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

2013 Fiscal Year Final Research Report

• 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
• Keywords: 肺がん / チロシンキナーゼ

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] 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
• [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
• [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
• [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) Pages: W97-99
• [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] 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
• [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
  • Year and Date: 20140106-09
• [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
  • Year and Date: 20140106-09
• [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
  • Year and Date: 20140106-09
• [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
  • Year and Date: 20121106-09
• [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
  • Year and Date: 20121106-09
• [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
  • Year and Date: 20120108-11
• [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
  • Year and Date: 20120108-11
• [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
  • Year and Date: 20110513-18
• [Remarks]
  • URL: http://kokyuki.umin.jp/305.html