Antitumor Action of the MET Tyrosine Kinase Inhibitor in Gastric Cancer Positive for MET Amplification

• Project/Area Number: 24501360
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: National Cancer Center Japan (2013-2014); Kinki University (2012)
• Principal Investigator: OKAMOTO Wataru 独立行政法人国立がん研究センター, 早期・探索臨床研究センター, 医員 (30441075)
• Co-Investigator(Kenkyū-buntansha): NAKAGAWA Kazuhiko 近畿大学, 医学部, 教授 (40298964) ; NISHIO Kazuto 近畿大学, 医学部, 教授 (10208134) ; OKAMOTO Isamu 九州大学, 大学病院, 学術研究員 (10411597) ; ARAO Tokuzo 近畿大学, 医学部, 講師 (20441074)
• Research Collaborator: KAWAKAMI Hisato
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: MET遺伝子増幅 / 胃癌 / 分子標的薬 / Gastric Cancer / MET / Resistance / 分子標的治療

Outline of Final Research Achievements

We previously showed that induction of apoptosis underlies the antiproliferative effect of MET tyrosine kinase inhibitors (MET-TKIs) in gastric cancer cells with MET amplification. In the present study, we showed the molecular mechanism underlying its MET-TKIs-induced apoptosis. We also determined the prevalence, clinical features and prognosis of gastric cancer with MET amplification. We further established the MET-TKIs-resistant gastric cancer cell lines, which is important to reveal the MET-TKIs-resistant mechanisms.

Research Products

• [Journal Article] Targeting MET Amplification as a New Oncogenic Driver. (2014)
  • Author(s): Kawakami H, Okamoto I, Okamoto W, Tanizaki J, Nakagawa K, Nishio K.
  • Journal Title: Cancers(Basel) Volume: 6(3) Issue: 3 Pages: 1540-52
  • DOI: 10.3390/cancers6031540
  • Peer Reviewed / Open Access
• [Journal Article] MET amplification as a potential therapeutic target in gastric cancer. (2013)
  • Author(s): Kawakami H, Okamoto I, Arao T, Okamoto W, Matsumoto K, Taniguchi H, Kuwata K, Yamaguchi H, Nishio K, Nakagawa K, Yamada Y.
  • Journal Title: Oncotarget Volume: 4(1) Pages: 9-17
  • Peer Reviewed
• [Journal Article] Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification. (2012)
  • Author(s): Okamoto W, Okamoto I, Arao T, Kuwata K, Hatashita E, Yamaguchi H, Sakai K, Yanagihara K, Nishio K, Nakagawa K.
  • Journal Title: Mol Cancer Ther Volume: 11(7) Pages: 1557-1564
  • Peer Reviewed
• [Presentation] Antitumor action of the MET tyrosine kinase inhibitor crizotinib in gastric cancer positive for MET amplification (2013)
  • Author(s): Wataru Okamoto, Isamu Okamoto, Hisato Kawakami, Kazuyoshi Yanagihara, Kazuto Nishio, Kazuhiko Nakagawa
  • Organizer: International Symposium of Korean Society of Gastrointestinal Cancer
  • Place of Presentation: Seoul, Korea
• [Presentation] MET遺伝子増幅陽性胃癌に対するMETチロシンキナーゼ阻害剤クリゾチニブの抗腫瘍効果 (2012)
  • Author(s): 岡本渉、岡本勇、荒尾徳三、仁科慎一、上田眞也、川上尚人、柳原五吉、倉田宝保、西尾和人、中川和彦
  • Organizer: 第10回日本臨床腫瘍学会学術集会
  • Place of Presentation: 大阪府大阪市 大阪国際会議場