Comprehensive analysis of druggable tyrosine kinase in idiopathic interstitial pneumonia

• Project/Area Number: 16K15458
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Okayama University
• Principal Investigator: Kiura Katsuyuiki 岡山大学, 大学病院, 教授 (10243502)
• Co-Investigator(Kenkyū-buntansha): 大橋 圭明 岡山大学, 大学病院, 講師 (60729193) ; 久保 寿夫 岡山大学, 大学病院, 助教 (90726928)
• Research Collaborator: HIGO Hisao 岡山大学, 大学院医師薬学総合研究科, 大学院生
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肺線維症 / 特発性肺線維症 / 次世代シーケンサー / Kinase遺伝子発現解析 / レーザーマイクロダイセクション / 臨床呼吸器学

Outline of Final Research Achievements

We performed comprehensive analysis in plumonary fibrosis to develop precision medicine.　We obtained 13 samples from 5 patients. 6 samples were from bilateral pneumotectomy. The gene expression profile was heterogeneous even in same patient. ERBB4 or PIM2 was overexpressed in some of our cases. These genes might be possible druggable target for pulmonary fibrosis.

Research Products

• [Journal Article] Second primary cancer in survivors of locally advanced non-small cell lung cancer treated with concurrent chemoradiation followed by surgery (2018)
  • Author(s): Makimoto Go、Kubo Toshio、Oze Isao、Ohashi Kadoaki、Hotta Katsuyuki、Tabata Masahiro、Soh Junichi、Toyooka Shinichi、Katsui Kuniaki、Takigawa Nagio、Tanimoto Mitsune、Kiura Katsuyuki
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 48 Pages: 287-290
  • DOI: 10.1093/jjco/hyy003
  • Peer Reviewed
• [Journal Article] MET or NRAS amplification is an acquired resistance mechanism to the third-generation EGFR inhibitor naquotinib. (2018)
  • Author(s): Ninomiya Kiichiro、Ohashi Kadoaki、Makimoto Go、Tomida Shuta、Higo Hisao、Kayatani Hiroe、Ninomiya Takashi、Kubo Toshio、Ichihara Eiki、Hotta Katsuyuki、Tabata Masahiro、Maeda Yoshinobu、Kiura Katsuyuki
  • Journal Title: Sci Rep. Volume: 8 Pages: 1955-1955
  • DOI: 10.1038/s41598-018-20326-z
  • Peer Reviewed / Open Access
• [Journal Article] Phase 3 study of ceritinib vs chemotherapy in ALK-rearranged NSCLC patients previously treated with chemotherapy and crizotinib (ASCEND-5): Japanese subset (2018)
  • Author(s): Kiura Katsuyuki、Imamura Fumio、Kagamu Hiroshi、Matsumoto Shingo、Hida Toyoaki、Nakagawa Kazuhiko、Satouchi Miyako、Okamoto Isamu、Takenoyama Mitsuhiro、Fujisaka Yasuhito、Kurata Takayasu、Ito Masayuki、Tokushige Kota、Hatano Ben、Nishio Makoto
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 48 Pages: 367-375
  • DOI: 10.1093/jjco/hyy016
  • Peer Reviewed
• [Journal Article] Osimertinib in patients with epidermal growth factor receptor T790M advanced non-small cell lung cancer selected using cytology samples (2018)
  • Author(s): Kiura Katsuyuki、Yoh Kiyotaka、Katakami Nobuyuki、Nogami Naoyuki、Kasahara Kazuo、Takahashi Toshiaki、Okamoto Isamu、Cantarini Mireille、Hodge Rachel、Uchida Hirohiko
  • Journal Title: Cancer Science Volume: 109 Pages: 1177-1184
  • DOI: 10.1111/cas.13511
  • Peer Reviewed
• [Journal Article] Randomized, Double-Blind Phase Ib/III Study of Erlotinib With Ramucirumab or Placebo in Previously Untreated EGFR -Mutant Metastatic Non-Small-Cell Lung Cancer (RELAY): Phase Ib Results (2018)
  • Author(s): Reck Martin、Garon Edward B.、Paz-Ares Luis、Ponce Santiago、Jaime Jesus Corral、Juan Oscar、Nadal Ernest、Kiura Katsuyuki、Widau Ryan C.、He Shuang、Dalal Rita、Lee Pablo、Nakagawa Kazuhiko
  • Journal Title: Clinical Lung Cancer Volume: 19
  • DOI: 10.1016/j.cllc.2017.11.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Phase II Study of Trastuzumab Emtansine in HER2-Positive Non-Small Cell Lung Cancer (2018)
  • Author(s): Hotta Katsuyuki、Aoe Keisuke、Kozuki Toshiyuki、Ohashi Kadoaki、Ninomiya Kiichiro、Ichihara Eiki、Kubo Toshio、Ninomiya Takashi、Chikamori Kenichi、Harada Daijiro、Nogami Naoyuki、Hirata Taizo、Hinotsu Shiro、Toyooka Shinichi、Kiura Katsuyuki
  • Journal Title: Journal of Thoracic Oncology Volume: 13 Pages: 273-279
  • DOI: 10.1016/j.jtho.2017.10.032
  • Peer Reviewed
• [Journal Article] A phase I trial of afatinib and bevacizumab in chemo-naive patients with advanced non-small-cell lung cancer harboring EGFR mutations: Okayama Lung Cancer Study Group Trial 1404 (2018)
  • Author(s): Ninomiya T, Nogami N, Kozuki T, Harada D, Kubo T, Ohashi K, Kuyama S, Kudo K, Bessho A, Fukamatsu N, Fujimoto N, Aoe K, Shibayama T, Sugimoto K, Takigawa N, Hotta K, Kiura K.
  • Journal Title: Lung Cancer Volume: 115 Pages: 103-108
  • DOI: 10.1016/j.lungcan.2017.11.025
  • Peer Reviewed
• [Journal Article] Potential influence of interleukin-6 on the therapeutic effect of gefitinib in patients with advanced non-small cell lung cancer harbouring EGFR mutations (2018)
  • Author(s): Tamura T, Kato Y, Ohashi K, Ninomiya K, Makimoto G, Gotoda H, Kubo T, Ichihara E, Tanaka T, Ichimura K, Maeda Y, Hotta K, Kiura K.
  • Journal Title: Biochem Biophys Res Commun Volume: 495 Pages: 360-367
  • DOI: 10.1016/j.bbrc.2017.10.175
  • Peer Reviewed
• [Journal Article] A phase II trial of carboplatin plus S-1 for elderly patients with advanced non-small-cell lung cancer with wild-type epidermal growth factor receptor: The Okayama Lung Cancer Study Group Trial 1202 (2017)
  • Author(s): Kuyama Shoichi、Ochi Nobuaki、Bessho Akihiro、Hotta Katsuyuki、Ikeda Genyo、Kishino Daizo、Kubo Toshio、Harada Daijiro、Fujimoto Nobukazu、Nakanishi Masamoto、Umeno Takahiro、Okada Toshiaki、Chikamori Kenichi、Yamagishi Tomoko、Ohashi Kadoaki、Ichihara Eiki、Takigawa Nagio、Tanimoto Mitsune、Kiura Katsuyuki
  • Journal Title: Lung Cancer Volume: 112 Pages: 188-194
  • DOI: 10.1016/j.lungcan.2017.08.010
  • Peer Reviewed
• [Journal Article] Clinical characteristics of Japanese candidates for lung transplant for interstitial lung disease and risk factors for early death while on the waiting list (2017)
  • Author(s): Higo Hisao、Kurosaki Takeshi、Ichihara Eiki、Kubo Toshio、Miyoshi Kentaroh、Otani Shinji、Sugimoto Seiichiro、Yamane Masaomi、Miyahara Nobuaki、Kiura Katsuyuki、Miyoshi Shinichiro、Oto Takahiro
  • Journal Title: Respiratory Investigation Volume: 55 Pages: 264-269
  • DOI: 10.1016/j.resinv.2017.03.002
  • Peer Reviewed
• [Journal Article] Ceritinib versus chemotherapy in patients with ALK -rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial (2017)
  • Author(s): Shaw Alice T、Kim Tae Min、Crino Lucio、Gridelli Cesare、Kiura Katsuyuki、Liu Geoffrey、Novello Silvia、Bearz Alessandra、Gautschi Oliver、Mok Tony、Nishio Makoto、Scagliotti Giorgio、Spigel David R、Deudon Stephanie、Zheng Cheng、Pantano Serafino、Urban Patrick、Massacesi Cristian、et al.
  • Journal Title: The Lancet Oncology Volume: 18 Pages: 874-886
  • DOI: 10.1016/s1470-2045(17)30339-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Triplet therapy with afatinib, cetuximab, and bevacizumab induces deep remission in lung cancer cells harboring EGFR T790M in vivo (2017)
  • Author(s): Kudo K, Ohashi K, Makimoto G, Higo H, Kato Y, Kayatani H, Kurata Y, Takami Y, Minami D, Ninomiya T, Kubo T, Ichihara E, Sato A, Hotta K, Yoshino T, Tanimoto M, Kiura K.
  • Journal Title: Molecular Oncology Volume: Epub Pages: 670-681
  • DOI: 10.1002/1878-0261.12063
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ceritinib in patients with advanced, crizotinib-treated, anaplastic lymphoma kinase-rearranged NSCLC: Japanese subset (2017)
  • Author(s): Hida Toyoaki、Satouchi Miyako、Nakagawa Kazuhiko、Seto Takashi、Matsumoto Shingo、Kiura Katsuyuki、Nokihara Hiroshi、Murakami Haruyasu、Tokushige Kota、Hatano Ben、Nishio Makoto
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 47 Pages: 618-624
  • DOI: 10.1093/jjco/hyx045
  • Peer Reviewed
• [Journal Article] Three-Year Follow-Up of an Alectinib Phase I/II Study in ALK-Positive Non-Small-Cell Lung Cancer: AF-001JP (2017)
  • Author(s): Tamura Tomohide、Kiura Katsuyuki、Seto Takashi、Nakagawa Kazuhiko、Maemondo Makoto、Inoue Akira、Hida Toyoaki、Yoshioka Hiroshige、Harada Masao、Ohe Yuichiro、Nogami Naoyuki、Murakami Haruyasu、Kuriki Hiroshi、Shimada Tadashi、Tanaka Tomohiro、Takeuchi Kengo、Nishio Makoto
  • Journal Title: Journal of Clinical Oncology Volume: 35 Pages: 1515-1521
  • DOI: 10.1200/jco.2016.70.5749
  • Peer Reviewed
• [Journal Article] Endobronchial ultrasound-guided transbronchial needle aspiration of hilar and mediastinal lymph nodes detected on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (2016)
  • Author(s): Minami D, Takigawa N, Oda N, Ninomiya T, Kubo T, Ohashi K, Sato A, Hotta K, Tabata M, Kaji M, Tanimoto M, Kiura K..
  • Journal Title: Jpn J Clin Oncol. Volume: 46 Pages: 529-33
  • DOI: 10.1093/jjco/hyw023
  • Peer Reviewed
• [Journal Article] Development of a skin rash within the first week and the therapeutic effect in afatinib monotherapy for EGFR-mutant non-small cell lung cancer (NSCLC): Okayama Lung Cancer Study Group experience. (2016)
  • Author(s): Kudo K, Hotta K, Bessho A, Nogami N, Kozuki T, Kuyama S, Inoue K, Harita S, Okada T, Gemba K, Fujii M, Takigawa N, Oda N, Tanimoto M, Kiura K.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 77 Pages: 1005-9
  • DOI: 10.1007/s00280-015-2910-9
  • Peer Reviewed
• [Journal Article] Safety and discomfort during bronchoscopy performed under sedation with fentanyl and midazolam: a prospective study. (2016)
  • Author(s): Minami D, Takigawa N, Watanabe H, Ninomiya T, Kubo T, Ohashi K, Sato A, Hotta K, Tabata M, Tanimoto M, Kiura K.
  • Journal Title: Jpn J Clin Oncol. Volume: 46 Pages: 871-4
  • DOI: 10.1093/jjco/hyw083
  • Peer Reviewed
• [Journal Article] A phase II study of topotecan and cisplatin with sequential thoracic radiotherapy in elderly patients with small-cell lung cancer: Okayama Lung Cancer Study Group 0102. (2016)
  • Author(s): Kubo T, Fujiwara K, Hotta K, Okada T, Kuyama S, Harita S, Ninomiya T, Kamei H, Hosokawa S, Bessho A, Maeda T, Kozuki T, Fujimoto N, Ninomiya K, Takemoto M, Kanazawa S, Takigawa N, Tabata M, Tanimoto M, Ueoka H, Kiura K.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 78 Pages: 769-74
  • DOI: 10.1007/s00280-016-3135-2
  • Peer Reviewed
• [Journal Article] Potential influence of being overweight on the development of hepatic dysfunction in Japanese patients with EGFR-mutated non-small cell lung cancer undergoing gefitinib monotherapy: the Okayama Lung Cancer Study Group experience. (2016)
  • Author(s): Oda N, Hotta K, Yoshioka H, Kudo K, Ichihara E, Kato Y, Ninomiya K, Minami D, Ninomiya T, Kubo T, Ohashi K, Sato A, Takigawa N, Tabata M, Tanimoto M, Kiura K.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 78 Pages: 941-47
  • DOI: 10.1007/s00280-016-3146-z
  • Peer Reviewed
• [Presentation] Acquired resistance to the third-generation EGFR inhibitor ASP8273 is associated with MET or NRAS gene amplifications in preclinical models (2017)
  • Author(s): Kiichiro Ninomiya, Kadoaki Ohashi, Shuta Tomida, Hiroe Kayatani, Tomoki Tamura, Hisao Higo, Go Makimoto, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Katsuyuki Kiura.
  • Organizer: AACR Annual Meeting 2017
  • Int'l Joint Research
• [Presentation] A comprehensive analysis of autopsied specimens and patient-derived cell lines in ALK-positive lung cancers with rapid acquired resistance to alectinib (2017)
  • Author(s): Go Makimoto, Kadoaki Ohashi, Kazuya Nishii, Shuta Tomida, Hiroe Kayatani, Tomoki Tamura, Hisao Higo, Kiichiro Ninomiya, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Katsuyuki Kiura
  • Organizer: AACR Annual Meeting 2017
  • Int'l Joint Research
• [Presentation] Clinical Characteristics of Japanese Candidates for Lung Transplant Due to Interstitial Lung Disease and Risk Factors for Early Death While on the Waiting List (2017)
  • Author(s): Hisao Higo , Eiki Ichihara , Takeshi Kurosaki , Kentaroh Miyoshi , Toshio Kubo , Shinji Otani , Seiichiro Sugimoto , Masaomi Yamane , Nobuaki Miyahara , Katsuyuki Kiura , Takahiro Oto
  • Organizer: American Thoracic Society 2017 International Conference
  • Int'l Joint Research
• [Presentation] Second primary cancer in survivors of locally advanced NSCLC treated with concurrent chemoradiation followed by surgery. (2016)
  • Author(s): Go Makimoto, Toshio Kubo, Yuka Kato, Takashi Ninomiya, Isao Oze, Kadoaki Ohashi, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Nagio Takigawa, Shinichi Toyooka, Kuniaki Katsui, Mitsune Tanimoto, Katsuyuki Kiura
  • Organizer: 2016 ASCO Annual Meeting
  • Place of Presentation: Chicago
  • Year and Date: 2016-06-03
  • Int'l Joint Research
• [Presentation] Molecular Profiling of Idiopathic Pulmonary Fibrosis (2016)
  • Author(s): 肥後 寿夫、木浦 勝行
  • Organizer: 第2回 呼吸器基礎研究を加速するための若手研究会
  • Place of Presentation: 国立京都国際会館