Identification of novel targets in the treatment of lung cancer

• Project/Area Number: 26293318
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Okayama University
• Principal Investigator: Miyoshi Shinichiro 岡山大学, 医歯(薬)学総合研究科, 教授 (00190827)
• Co-Investigator(Kenkyū-buntansha): 豊岡 伸一 岡山大学, 医歯(薬)学総合研究科, 教授 (30397880) ; 宗 淳一 岡山大学, 大学病院, 講師 (90559890) ; 山本 寛斉 岡山大学, 大学病院, 助教 (40467733) ; 佃 和憲 岡山大学, 大学病院, 講師 (20346430) ; 阪口 政清 岡山大学, 医歯(薬)学総合研究科, 准教授 (70379840) ; 片山 博志 岡山大学, 医歯(薬)学総合研究科, 准教授 (90713975)
• Research Collaborator: SHIEN Kazuhiko ; SUZAWA Ken ; OHTSUKA Tomoaki
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2014: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: 肺癌 / HER2 / 遺伝子変異 / チロシンキナーゼ阻害剤 / 癌 / 外科

Outline of Final Research Achievements

Recent developments in the genomic characterization of tumors have contributed to novel therapeutic approaches, and some molecular-targeted therapies based on the genetic profiles of tumors have improved patient survival. Human epidermal growth factor 2 (HER2) is a member of the HER family containing four receptor tyrosine kinases. Recently, we have identified novel mutations in the transmembrane domain of HER2 in lung adenocarcinomas. In this study, we clarified that these mutations could be oncogenic alterations of lung cancer. We also investigated the efficacy of afatinib as a HER2-targeted therapy in these HER2 altered lung cancer cells. In addition, we clarified a novel HER2 binding protein cytokeratin 19 (KRT19), and investigated the impact of KRT19 and HER2 interactions in signal transduction pathways to decode their possible roles in oncogenesis.

Research Products

• [Journal Article] Interaction of cytokeratin 19 head domain and HER2 in the cytoplasm leads to activation of HER2-Erk pathway. (2016)
  • Author(s): Ohtsuka T, Sakaguchi M, Yamamoto H, Tomida S, Takata K, Shien K, Hashida S, Miyata-Takata T, Watanabe M, Suzawa K, Soh J, Youyi C, Sato H, Namba K, Torigoe H, Tsukuda K, Yoshino T, Miyoshi S, Toyooka S.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 39557-39557
  • DOI: 10.1038/srep39557
  • Peer Reviewed / Open Access
• [Journal Article] Antitumor effect of afatinib, as a human epidermal growth factor receptor 2-targeted therapy, in lung cancers harboring HER2 oncogene alterations (2016)
  • Author(s): Ken Suzawa, Shinichi Toyooka, Masakiyo Sakaguchi, Mizuki Morita, Hiromasa Yamamoto, Shuta Tomida, Tomoaki Ohtsuka, Mototsugu Watanabe, Shinsuke Hashida, Yuho Maki, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda and Shinichiro Miyoshi
  • Journal Title: Cancer Science Volume: 107 Issue: 1 Pages: 45-52
  • DOI: 10.1111/cas.12845
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] HER2陽性肺癌に対するafatinibの有効性 (2016)
  • Author(s): 枝園和彦
  • Organizer: 第1回肺癌バイオカンファレンス
  • Place of Presentation: 東京
  • Year and Date: 2016-09-24
• [Presentation] Cytokeratin 19 binds to HER2 and activates HER2 and its downstream signaling (2016)
  • Author(s): Tomoaki Ohtsuka, Masakiyo Sakaguchi, Shuta Tomida, Hiromasa Yamamoto, Katsuyoshi Takata, Shinsuke Hashida, Mototsugu Watanabe, Ken Suzawa, Yuho Maki, Junichi Soh, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
  • Organizer: Tenth AACR-JCA Joint Conference on Breakthroughs in Cancer Research: From Biology to Therapeutics
  • Place of Presentation: Maui, Hawaii, USA
  • Year and Date: 2016-02-16
  • Int'l Joint Research
• [Presentation] HER2関連肺癌に対するアファチニブの抗腫瘍効果 (2015)
  • Author(s): 諏澤 憲，豊岡 伸一，大塚 智昭，渡邉 元嗣，橋田 真輔，牧 佑歩，山本 寛斉，宗 淳一，岡田 真典，伊賀 徳周，三好健太郎，杉本誠一郎，山根 正修，大藤 剛宏，三好新一郎
  • Organizer: 第58回関西胸部外科学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2015-06-12
• [Presentation] Anti-tumor effect of afatinib, an irreversible EGFR/HER2 dual inhibitor, in lung cancers harboring HER2 oncogene (2015)
  • Author(s): Ken Suzawa, Shinichi Toyooka, Masakiyo Sakaguchi, Tomoaki Ohtsuka, Mototsugu Watanabe, Shinsuke Hashida, Yuho Maki, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: Philadelphia, PA, USA
  • Year and Date: 2015-04-18 – 2015-04-22
• [Presentation] Identification of a novel binding protein playing a critical role in HER2 activation in lung cancer cells (2015)
  • Author(s): Tomoaki Ohtsuka, Masakiyo Sakaguchi, Katsuyoshi Takata, Shinsuke Hashida, Mototsugu Watanabe, Ken Suzawa, Yuho Maki, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] Anti-tumor effect of afatinib, an irreversible EGFR/HER2 dual inhibitor, in lung cancers harboring HER2 oncogene (2015)
  • Author(s): Ken Suzawa, Shinichi Toyooka, Masakiyo Sakaguchi, Tomoaki Ohtsuka, Mototsugu Watanabe, Shinsuke Hashida, Yuho Maki, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] 新規HER2膜貫通部領域遺伝子変異の機能解析 (2014)
  • Author(s): 諏澤憲、阪口政清、山本寛斉、宗淳一、牧佑歩、橋田真輔、大塚智昭、渡邉元嗣、浅野博昭、佃和憲、三好新一郎、豊岡伸一
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27