Developing effective combination therapy with ATP competitive tyrosine kinase inhibitors

• Project/Area Number: 15H05666
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Keio University
• Principal Investigator: Yasuda Hiroyuki 慶應義塾大学, 医学部(信濃町), 講師 (70365261)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000); Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: 肺癌 / 分子標的治療薬 / ＡＴＰ濃度 / ATP濃度 / 癌 / ATP競合型チロシンキナーゼ阻害剤 / ATP

Outline of Final Research Achievements

Recently, multiple molecular targeted drugs have been developed.Of these molecular targeted drugs, ATP competitive tyrosine kinase in hibitors improved the prognosis of lung cancer patients. Depending on the findings that ATP concentration of the cancer cells affect the efficacy of the ATP competitive tyrosine kinase inhibitors, we tried to develop a combination therapy with drugs which lower the ATP concentration of cancer cells and ATP-competitive tyrosine kinase inhibitors. By exmaining the effect of multiple druds on the ATP concentration of cancer cells, we have identified several drugs which lower the ATP concentration of cancer cells.

Research Products

• [Journal Article] Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors. (2017)
  • Author(s): Nukaga S, Yasuda H, Tsuchihara K, Hamamoto J, Masuzawa K, Kawada I, Naoki K, Matsumoto S, Mimaki S, Ikemura S, Goto K, Betsuyaku T, Soejima K.
  • Journal Title: Ｃａｎｃｅｒ Ｒｅｓｅａｒｃｈ Volume: 77（８） Issue: 8 Pages: 2078-2089
  • DOI: 10.1158/0008-5472.can-16-2359
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Overcoming EGFR Bypass Signal-Induced Acquired Resistance to ALK Tyrosine Kinase Inhibitors in ALK-Translocated Lung Cancer. (2017)
  • Author(s): Miyawaki M, Yasuda H, Tani T, Hamamoto J, Arai D, Ishioka K, Ohgino K, Nukaga S, Hirano T, Kawada I, Naoki K, Hayashi Y, Betsuyaku T, Soejima K.
  • Journal Title: Ｍｏｌｅｃｕｌａｒ Ｃａｎｃｅｒ Ｒｅｓｅａｒｃｈ Volume: 15(1） Issue: 1 Pages: 106-114
  • DOI: 10.1158/1541-7786.mcr-16-0211
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Activation of EGFR baypass Signaling by TGFα Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells (2016)
  • Author(s): Tani T, Yasuda H, Hamamoto J, Kuroda A, Arai D, Ishioka K, Ohgino K, Miyawaki et al.
  • Journal Title: Molecular Cancer Therapeutics Volume: 15(1) Pages: 162-71
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer (2016)
  • Author(s): Hirano T, Yasuda H, Tani T, Hamamoto J, Oashi A, Ishioka K, Arai D, Nukaga S, Miyawaki M, Kawada I, Naoki K, Costa DB, Kobayashi SS, BetsuyakuT, Soejima K
  • Journal Title: Oncotarget Volume: 17 Issue: 36 Pages: 38789-803
  • DOI: 10.18632/oncotarget.5887
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant