
  • Peer Reviewed
• [Book] The Impact of Tumor Biology on Cancer Treatment and Multidisciplinary Strategies Stratedies;Treatment of the Primary Tumor in Metastatic Cancer: Influence on Outcome.(Chapter 21) (2009)
  • Author(s): Itasaka S, Hiraoka M
  • Total Pages: 347-354