Development of precision medicine for patients with pancreatic cancer who harbor homologous recombinant repair genes

• Project/Area Number: 17K08413
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kyoto University
• Principal Investigator: KANAI MASASHI 京都大学, 医学研究科, 准教授 (70432416)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 膵がん / ゲノム医療 / BRCA / 相同修復組み換え遺伝子 / 個別化医療 / 膵癌 / オキサリプラチン / ゲノム / がん遺伝子パネル検査 / DNA修復異常 / 相同組み換え修復異常 / 白金製剤 / 次世代シーケンス

Outline of Final Research Achievements

We aimed to evaluate the association between homologous recombinant repair (HRR) gene mutations and the efficacy of oxaliplatin-based chemotherapy in patients with pancreatic cancer. We designed a new gene panel comprising 8 HRR related genes （ATM, ATR, BRCA1, BRCA2, PALB2, RAD51B, RAD51C, RAD51D）and 27 cancer related genes. Gene panel test was run by the CLIA certified laboratory.　We launched a prospective observational study to evaluate the association between HRR gene mutations and the efficacy of oxaliplatin-based chemotherapy in patients with pancreatic cancer from May 2018 after the approval of institutional review board. We completed the enrollment of 40 patients in March 2020. Among 40 patients, only one patient failed the sequencing due to the lack of DNA. Loss of function mutations in HRR related genes were detected in 9 patients out of 39 (23%). After one-year observational period, we plan to perform the final analysis.

Academic Significance and Societal Importance of the Research Achievements

2019年よりがん遺伝子パネル検査が保険承認され、国内におけるゲノム医療も本格化している。膵癌においてもゲノム情報に基づく個別化医療開発が活発化しており、生殖細胞レベルでBRCA変異を有する膵癌に対するPARP阻害薬の維持療法の有用性が第Ⅲ相臨床試験で証明され、海外では実地臨床に導入されている。本研究は体細胞レベルでのBRCAを含む相同修復組み換え遺伝子異常と白金製剤であるオキサリプラチンの効果を前向きに調べた初めての臨床試験であり、その成果は膵癌の個別化医療推進に寄与するものと考える。

Research Products

• [Journal Article] Association between homologous recombination repair gene mutations and response to oxaliplatin in pancreatic cancer (2018)
  • Author(s): Kondo Tomohiro、Kanai Masashi、Kou Tadayuki、Sakuma Tomohiro、Mochizuki Hiroaki、Kamada Mayumi、Nakatsui Masahiko、Uza Norimitsu、Kodama Yuzo、Masui Toshihiko、Takaori Kyoichi、Matsumoto Shigemi、Miyake Hidehiko、Okuno Yasushi、Muto Manabu
  • Journal Title: Oncotarget Volume: 9 Issue: 28 Pages: 19817-19825
  • DOI: 10.18632/oncotarget.24865
  • Peer Reviewed / Open Access
• [Presentation] Association between homologous recombination repair gene mutations and response to oxaliplatin in pancreatic cancer (2019)
  • Author(s): Masashi Kanai
  • Organizer: 50th Annual Scientific Meeting of American Pancreatic Association
  • Int'l Joint Research / Invited
• [Presentation] がん関連遺伝子パネル (OncoPrimeTM) を用いたprecision medicine (2017)
  • Author(s): 金井雅史、髙忠之、松本繁巳、武藤学
  • Organizer: 第3回日本産科婦人科遺伝診療学会
  • Invited
• [Book] 肝と膵 (2019)
  • Author(s): 金井 雅史
  • Total Pages: 4
  • Publisher: 医学図書出版