The exploration of novel therapeutic target in gastric cancer by comprehensive tyrosine-kinase analysis

• Project/Area Number: 23591930
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: YAMASAKI Makoto 大阪大学, 医学(系)研究科(研究院), 助教 (50444518)
• Co-Investigator(Kenkyū-buntansha): TAKIGUCHI Shuuji 大阪大学, 医学部付属病院消化器外科, 講師 (00301268) ; MIYATA Hiroshi 大阪大学, 医学部付属病院消化器外科, 講師 (80362713) ; KUROKAWA Yukinori 大阪大学, 医学部付属病院消化器外科, 助教 (10470197)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 胃癌 / チロシンキナーゼ / 腹膜播種 / 網羅的発現解析 / 化学療法感受性

Research Abstract

We analyzed the comprehensive gene expression in gastric cancer to explore the novel tyrosine-kinase related to the development of cancer, especially peritoneal dissemination. Then the novel and well-known tyrosine-kinases; KSR1 and MEK, Her2 and FGFR1 were identified. KSR1 is a tyrosine-kinase that functions as positive regulator of Ras pathway, and associated with the cell motility, invasion and peritoneal dissemination. FOXM1, DOK2 and REGIV are identified as the downstream molecules of the tyrosine-kinases, MEK, Her2 and FGFR1, respectively in consequence of the analysis of the correlativity between the pathways of these tyrosine-kinases and gene expression analysis. It was shown that these molecules related with the prognosis, peritoneal dissemination and the sensitivity of anticancer drug.
This result may enable us to elucidate the signaling related to the biological character of gastric cancer and develop the novel molecular-targeted agent.

Research Products

• [Journal Article] Overexpression of forkhead box M1 transcription factor (FOXM1) is a potential prognostic marker and enhances chemoresistance for docetaxel in gastric cancer (2013)
  • Author(s): Okada K, Fujiwara Y, Takahashi T, Nakamura Y, Takiguchi S, Nakajima K, Miyata H, Yamasaki M, Kurokawa Y, Mori M, Doki Y.
  • Journal Title: Ann Surg Oncol Volume: 20(3) Pages: 1035-43
• [Journal Article] Overexpression of forkhead box M1 transcription factor (FOXM1) is a potential prognostic marker and enhances chemoresistance for docetaxel in gastric cancer (2013)
  • Author(s): Okada Kaoru, Fujiwara Yosiyuki, Takahashi Tsuyoshi, Nakamura Yusuke, Takiguti Syuji, Nakajima Kiyokazu, Miyata Hiroshi, Yamasaki Makoto, Kurokawa Yukinori, Mori Masaki,and Doki Yuichiro
  • Journal Title: Annals of Surgical Oncology Volume: 20 Issue: 3 Pages: 1035-1043
  • DOI: 10.1245/s10434-012-2680-0
  • Peer Reviewed
• [Journal Article] DOK2 as a marker of poor prognosis of patients with gastric adenocarcinoma after curative resection (2012)
  • Author(s): Miyagaki H, Yamasaki M, Takahashi T, Kurokawa Y, Miyata H, Nakajima K, Takiguchi S, Fujiwara Y, Mori M, Doki Y.
  • Journal Title: Ann Surg Oncol Volume: 19(5) Pages: 1560-7
• [Journal Article] REGIV as a potential biomarker for peritoneal dissemination in gastric adenocarcinoma (2012)
  • Author(s): Moon JH, Fujiwara Y, Nakamura Y, Okada K, Hanada H, Sakakura C, Takiguchi S, Nakajima K, Miyata H, Yamasaki M, Kurokawa Y, Mori M, Doki Y.
  • Journal Title: J Surg Oncol Volume: 105(2) Pages: 189-94
• [Journal Article] DOK2 as a marker of poor prognosis of patients with gastric adenocarcinoma after curative resection (2011)
  • Author(s): Hiromichi Miyagaki, Makoto Yamasaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Hiroshi Miyata, Kiyokazu Nakajima, Shuji Takiguchi, Yoshiyuki Fujiwara, Masaki Mori, Yuichiro Doki
  • Journal Title: Annals of Surgical Oncology Volume: Epub ahead of print
  • Peer Reviewed
• [Presentation] 胃癌におけるFoxM1の発現と薬剤耐性についての検討 (2012)
  • Author(s): 岡田かおる
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2012-04-12