Mechanism of PI3K activation and individualized anti-kinase therapy in gastric cancer

• Project/Area Number: 21790522
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Applied pharmacology
• Research Institution: Kobe University
• Principal Investigator: MUKOHARA Toru Kobe University, 医学部附属病院, 特命准教授 (80435718)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: シグナル伝達 / 個別化治療 / 胃がん / PI3K

Research Abstract

Foretinib, the novel muti-kinase inhibitor, appears effective against gastric cancer cells harboring not only MET but also FGFR2 amplification. There appears inter-RTK signaling networks with MET or FGFR2 at their core in at least part of gastric cancer cells, and the networks may contribute to efficient PI3K signaling. Foretinib exerts its inhibitory effects by blocking the networks.

Research Products

• [Journal Article] Association between gain-of function mutations in PIK3CA and resistance to HER2-targeted agents in HER2-amplified breast cancer cell lines. (2009)
  • Author(s): Kataoka Y, Mukohara T, et al
  • Journal Title: Annals of Oncology 21 Pages: 255-262
  • Peer Reviewed
• [Presentation] Foretinib (GSK1363089) inhibits growth of gastric cancer cell lines through blockade of inter-receptor tyrosine kinase networks (2010)
  • Author(s): Mukohara T, Kataoka Y, Tomioka H, Kiyota N, et al.
  • Organizer: 22nd EORTC-NCI-AACR symposium on "Molecular Targets and Cancer Therapeutics"
  • Place of Presentation: ベルリン(ドイツ)
  • Year and Date: 2010-11-17
• [Presentation] Foretinib (GSK1363089) inhibits growth of gastric cancer cell lines through blockade of inter-receptor tyrosine kinases networks. (2010)
  • Author(s): Mukohara T, Kataoka Y, Tomioka H, Kiyota N, Fujiwara Y, Yashiro M, Hirai M, Minami H.
  • Organizer: 22^<nd> EORTC-NCI-AACR symposium on "Molecular Targets and Cancer Therapeutics"
• [Presentation] PI3K inhibitors overcome resistance to HER2-targeted agents caused by PIK3CA mutations in HER2-amplified breast cancer cell lines. (2009)
  • Author(s): Kataoka Y, Mukohara T, et al
  • Organizer: 21st EORTC-NCI-AACR symposium on "Molec-ular Targets and Cancer Therapeutics"
  • Place of Presentation: ボストン(米国)
  • Year and Date: 2009-11-15