Prediction of the phosphorylation signal response of receptor-type tyrosine kinase (RTK) inhibitors using miRNA as a biomarker.

• Project/Area Number: 15K08083
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Meiji Pharmaceutical University
• Principal Investigator: Suzuki Toshihiro 明治薬科大学, 薬学部, 准教授 (80322527)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: miRNA / RTK阻害薬 / キナーゼシグナル / バイオマーカー / リン酸化シグナル / 分子標的薬 / キナーゼ阻害剤

Outline of Final Research Achievements

This study was performed that predicting the effect of receptor type tyrosine kinase (RTK) inhibitors with miRNA as a biomarker.　We found that miR-205 was overexpressed in Gefinitib-resistant lung cancer cell lines with MET amplification. The reporter assay system was developed for kinase signal prediction in gefitinib resistant lung cancer cell lines. This screening system revealed that miR-205 expression was down regulated by pI3K Akt inhibitors. In conclusion, clarified the possibility of phosphorylation signal as a regulator of the miRNA expression.

Research Products

• [Journal Article] Stereoselective total synthesis of (-)-renieramycin T (2016)
  • Author(s): Yokoya M., Toyoshima R., Suzuki T., Le V. H., Williams R. M., Saito N.
  • Journal Title: J. Org. Chem. Volume: 81 Issue: 10 Pages: 0001-0009
  • DOI: 10.1021/acs.joc.6b00327
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Chemistry of Ecteinascidins. Part 5: An Additional Proof of Cytotoxicity Evaluation of Ecteinascidin 770 Derivatives (2016)
  • Author(s): Toyoshima R, Mori N, Suzuki T, Lowtangkitcharoen W, Suwanborirux K, Saito N
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 64 Issue: 7 Pages: 966-969
  • DOI: 10.1248/cpb.c16-00192
  • NAID: 130005160038
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Utilization of arsenic trioxide as a treatment of cisplatin-resistant non-small cell lung cancer PC-9/CDDP and PC-14/CDDP cells. (2015)
  • Author(s): Suzuki T, Ishibashi K, Yumoto A, Nishio K, Ogasawara Y.
  • Journal Title: Oncol Lett. Volume: 10(2) Issue: 2 Pages: 805-809
  • DOI: 10.3892/ol.2015.3352
  • Peer Reviewed / Open Access
• [Presentation] Tyrosine kinase inhibitor resistance were decreased in spheroid culture platform： (2017)
  • Author(s): Suzuki T, Ito R, Yamaoka T, Ohmori T, Nishio K, Ogasawara Y
  • Organizer: The 108th Annual Meeting of the American Association for Cancer Research
  • Int'l Joint Research
• [Presentation] ３次元培養法を用いた抗がん剤に対する薬剤耐性の評価： (2017)
  • Author(s): 伊東里紗、鈴木俊宏、山岡利光、大森 亨、西尾 和人、小笠原 裕樹
  • Organizer: 2017年度生命科学系合同年次大会、第90回日本生化学会大会
• [Presentation] The effect of kinase signaling for miR-205 regulation in gefitinib resistant lung cancer cell lines (2016)
  • Author(s): Suzuki T., Ito R.,,Yamaoka T., Ohmori T., Nishio K.,Ogasawara Y
  • Organizer: Annual meeting of American association for cancer research
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] The effect of kinase signaling for miR-205 regulation in gefitinib resistant lung cancer cell lines (2016)
  • Author(s): Toshihiro Suzuki, Ikuko Nagasawa, Toshimitsu Yamaoka, Tohru Ohmori, Kazuto Nishio, Kiyotaka Koyama, Yuki Ogasawara
  • Organizer: Annual Meeting of American Association for Cancer Research
  • Place of Presentation: New Orleans LA, USA
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] The effect of ErbB3 phosphorylation for miR-205 regulation in gefitinib-resistant lung cancer cell lines (2015)
  • Author(s): Toshihiro Suzuki, Ikuko Nagasawa, Toshimitsu Yamaoka, Tohru Ohmori, Kazuto Nishio, Kiyotaka Koyama, Yuki Ogasawara
  • Organizer: 日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08