The strategies to overcome resistance to ALK inhibitor in lung cancer.

• Project/Area Number: 25462193
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Yokoi Sana 千葉県がんセンター(研究所), がんゲノムセンター, 部長 (30372452)
• Co-Investigator(Kenkyū-buntansha): Iizasa Toshihiko 千葉県がんセンター, 呼吸器外科, 部長 (10272303)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肺癌

Outline of Final Research Achievements

Anaplastic lymphoma kinase (ALK) which is one of the receptor tyrosine kinase is activated by chromosomal translocation and causes lung cancer (ALK lung cancer). ALK inhibitor shows remarkable effect for ALK lung cancer. However, ALK lung cancer becomes tolerance to ALK inhibitor in short time. To find a new therapeutic target for ALK lung cancer, the genomic abnormality was analyzed. As a result, we found a putative candidate gene which is decreased expression in ALK lung cancer by genomic deletion or DNA methylation in promoter region. A forced expression of this gene leads to the growth retardation in lung cancer cell line with ALK translocation.

Research Products

• [Journal Article] High CC chemokine receptor 7 expression improves postoperative prognosis of lung adenocarcinoma patients. (2013)
  • Author(s): Itakura M, Terashima Y, Shingyoji M, Yokoi S, Ohira M, Kageyama H, Matui Y, Yoshida Y, Ashinuma H, Moriya Y, Tamura H, Harigaya K, Matushima K, Iizasa T, Nakagawara A, Kimura H.
  • Journal Title: Br J Cancer. Volume: 109 Pages: 1100-1108
  • Peer Reviewed
• [Journal Article] Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma. (2013)
  • Author(s): Iuchi T, Shingyoji M, Sakaida T, Hatano K, Nagano O, Itakura M, Kageyama H, Yokoi S, Hasegawa Y, Kawasaki K, Iizasa T.
  • Journal Title: Lung Cancer Volume: 82 Pages: 282-287
  • Peer Reviewed
• [Presentation] 染色体転座により発現制御をされるALK関連分子の解析 (2015)
  • Author(s): 横井左奈、兼松宗太郎、近藤仁美、末永雄介、木村秀樹、飯笹俊彦
  • Organizer: 第62回日本臨床検査医学会学術集会
  • Place of Presentation: 岐阜市
  • Year and Date: 2015-11-19
• [Presentation] Frequent somatic mutations in neuroendocrine differentiation-related pathways in SCLC-transformed lung adenocarcinomas (2015)
  • Author(s): Yusyke Suenaga, Masato shingyoji, Mamoru Kato, Isao Kurosaka, Miki Ohira, Tishihiko Iizasa, Hiroki Nagase, Sana Yokoi
  • Organizer: 日本人類遺伝学会第60回大会
  • Place of Presentation: 東京都
  • Year and Date: 2015-10-14
• [Presentation] 染色体転座に伴ってゲノム・エピゲノム制御を受けるALK関連分子の解析 (2015)
  • Author(s): 横井左奈、兼松宗太郎、近藤仁美、大塚紀子、末永雄介、木村秀樹、飯笹俊彦
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-10-08
• [Presentation] Frequent somatic mutations in neuroendocrine differentiation-related pathways in SCLC-transformed lung adenocarcinomas (2015)
  • Author(s): Yusyke Suenaga,Masato shingyoji,Mamoru Kato,Isao Kurosaka,Miki Ohira,Tishihiko Iizasa,Hiroki Nagase,Sana Yokoi
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-10-08
• [Presentation] EBUS-TBNAを利用した小細胞肺癌におけるTopoisomeraseの発現に関する検討 (2015)
  • Author(s): 新行内雅斗、芦沼宏典、吉田泰司、石橋史博、田村創、松井由紀子、守屋康充、飯笹俊彦、横井左奈、中島崇裕、関根郁夫
  • Organizer: 日本呼吸器内視鏡学会
  • Place of Presentation: 東京都
  • Year and Date: 2015-06-12
• [Presentation] Novel cancer related gene in ALK-positive lung cancer (2013)
  • Author(s): 横井左奈、夏恩迪、木村秀樹、中村友紀、大平美紀、影山肇、池部大、杉山孝弘、伊丹真紀子、永瀬浩喜、飯笹俊彦
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Somatic mutation search using next-gen sequencing approach (2013)
  • Author(s): 影山肇、丸喜明、中村由紀、大平美紀、横井左奈、越川信子、片山稔、永瀬浩喜
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Targeted exome sequencing of cancer related genes in lung cancer (2013)
  • Author(s): 飯笹俊彦、横井左奈、守屋康充、丸喜明、大平美紀、影山肇、中村友紀、近藤仁美、夏恩迪、新行内雅斗、板倉明司、伊丹真紀子、吉野一郎、永瀬浩喜
  • Organizer: 第51回日本癌治療学会学術集会
  • Place of Presentation: 京都
• [Presentation] Whole-exome sequencing of human non-small cell lung cancers and matched metastases to analyze metastatic driver mutations (2013)
  • Author(s): Wataru Shintani, Sumitaka Hase, Kengo Sato, Toshihiko Iizasa, Sana Yokoi, and Yasubumi Sakakibara
  • Organizer: EMBL Conference Cancer Genomics
  • Place of Presentation: Heidelberg, Germany
• [Presentation] ALK融合遺伝子陽性肺癌におけるゲノム解析 (2013)
  • Author(s): 橫井 左奈, 木村 秀樹, 夏 恩迪，影山 肇、 大平 美紀, 池部 大, 杉山 孝弘、 伊丹 真紀子, 飯笹 俊彦
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 仙台
• [Book] 遺伝医学MOOK別冊 今さら聞けない遺伝医学 「がんのゲノム医学入門」 (2014)
  • Author(s): 横井 左奈
  • Total Pages: 193
  • Publisher: 株式会社 メディカルドゥ