Identification of target for next generation tyrosine kinase inhibitor and clinical markers for sensitive patients

• Project/Area Number: 23390147
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: The University of Tokyo
• Principal Investigator: TAKAI Daiya 東京大学, 医学部附属病院, 講師 (90361493)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2013: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2011: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 肺がん / チロシンキナーゼ / ＦＥＲ / ＲＥＴ / 腫瘍検査学 / 個別化医療

Research Abstract

In Japan, more than sixty thousand patients are killed by lung cancer a year. Recent progress in development of molecular targeting medicine, we analyzed expression level of tyrosine kinases which have homology with ALK tyrosine kinase. We identified FER as possible target gene. In NCI-H661 cells, FER was overexpressed and knockdown of FER by siRNA induced apoptosis of the cells. In clinical specimen, approximately ten percent of lung cancer overexpressed FER and their postoperative outcome was poorer. We published these data and started collaboration with pharmaceutical company to develop FER inhibitors to cure lung cancer.

Research Products

• [Journal Article] Combined Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Epidermal Growth Factor Receptor Mutation in a Female Patient Who Never Smoked (2014)
  • Author(s): Yoshida Y, Ota S, Murakawa T, Takai D
  • Journal Title: Annals of Thoracic and Cardiovascular Surgery Volume: 20 Issue: Supplement Pages: 582-584
  • DOI: 10.5761/atcs.cr.12.02217
  • NAID: 130003377861
  • ISSN: 1341-1098, 2186-1005
  • Peer Reviewed
• [Journal Article] Growth-associated hyperphosphatemia in young recipients accelerates aortic allograft calcification in a rat model (2013)
  • Author(s): Yamauchi H, Motomura N, Chung UI, Sata M, Takai D, Saito A, Ono M, Takamoto S
  • Journal Title: J Thorac Cardiovasc Surg Volume: 145(2) Pages: 522-530
• [Journal Article] Uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1) polymorphisms are associated with toxicity and efficacy in irinotecan monotherapy for refractory pancreatic cancer (2013)
  • Author(s): Takahara N, Nakai Y, Isayama H, Sasaki T, Satoh Y, Takai D, Hamada T, Uchino R, Mizuno S, Miyabayashi K, Mohri D, Kawakubo K, Kogure H, Yamamoto N, Sasahira N, Hirano K, Ijichi H, Tada M, Yatomi Y, Koike K
  • Journal Title: Cancer Chemother Pharmacol Volume: 71(1) Pages: 85-92
• [Journal Article] High-grade lung adenocarcinoma with fetal-lung-like morphology - Clinicopathological, immunohistochemical, and molecular analyses of 17 cases (2013)
  • Author(s): Morita S, Yoshida A, Goto A, Ota S, Tsuta K, Yokozawa K, Asamura H, Nakajima J, Takai D, Mori M, Oka T, Tamaru J, Itoyama S, Furuta K, Fukayama M, Tsuda H
  • Journal Title: American J of Surg. Pathology Volume: 37(6) Pages: 924-932
• [Journal Article] FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer (2013)
  • Author(s): Kawakami M, Morita S, Sunohara M, Amano Y, Ishikawa R, Watanabe K, Hamano E, Ohishi N, Nakajima J, Yatomi Y, Nagase T, Fukayama M, Takai D
  • Journal Title: Int J Clin Exp Pathol Volume: 6(4) Pages: 598-612
• [Journal Article] A pilot study of salvage irinotecan monotherapy for advanced biliary tract cancer (2013)
  • Author(s): Sasaki T, Isayama H, Nakai Y, Takahara N, Satoh Y, Takai D, Kogure H, Yamamoto N, Hirano K, Tada M, Yatomi Y, Koike K
  • Journal Title: Anticancer Res Volume: 33(6) Pages: 2619-2622
• [Journal Article] Combined Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Epidermal Growth Factor Receptor Mutation in a Female Patient Who Never Smoked (2013)
  • Author(s): Yoshida Y, Ota S, Murakawa T, Takai D, Nakajima J
  • Journal Title: Ann Thorac Cardiovasc Surg
  • NAID: 130003377861
• [Journal Article] Detection of novel paraja ring finger 2-fer tyrosine kinase mRNA chimeras is associated with poor postoperative prognosis in non-small cell lung cancer (2013)
  • Author(s): Kawakami M, Ishikawa R, Amano Y, Sunohara M, Watanabe K, Ohishi N, Yatomi Y, Nakajima J, Fukayama M, Nagase T, Takai D
  • Journal Title: Cancer Sci Volume: 104(11) Pages: 1447-1454
• [Journal Article] Successful Treatment of Mediastinal Unicentric Castleman's Disease Using Video-Assisted Thoracoscopic Surgery with Preoperative Embolization (2013)
  • Author(s): Amano Y, Takai D, Ohishi N, Shinozaki-Ushiku A, Fukayama M, Akahane M, Nakajima J, Nagase T
  • Journal Title: Case Rep Med Volume: 2013 Pages: 354507-354507
• [Journal Article] Disruption of the expression and function of microRNAs in lung cancer as a result of epigenetic changes (2013)
  • Author(s): Watanabe K & Takai D
  • Journal Title: Frontiers in Genetics Volume: 4 Pages: 275-275
• [Journal Article] Disruption of the expression and function of microRNAs in lung cancer as a result of epigenetic changes. (2013)
  • Author(s): Watanabe K, Takai D.
  • Journal Title: Frontiers in Genetics Volume: 4 Pages: 275-275
  • Peer Reviewed
• [Journal Article] Successful Treatment of Mediastinal Unicentric Castleman's Disease Using Video-Assisted Thoracoscopic Surgery with Preoperative Embolization. (2013)
  • Author(s): Amano Y, Takai D, Ohishi N, Shinozaki-Ushiku A, Fukayama M, Akahane M, Nakajima J, Nagase T.
  • Journal Title: Case Reports in Medicine Volume: 2013 Pages: 354507-354507
  • Peer Reviewed
• [Journal Article] Detection of novel paraja ring finger 2-fer tyrosine kinase mRNA chimeras is associated with poor postoperative prognosis in non-small cell lung cancer. (2013)
  • Author(s): Kawakami M, Ishikawa R, Amano Y, Sunohara M, Watanabe K, Ohishi N, Yatomi Y, Nakajima J, Fukayama M, Nagase T, Takai D.
  • Journal Title: Cancer Sci Volume: 104 Issue: 11 Pages: 1447-1454
  • DOI: 10.1111/cas.12250
  • Peer Reviewed
• [Journal Article] A pilot study of salvage irinotecan monotherapy for advanced biliary tract cancer. (2013)
  • Author(s): Sasaki T, Isayama H, Nakai Y, Takahara N, Satoh Y, Takai D, Kogure H, Yamamoto N, Hirano K, Tada M, Yatomi Y, Koike K.
  • Journal Title: Anticancer Research Volume: 33 Pages: 2619-2622
  • Peer Reviewed
• [Journal Article] High-grade Lung Adenocarcinoma With Fetal Lung-like Morphology: Clinicopathologic, Immunohistochemical, and Molecular Analyses of 17 Cases (2013)
  • Author(s): Morita S, Yoshida A, Goto A, Ota S, Tsuta K, Yokozawa K, Asamura H, Nakajima J, Takai D, Mori M, Oka T, Tamaru J, Itoyama S, Furuta K, Fukayama M, Tsuda H.
  • Journal Title: Am J Surg Pathol Volume: 37(6) Issue: 6 Pages: 924-932
  • DOI: 10.1097/pas.0b013e31827e1e83
  • Peer Reviewed
• [Journal Article] FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer. (2013)
  • Author(s): Kawakami M, Morita S, Sunohara M, Amano Y, Ishikawa R, Watanabe K, Hamano E, Ohishi N, Nakajima J, Yatomi Y, Nagase T, Fukayama M, Takai D.
  • Journal Title: International Journal of Clinical & Experimental Pathology Volume: 6 Pages: 598-612
  • Peer Reviewed
• [Journal Article] Combined Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Epidermal Growth Factor Receptor Mutation in a Female Patient Who Never Smoked. (2013)
  • Author(s): Yoshida Y, Ota S, Murakawa T, Takai D, Nakajima J.
  • Journal Title: Annals of Thoracic and Cardiovascular Surgery Volume: Epub ahead
  • NAID: 130003377861
  • Peer Reviewed
• [Journal Article] Growth-associated hyperphosphatemia in young recipients accelerates aortic allograft calcification in a rat model. (2013)
  • Author(s): Yamauchi Haruo
  • Journal Title: The Journal of Thoracic and Cardiovascular Surgery Volume: 145 Issue: 2 Pages: 522-530
  • DOI: 10.1016/j.jtcvs.2012.03.010
  • Peer Reviewed
• [Journal Article] Uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1) polymorphisms are associated with toxicity and efficacy in irinotecan monotherapy for refractory pancreatic cancer (2013)
  • Author(s): Takahara N, Nakai Y, Isayama H, Sasaki T, Satoh Y, Takai D, Miyabayashi K, Mohri D, Kawakubo K, Kogure H, Yamamoto N, Sasahira N, Hirano K, Ijichi H, Tada M, Yatomi Y, Koike K
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: 71 Issue: 1 Pages: 85-92
  • DOI: 10.1007/s00280-012-1981-0
  • Peer Reviewed
• [Journal Article] FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer (2013)
  • Author(s): Kawakami M, Morita S, Sunohara M, Amano Y, Ishikawa R, Watanabe K, Hamano E, Ohishi N, Nakajima J, Yatomi Y, Nagase T, Fukayama M, Takai D
  • Journal Title: International Journal of Clinical and Experimental Pathology Volume: 6 Pages: 598-612
  • Peer Reviewed
• [Journal Article] High-grade lung adenocarcinoma with fetal-lung-like morphology ? Clinicopathological, immunohistochemical, and molecular analyses of 17 cases (2013)
  • Author(s): Morita S, Yoshida A, Goto A, Ota S, Tsuta K, Yokozawa K, Asamura H, Nakajima J, Takai D, Mori M, Oka T, Tamaru J, Itoyama S, Furuta K, Fukayama M, Tsuda H
  • Journal Title: American Journal of Surgical Pathology Volume: in press
  • Peer Reviewed
• [Journal Article] Genome structure-based screening identified epigenetically silenced microRNA associated with invasiveness in non-small-cell lung cancer (2012)
  • Author(s): Watanabe K, Emoto N, Hamano E, Sunohara M, Kawakami M, Kage H, Kitano K, Nakajima J, Goto A, Fukayama M, Nagase T, Yatomi Y, Ohishi N, Takai D
  • Journal Title: Int J Cancer Volume: 130(11) Pages: 2580-2590
• [Journal Article] Pulmonary Venous Invasion, Determined by Chest Computed Tomographic Scan, as a Potential Early Indicator of Zygomycosis Infection : A Case Series (2012)
  • Author(s): Kitagawa H, Watanabe K, Kage H, Inoh S, Goto A, Fukayama M, Nagase T, Ohishi N, Takai D
  • Journal Title: J Thorac Imaging Volume: 27(4)
• [Journal Article] Analysis for the combination expression of CK20, FABP1 and MUC2 is sensitive for the prediction of peritoneal recurrence in gastric cancer (2012)
  • Author(s): Satoh Y, Mori K, Kitano K, Kitayama J, Yokota H, Sasaki H, Uozaki H, Fukayama M, Seto Y, Nagawa H, Yatomi Y, Takai D
  • Journal Title: Jpn J Clin Oncol Volume: 42(2) Pages: 148-152
• [Journal Article] Genome structure-based screening identifiedepigenetically silenced microRNA associated with invasiveness in non-small-cell lung cancer. (2012)
  • Author(s): Watanabe K, Goto A, Takai D.
  • Journal Title: Int J Cancer. Volume: 130 Issue: 11 Pages: 2580-2590
  • DOI: 10.1002/ijc.26254
  • Peer Reviewed
• [Journal Article] Pulmonary Venous Invasion, Determined by Chest Computed Tomographic Scan, as a Potential Early Indicator of Zygomycosis Infection: A Case Series (2012)
  • Author(s): Kitagawa H, Watanabe K, Kage H, Inoh S, Goto A, Fukayama M, Nagase T, Ohishi N, Takai D
  • Journal Title: J Thorac Imaging Volume: 27 Issue: 4 Pages: W97-W99
  • DOI: 10.1097/rti.0b013e3182282d17
  • Peer Reviewed
• [Journal Article] Analysis for the combination expression of CK20, FABP1 and MUC2 is sensitive for the prediction of peritoneal recurrence in gastric cancer (2012)
  • Author(s): Satoh Y, Mori K, Kitano K, Kitayama J, Yokota H, Sasaki H, Uozaki H, Fukayama M, Seto Y, Nagawa H, Yatomi Y, Takai D
  • Journal Title: Jpnease Journal of Clinical Oncology Volume: 42 Issue: 2 Pages: 148-152
  • DOI: 10.1093/jjco/hyr179
  • Peer Reviewed
• [Journal Article] Analysis for the combination expression of CK20, FABP1 and MUC2 is sensitive for the prediction of peritoneal recurrence in gastric cancer (2012)
  • Author(s): Satoh Y, Takai D, et al.
  • Journal Title: Jpn J Clin Oncol. Volume: 42 Issue: 2 Pages: 148-152
  • DOI: 10.1093/jjco/hyr204
  • Peer Reviewed
• [Journal Article] Suppression of Tgf・1 in lung alveolar epithelium-derived cells using adeno-associated virus type 2/5 vectors to carry short hairpin RNA (2011)
  • Author(s): Kage H, Sugimoto K, Sano A, Kitagawa H, Nagase T, Ohishi N, Takai D
  • Journal Title: Experimental Lung Research Volume: 37(3) Pages: 175-185
• [Journal Article] Polymerase reaction without primers throughout for the reconstruction of full-length cDNA from products of rapid amplification of cDNA ends (RACE) (2011)
  • Author(s): Sunohara M, Kawakami M, Kage H, Watanabe K, Emoto N, Nagase T, Ohishi N, Takai D
  • Journal Title: Biotechnol Lett Volume: 33(7) Pages: 1301-1307
• [Journal Article] CpG island methylation of microRNAs is associated with tumor size and recurrence of non-small-cell lung cancer (2011)
  • Author(s): Kitano K, Watanabe K, Emoto N, Kage H, Hamano E, Nagase T, Sano A, Murakawa T, Nakajima J, Goto A, Fukayama M, Yatomi Y, Ohishi N, Takai D
  • Journal Title: Cancer Sci Volume: 102(12) Pages: 2126-2131
  • NAID: 10030245653
• [Journal Article] CpG island methylation of microRNAs is associated with tumor size and recurrence of non-small-cell lung cancer (2011)
  • Author(s): Kitano K, Watanabe K, Emoto N, Kage H, Hamano E, Nagase T, Sano A, Murakawa T, Nakajima J, Goto A, Fukayama M, Yatomi Y, Ohishi N, Takai D.
  • Journal Title: Cancer Sci Volume: 102 Issue: 12 Pages: 2126-2131
  • DOI: 10.1111/j.1349-7006.2011.02101.x
  • NAID: 10030245653
  • Peer Reviewed
• [Journal Article] Polymerase reaction without primers throughout for the reconstruction of full-length cDNA from products of rapid amplification of cDNA ends (RACE) (2011)
  • Author(s): Sunohara M, Takai D, et al.
  • Journal Title: Biotechnol Lett. Volume: 33 Issue: 7 Pages: 1301-1307
  • DOI: 10.1007/s10529-011-0580-1
  • Peer Reviewed
• [Journal Article] Suppression of transforming growth factor β1 in lung alveolar epithelium-derived cells using adeno-associated virus type 2/5 vectors to carry short hairpin RNA (2011)
  • Author(s): Kage H, Takai D, et al.
  • Journal Title: Exp Lung Res. Volume: 37 Issue: 3 Pages: 175-185
  • DOI: 10.3109/01902148.2010.529985
  • Peer Reviewed
• [Presentation] Loss of PABPN1 and alternative polyadenylation yield poor prognosis in non-small cell lung cancer (2014)
  • Author(s): Ichinose J, Watanabe K, Sano A, Nagase T, Nakajima J, Fukayama M, Yatomi Y, Ohishi N, Takai D
  • Organizer: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Can lung cancer with overexpression of RET-proto oncogene be a good candidate for vandetanib treatment? (2014)
  • Author(s): Sunohara M, Morita S, Kawakami M, Watanabe K, Kage H, Amano Y, Ishikawa R, Fukayama M, Nagase T, Ohishi N, Takai D
  • Organizer: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Histone methylation-mediated silencing of mir-139 enhances an aggressive phenotype of non-small cell lung cancer (2014)
  • Author(s): Watanabe K, Sunohara M, Amano Y, Ishikawa R, Ichinose J, Nakajima J, Fukayama M, Yatomi Y, Nagase T, Ohishi N, Takai D
  • Organizer: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Loss of PABPN1 and alternative polyadenylation yield poor prognosis in non-small cell lung cancer. (2014)
  • Author(s): Ichinose J, Watanabe K, Sano A, Nagase T, Nakajima J, Fukayama M, Yatomi Y, Ohishi N, Takai D
  • Organizer: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Can lung cancer with overexpression of RET-proto oncogene be a good candidate for vandetanib treatment ? (2014)
  • Author(s): Sunohara M, Morita S, Kawakami M, Watanabe K, Kage H, Amano Y, Ishikawa R, Fukayama M, Nagase T, Ohishi N, Takai D
  • Organizer: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Histone methylation-mediated silencing of mir-139 enhances an aggressive phenotype of non-small cell lung cancer. (2014)
  • Author(s): Watanabe K, Sunohara M, Amano Y, Ishikawa R, Ichinose J, Nakajima J, Fukayama M, Yatomi Y, Nagase T, Ohishi N, Takai D
  • Organizer: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Genome sturucture-based screeening identified epigenetically silenced microRNA associated with invasiveness in non-small cell lung cancer (2012)
  • Author(s): Watanabe K, Takai D, et al.
  • Organizer: AACR-IASLC Joint Conference on THE MOLECULAR ORIGINS OF LUNG CANCER
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2012-01-10
• [Presentation] CpG island methylation of microRNAs is associated with tumor size and the recurrence of non-small cell lung cancer (2012)
  • Author(s): Kitano K, Takai D, et al.
  • Organizer: AACR-IASLC Joint Conference on THE MOLECULAR ORIGINS OF LUNG CANCER
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2012-01-09
• [Presentation] CpG island methylation of microRNAs is associated with tumor size and the recurrence of non-small cell lung cancer (2012)
  • Author(s): Kitano K, Goto A, Fukayama M, Watanabe K, Emoto N, Kage H, Hamano H, Nagase T, Sano A, Murakawa T, Nakajima J, Yatomi Y, Ohishi N, Takai D
  • Organizer: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Genome structure-based screening identified epigenetically silenced microRNA associated with invasiveness in non-small cell lung cancer (2012)
  • Author(s): Watanabe K, Goto A, Fukayama M, Nagase T, Emoto N, Hamano E, Amano Y, Ishikawa R, Sunohara M, Kawakami M, Kitano K, Nakajima J, Yatomi Y, Ohishi N, Takai D
  • Organizer: AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Vandetanib Can Overcome the Acquired Resistance to Gefitinib Due to RET Overexpression in Lung Cancer (2012)
  • Author(s): Sunohara M, Kawakami K, Watanabe K, Morita S, Kage H, Amano Y , Fukayama M, Nagase T, N. Ohishi N, Takai D
  • Organizer: The 24th EORTC-NCI-AACR Symposium on 'Molecular Targets and Cancer Therapeutics
  • Place of Presentation: Dublin, Island
• [Presentation] Identification of FER as a New Molecular Target in Non-small Cell Lung Cancer (2012)
  • Author(s): Kawakami M, Sunohara M, Amano Y, Ishikawa R, Watanabe K, Hamano E, Ohishi N, Nagase T, Yatomi Y, Takai D
  • Organizer: The 24th EORTC-NCIAACR Symposium on 'Molecular Targets and Cancer Therapeutics
  • Place of Presentation: Dublin, Island
• [Presentation] Identification of FER as a New Molecular Target in Non-small Cell Lung Cancer (2012)
  • Author(s): Kawakami M, Sunohara M, Amano Y, Ishikawa R, Watanabe K, Hamano E, Ohishi N, Nagase T, Yatomi Y, Takai D
  • Organizer: The 24th EORTC-NCI-AACR Symposium on ‘Molecular Targets and Cancer Therapeutics'
  • Place of Presentation: Dublin, Ireland
• [Presentation] Vandetanib Can Overcome the Aquired Resistance to Gefitinib Due to RET Overexpression in Lung Cancer (2012)
  • Author(s): Sunohara M, Kawakami M, Watanabe K, Morita S, Kage H, Amano Y, Fukayama M, T. Nagase T, Ohishi N, Takai D
  • Organizer: The 24th EORTC-NCI-AACR Symposium on ‘Molecular Targets and Cancer Therapeutics'
  • Place of Presentation: Dublin, Ireland
• [Presentation] Crosstalk Between Alveolar Epithelial Cells And Fibroblasts Through Transforming Growth Factor ・1 And Prostaglandin Synthase 2 Results In Suppression Of Fibroblast Growth (2011)
  • Author(s): Kage H, Amano Y, Ishikawa R, Sunohara M, Kawakami M, Emoto N, Watanabe K, Hamano E, Ohishi N, Nagase T, Takai D
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: Denver, CO, USA
• [Remarks]
  • URL: http://kokyuki.umin.jp/305.html
• [Remarks]
  • URL: http://kokyuki.umin.jp/305.html