The efficacy of PARP inhibitor against gastrointestinal cancer

• Project/Area Number: 25460930
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: Kubota Eiji 名古屋市立大学, 医学(系)研究科(研究院), 講師 (30405188)
• Co-Investigator(Kenkyū-buntansha): KATAOKA HIROMI 名古屋市立大学, 医学(系)研究科(研究院), 准教授 (40381785) ; MIURA YUTAKA 名古屋市立大学, 医学(系)研究科(研究院), 准教授 (90285198)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 消化器癌 / ATM / PARP阻害剤 / 胃癌 / 大腸癌

Outline of Final Research Achievements

In this study, we revealed the efficacy of PARP inhibitor is significantly associated with the expression level of Ataxia telangiectasia mutated (ATM) protein. Additionally, we showed that ATM inhibitor sensitized the effect of PARP inhibitor in gastric cancer cell lines with p53 disruption. Our study demonstrated the utility of ATM as a biomarker of PARP inhibitor for gastric cancer patients. Moreover, our date revealed the possibility that PARP inhibitor in combination with ATM inhibitor is effective for p53-mutant gastric cancer.

Research Products

• [Journal Article] Low ATM protein expression and depletion of p53 correlates with olaparib sensitivity in gastric cancer cell lines (2014)
  • Author(s): Kubota E, Williamson CT, Elegbede A, Ruiqiong Y, Peterson L, Bebb DG, Lees-Miller SP
  • Journal Title: Cell cycle Volume: 13 Issue: 13 Pages: 2129-2137
  • DOI: 10.4161/cc.29212
  • Peer Reviewed
• [Presentation] ATMをバイオマーカーとした胃癌に対するPARP阻害剤の有効性の検討 (2015)
  • Author(s): 久保田英嗣
  • Organizer: 第１０２回 日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京、新宿）
  • Year and Date: 2015-04-21
• [Presentation] 胃癌に対するPARP阻害剤の効果 (2014)
  • Author(s): 久保田英嗣、片岡洋望、城卓志
  • Organizer: 第25回消化器癌発生学会総会/第8回国際消化器癌発生会議
  • Place of Presentation: ホテル日航福岡（福岡県・福岡市）
  • Year and Date: 2014-11-14 – 2014-11-15
• [Presentation] 胃癌におけるATM, p53発現と新規分子標的薬PARP阻害剤感受性 (2014)
  • Author(s): 久保田英嗣、片岡洋望、城卓志
  • Organizer: 第73回日本癌学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ATM and p53 expression level correlate with sensitivity to olaparib in gastric cancer.
  • Author(s): Eiji Kubota
  • Organizer: Digestive Disease Week 2014
  • Place of Presentation: mcCormic Place, Chicago, Illinois