Development of novel drugs for pancreatic cancer targeting Glypican-1

• Project/Area Number: 20K16960
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kochi University
• Principal Investigator: Uemura Sunao 高知大学, 医学部, 客員助教 (80566191)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 膵癌 / GPC-1 / Glypican-1

Outline of Research at the Start

膵癌は早期診断が難しく、術後早期の転移や再発を来すことから化学療法の重要性が高く、新規治療薬の開発が強く望まれている。そこで本研究では、Glypican-1（GPC-1）が膵癌において高発現していることに着目し、GPC-1を標的とした抗体薬物複合体（Antibody-Drug Conjugate; ADC）であるGPC-1-ADCが膵癌の新規治療薬になり得るのではと考えた。本研究においてGPC-1を標的としたADCが膵癌の新規治療薬になり得ることを示すことができれば、最も悪性で難治性の膵癌の治療に道を拓くことになる。

Outline of Final Research Achievements

Pancreatic ductal adenocarcinoma (PDAC) is a stroma-rich cancer. GPC1-ADC(MMAE) exhibited potent and unique antitumor activity in GPC1-positive PDAC PDX models, which suggests that GPC1 is a novel therapeutic target in PDAC and other stromal GPC1-positive solid tumors. These findings show that targeting GPC1 on CAF using GPC1-ADC(MMAE) is a useful approach in case of stroma-rich tumors such as PDAC.

Academic Significance and Societal Importance of the Research Achievements

GPC1 が、膵癌患者における間質障壁による不十分な薬物送達を克服できる抗体の有望な標的である可能性を示した。これらの結果は、今後膵癌治療の選択肢を広げる重要な知見であると考えられる。

Research Products

• [Journal Article] Gastrointestinal: Giant gallbladder (2022)
  • Author(s): Uemura S、Namikawa T、Uchida K、Hanazaki K
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: 37 Issue: 12 Pages: 2206-2206
  • DOI: 10.1111/jgh.15858
  • Peer Reviewed / Open Access
• [Journal Article] Gastrointestinal: Abdominal eggshell sign in a young woman with a pancreatic solid pseudopapillary neoplasm (2022)
  • Author(s): Uemura S、Maeda H、Fujisawa K、Uchida K、Hanazaki K
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: 38 Issue: 5 Pages: 682-682
  • DOI: 10.1111/jgh.16016
  • Peer Reviewed
• [Journal Article] Adverse effects of prolonged postoperative hospital stay on long-term survival of pancreatic adenocarcinoma (2021)
  • Author(s): Uemura Sunao、Sugiura Teiichi、Okamura Yukiyasu、Ito Takaaki、Yamamoto Yusuke、Ashida Ryo、Hanazaki Kazuhiro、Uesaka Katsuhiko
  • Journal Title: Annals of Cancer Research and Therapy Volume: 29 Issue: 1 Pages: 11-16
  • DOI: 10.4993/acrt.29.11
  • NAID: 130007975530
  • ISSN: 1344-6835, 1880-5469
  • Year and Date: 2021-01-08
  • Peer Reviewed / Open Access
• [Journal Article] Anti-Glypican-1 Antibody-drug Conjugate as Potential Therapy Against Tumor Cells and Tumor Vasculature for Glypican-1-Positive Cholangiocarcinoma (2021)
  • Author(s): Yokota Keiichiro、Serada Satoshi、Tsujii Shigehiro、Toya Keisuke、Takahashi Tsuyoshi、Matsunaga Takashi、Fujimoto Minoru、Uemura Sunao、Namikawa Tsutomu、Murakami Ichiro、Kobayashi Shogo、Eguchi Hidetoshi、Doki Yuichiro、Hanazaki Kazuhiro、Naka Tetsuji
  • Journal Title: Molecular Cancer Therapeutics Volume: 20 Issue: 9 Pages: 1713-1722
  • DOI: 10.1158/1535-7163.mct-21-0015
  • Peer Reviewed
• [Journal Article] A glypican-1-targeted antibody-drug conjugate exhibits potent tumor growth inhibition in glypican-1-positive pancreatic cancer and esophageal squamous cell carcinoma (2021)
  • Author(s): Munekage Eri、Serada Satoshi、Tsujii Shigehiro、Yokota Keiichiro、Kiuchi Keita、Tominaga Kenji、Fujimoto Minoru、Kanda Mizuki、Uemura Sunao、Namikawa Tsutomu、Nomura Taisei、Murakami Ichiro、Hanazaki Kazuhiro、Naka Tetsuji
  • Journal Title: Neoplasia Volume: 23 Issue: 9 Pages: 939-950
  • DOI: 10.1016/j.neo.2021.07.006
  • Peer Reviewed / Open Access
• [Presentation] Glypican-1を標的とするADC(Antibody-drug conjugate)を用いた胆管癌の新規治療開発 (2021)
  • Author(s): 横田 啓一郎, 世良田 聡, 辻井 茂宏, 遠矢 圭介, 高橋 剛, 藤本 穰, 上村 直, 並川 努, 村上 一郎, 小林 省吾, 江口 英利, 土岐 祐一郎, 花崎 和弘, 仲 哲治
  • Organizer: 第57回日本胆道学会
• [Presentation] Successful conversion surgery for advanced pancreatic acinar carcinoma with a solitary dissemination after FOLFILINOX treatment: a case report (2020)
  • Author(s): Sunao Uemura, Hiromichi Maeda, Nobuhisa Tanioka, Masaya Munekage, Tsutomu Namikawa, Kazuhiro Hanazaki
  • Organizer: 第32回日本肝胆膵外科学会・学術集会