Cancer therapeutic target identification by comprehensive kinase profiling

• Project/Area Number: 24501363
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Wakayama Medical University (2014); Shizuoka Cancer Center Research Institute (2012-2013)
• Principal Investigator: KOH Yasuhiro 和歌山県立医科大学, 医学部, 講師 (80426519)
• Co-Investigator(Renkei-kenkyūsha): YAMAMOTO Nobuyuki 和歌山県立医科大学, 医学部, 教授 (60298966) ; YASUI Hirofumi 静岡県立静岡がんセンター, 副院長 ; NAKAJIMA Takashi 静岡県立静岡がんセンター, 病理診断科, 部長 (20124422) ; KONDO Haruhiko 杏林大学, 呼吸器・甲状腺外科, 教授 (60399590) ; ENDO Masahiro 静岡県立静岡がんセンター, 画像診断科, 部長 ; BOKU Narikazu 国立がん研究センター中央病院, 副院長 (50505948)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 分子標的治療 / チロシンキナーゼ / スキルス胃がん / 肺がん

Outline of Final Research Achievements

In this project, we incorporated peptide microarray system to evaluate the kinase activities of cancer cells and tissues for novel therapeutic targets and predictive biomarker identification.
Kinase activity signature specific to scirrhous-type gastric cancer were successfully identified using non-scirrhous and scirrhous gastric cancer cell lines according to basal kinase activities of tyrosine kinases. Moreover scirrhous gastric cancer cells were sensitive to multikinase inhibotors. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib, erlotinib and afatinib were compared using EGFR-mutant and –negative cell lines and inhibition profiles turned out to be very different among three inhibitors. In clinical study using tumor and normal tissues from small-cell lung cancer patients, novel therapeutic targets were successfully identified. Src inhibition was suggested to be novel therapeutic strategy for small-cell lung cancer.

Research Products

• [Journal Article] Prospective genetic profiling of squamous cell lung cancer and adenosquamous carcinoma in Japanese patients by multitarget assays. (2014)
  • Author(s): Hirotsugu Kenmotsu
  • Journal Title: BMC Cancer Volume: 14 Issue: 1 Pages: 786-786
  • DOI: 10.1186/1471-2407-14-786
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of actionable mutations in malignant pleural mesothelioma (2014)
  • Author(s): Takehito Shukuya
  • Journal Title: Lung Cancer Volume: 86 Issue: 1 Pages: 35-40
  • DOI: 10.1016/j.lungcan.2014.08.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mutant allele frequency predicts the efficacy of EGFR-TKIs in lung adenocarcinoma harboring the L858R mutation (2014)
  • Author(s): Akira Ono
  • Journal Title: Annals of Oncology Volume: 25 Issue: 10 Pages: 1948-1953
  • DOI: 10.1093/annonc/mdu251
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Changes in forced expiratory volume in 1 second over time in patients with controlled asthma at baseline (2014)
  • Author(s): Kazuto Matsunaga
  • Journal Title: Respiratory Medicine Volume: 108 Issue: 7 Pages: 976-982
  • DOI: 10.1016/j.rmed.2014.04.014
  • Peer Reviewed
• [Journal Article] Multiplexed molecular profiling of lung cancer using pleural effusion (2014)
  • Author(s): Hiroaki Akamatsu
  • Journal Title: Journal of Thoracic Oncology Volume: 9 Issue: 7 Pages: 1048-1052
  • DOI: 10.1097/jto.0000000000000203
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Assessment of mutational profile of Japanese lung adenocarcinoma patients by multitarget assays: A prospective, single-institute study (2014)
  • Author(s): Masakuni Serizawa
  • Journal Title: Cancer Volume: in press Issue: 10 Pages: 1471-1481
  • DOI: 10.1002/cncr.28604
  • Peer Reviewed
• [Journal Article] Molecular profiling of small cell lung cancer in a Japanese cohort. (2014)
  • Author(s): Kazushige Wakuda
  • Journal Title: Lung Cancer Volume: 84 Issue: 2 Pages: 139-144
  • DOI: 10.1016/j.lungcan.2014.02.013
  • Peer Reviewed
• [Journal Article] Biological significance of 18F-FDG uptake on PET in patients with non-small-cell lung cancer. (2014)
  • Author(s): Kaira K, Serizawa M, Koh Y, Takahashi T, Yamaguchi A, Hanaoka H, Oriuchi N, Endo M, Ohde Y, Nakajima T, Yamamoto N.
  • Journal Title: Lung Cancer Volume: 83 Issue: 2 Pages: 197-204
  • DOI: 10.1016/j.lungcan.2013.11.025
  • Peer Reviewed
• [Journal Article] Detection of EGFR T790M mutation in plasma DNA from patients refractory to EGFR tyrosine kinase inhibitor. (2013)
  • Author(s): Sakai K
  • Journal Title: Cancer Sci Volume: 104 Issue: 6 Pages: 1198-204
  • DOI: 10.1111/cas.12411
  • Peer Reviewed
• [Journal Article] Genomic aberrations associated with erlotinib resistance in non-small cell lung cancer cells (2013)
  • Author(s): Masakuni Serizawa
  • Journal Title: Anticancer Research Volume: 33 Pages: 5223-5233
  • Peer Reviewed
• [Journal Article] Size-Based Isolation of Circulating Tumor Cells in Lung Cancer Patients Using a Microcavity Array System (2013)
  • Author(s): Masahito Hosokawa, Hirotsugu Kenmotsu, Yasuhiro Koh, Tomoko Yoshino, Takayuki Yoshikawa, Tateaki Naito, Toshiaki Takahashi, Haruyasu Murakami, Yukiko Nakamura, Asuka Tsuya, Takehito Shukuya, Akira Ono, Hiroaki Akamatsu, Reiko Watanabe, Sachiyo Ono, Keita Mori, Hisashige Kanbara, Ken Yamaguchi, Tsuyoshi Tanaka, Tadashi Matsunaga, Nobuyuki Yamamoto
  • Journal Title: PLoS ONE Volume: 8 Issue: 6 Pages: e67466-e67466
  • DOI: 10.1371/journal.pone.0067466
  • Peer Reviewed
• [Journal Article] Microcavity Array System for Size-Based Enrichment of Circu lating Tumor Cells from the Blood of Patients with Small-Cell Lung Cancer (2013)
  • Author(s): Masahito Hosokawa, Takayuki Yoshikawa, Ryo Negishi, Tomoko Yoshino, Yasuhiro Koh, Hirotsugu Kenmotsu, Tateaki Naito, Toshiaki Takahashi, Nobuyuki Yamamoto, Yoshihito Kikuhara, Hisashige Kanbara, Tsuyoshi Tanaka, Ken Yamaguchi. Tadashi Matsunaga
  • Journal Title: Analytical Chemistry Volume: 85 Issue: 12 Pages: 5692-5698
  • DOI: 10.1021/ac400167x
  • Peer Reviewed
• [Journal Article] A microarray-based gene expression analysis to identify diagnostic biomarkers for unknown primary cancer. (2013)
  • Author(s): Kurahashi, I., Fujita, Y., Arao, T., Kurata, T., Koh, Y., Sakai, K., Matsumoto, K., Tanioka, M., Takeda, K., Takiguchi, Y., Yamamoto, N., Tsuya, A., Matsubara, N., Mukai, H., Minami, H., Chayahara, N., Yamanaka, Y., Miwa, K., Takahashi, S., Takahashi, S., Nakagawa, K. and Nishio, K.
  • Journal Title: PloS one Volume: 8 Issue: 5 Pages: e63249-e63249
  • DOI: 10.1371/journal.pone.0063249
  • Peer Reviewed
• [Journal Article] The effect of CYP2C19 polymorphism on the safety, tolerability, and pharmacokinetics of tivantinib (ARQ 197): results from a phase I trial in advanced solid tumors (2013)
  • Author(s): Nobuyuki Yamamoto
  • Journal Title: Annals of Oncology Volume: 24 Issue: 6 Pages: 1653-1659
  • DOI: 10.1093/annonc/mdt014
  • Peer Reviewed
• [Journal Article] Rationale and Design of the Japan Molecular Epidemiology for Lung Cancer Study (2013)
  • Author(s): Kawaguchi T, Ando M, Ito N, Isa SI, Tamiya A, Shimizu S, Saka H, Kubo A, Koh Y, Matsumura A
  • Journal Title: Clin Lung Cancer Volume: 14 Issue: 5 Pages: 596-600
  • DOI: 10.1016/j.cllc.2013.03.001
  • Peer Reviewed
• [Journal Article] Combined treatment with erlotinib and a transforming growth factor-β type I receptor inhibitor effectively suppresses the enhanced motility of erlotinib-resistant non-small cell lung cancer cells (2013)
  • Author(s): Masakuni Serizawa
  • Journal Title: Journal of Thoracic Oncology Volume: 8 Issue: 3 Pages: 259-69
  • DOI: 10.1097/jto.0b013e318279e942
  • Peer Reviewed
• [Journal Article] The Impact of Clinical Outcomes According to EGFR Mutation Status in Patients with Locally Advanced Lung Adenocarcinoma Who Recieved Concurrent Chemoradiotherapy (2013)
  • Author(s): Hiroaki Akamatsu
  • Journal Title: American Journal of Clinical Oncology Volume: Epub ahead of print Issue: 2 Pages: 144-147
  • DOI: 10.1097/coc.0b013e31826e04f9
  • Peer Reviewed
• [Presentation] BevacizumabとEGFR-TKIとの併用: Erlotinib+Bevacizumab vs Erlotinibのrandomized phaseⅡ studyの経験から (2014)
  • Author(s): 山本信之
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-11-14 – 2014-11-16
  • Invited
• [Presentation] 肺癌における遺伝子プロファイリング (2013)
  • Author(s): 釼持広知
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: 東京
• [Presentation] 肺腺癌における個別化医療の推進を目的とした体細胞変異プロファイリング (2013)
  • Author(s): 芹澤昌邦
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: 東京
• [Presentation] 胸水・心嚢水を用いた、胸部悪性腫瘍における網羅的分子プロファイリングの検討 (2013)
  • Author(s): 赤松弘朗
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: 東京
• [Presentation] 肺扁平上皮癌における遺伝子プロファイリングの検討 (2013)
  • Author(s): 釼持広知
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: 東京
• [Presentation] 次世代シーケンサーによる肺腺癌切除例の遺伝子プロファイルと病理組織像との検討 (2013)
  • Author(s): 井坂光宏
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: 東京
• [Presentation] 小細胞肺癌の分子プロファイリングの検討 (2013)
  • Author(s): 和久田一茂
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: 東京
• [Presentation] Prospective mutational characterization of Japanese patients with non-small-cell lung cancer using surgically resected tumor specimens by next-generation sequencing (2013)
  • Author(s): Yasuhiro Koh
  • Organizer: Markers in Cancer
  • Place of Presentation: Brussels
• [Presentation] Identification of actionable mutations in surgically resected tumor specimens from Japanese patients with non-small cell lung cancer by ultra-deep targeted sequencing (2013)
  • Author(s): Yasuhiro Koh
  • Organizer: American Society of Clinical Oncology annual meeting
  • Place of Presentation: Chicago
• [Presentation] In vitro tyrosine kinase activity profiling to identify molecular targets and predictive biomarkers in gastric cancer cell lines (2013)
  • Author(s): Yasuhiro Koh
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Washington DC
• [Presentation] In vitro tyrosine kinase activity profiling to identify molecular targets and predictive biomarkers in gastric cancer cell lines (2013)
  • Author(s): Yasuhiro Koh
  • Organizer: AACR annual meeting 2013
  • Place of Presentation: ワシントンDC（米国）
• [Presentation] Development of novel systems for the detection of circulating tumor cells in Japan (2012)
  • Author(s): 洪 泰浩
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Invited
• [Book] 変化を厭わない (2014)
  • Author(s): 山本信之
  • Total Pages: 1
  • Publisher: 呼吸と循環
• [Book] がん分子標的治療 腫瘍の遺伝子情報の臨床への応用 (2014)
  • Author(s): 洪 泰浩
  • Total Pages: 115
  • Publisher: メディカルレビュー社