Establishment of the second line chemotherapy for esophageal cancer using poly (ADP-ribose) polymerase inhibitors

• Project/Area Number: 16K18964
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Minegaki Tetsuya 京都薬科大学, 薬学部, 助教 (10549306)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 食道癌 / PARP阻害剤 / 相乗効果 / DNA損傷修復 / セカンドライン

Outline of Final Research Achievements

The purpose of this study is to clarify the efficacy of poly (ADP-ribose) polymerase (PARP) inhibitor in esophageal cancer chemotherapy. This study indicated that PARP inhibitors such as olaparib synergistically potentiates the sensitivity to anticancer drugs, especially DNA-damaging agents, in human esophageal cancer cell lines. In addition, the potentiation of sensitivity to anticancer drugs by olaparib was involved in cell signals related to p53-binding protein (53BP1).

Academic Significance and Societal Importance of the Research Achievements

本研究成果から、食道癌化学療法においてオラパリブのようなPARP阻害剤が有用であること、また特に癌細胞のDNAを損傷させる抗癌剤と併用することで相乗的な抗腫瘍効果を得ることができる可能性が示唆された。本研究成果が、食道癌化学療法において薬剤選択の幅を広げるための一助となることが期待される。また、この成果により食道癌のみならず他の癌種への検討に繋がる学術的な波及効果も期待できると考えられる。

Research Products

• [Journal Article] Synergistic Effects of Olaparib and DNA-damaging Agents in Oesophageal Squamous Cell Carcinoma Cell Lines. (2019)
  • Author(s): Keisuke Miyamoto, Tetsuya Minegaki, Mami Tanahashi, Ayaka Yamamoto, Yumi Moriyama, Akari Wada, Ayaka Matsumoto, Keisuke Ota, Mai Tanaka, Utako Masuda, Masayuki Tsujimoto, Kohshi Nishiguchi
  • Journal Title: Anticancer Research Volume: 39 Issue: 4 Pages: 1813-1820
  • DOI: 10.21873/anticanres.13288
  • Peer Reviewed
• [Presentation] 53BP1の発現抑制は食道癌細胞株におけるPARP阻害剤と抗癌剤との相乗的な細胞毒性を減弱させる (2019)
  • Author(s): 平野沙耶香、峯垣哲也、宮本恵輔、林逸佳、青山淑美、西野翔太、辻本雅之、西口工司
  • Organizer: 日本薬学会第139年会
• [Presentation] ヒト食道癌細胞株の抗癌剤感受性に及ぼすポリ(ADPリボース) ポリメラーゼ阻害剤オラパリブの影響 (2017)
  • Author(s): 宮本恵輔、峯垣哲也、森山由美、和田明莉、松本彩夏、太田圭祐、田中麻衣、増田詩子、棚橋真実、山本彩佳、荒木悠、稲垣恵未、林絵里、辻本雅之、西口工司
  • Organizer: 第67回 日本薬学会近畿支部総会・大会
• [Presentation] The Poly (ADP-ribose) Polymerase Inhibitor, Olaparib, Potentiates the Cytotoxic Effects of Anti-Cancer Drugs in Human Esophageal Squamous Cell Carcinoma Cell Lines (2016)
  • Author(s): Tetsuya Minegaki, Keisuke Miyamoto, Mami Tanahashi, Ayaka Yamamoto, Yu Araki, Megumi Inagaki, Eri Hayashi, Masayuki Tsujimoto, Kohshi Nishiguchi
  • Organizer: 2016 AAPS Annual Meeting and Exposition
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 2016-11-13
  • Int'l Joint Research