Genome-wide analysis for the cure of advanced lung cancer

• Project/Area Number: 16K07128
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Aichi Medical University
• Principal Investigator: Kubo Akihito 愛知医科大学, 医学部, 教授 (60416245)
• Co-Investigator(Kenkyū-buntansha): 洪 泰浩 和歌山県立医科大学, 医学部, 准教授 (80426519)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 肺癌 / 中皮腫 / 長期生存 / 化学療法 / 次世代シーケンシング / 肺がん / ゲノムワイド解析 / 次世代シーケンス / 癌 / ゲノム / 遺伝子 / 薬剤反応性

Outline of Final Research Achievements

The aim of this study was to determine the clinical and molecular factors that lead to clinical “cure” in patients with “incurable” stage IV lung cancer or mesothelioma.
We identified 10 cases of such exceptional responders of stage IV lung cancer that showed marked response to chemotherapy and remained alive and long-term (2 years or longer) treatment-free and progression-free. Among these, 9 were lung cancer (small cell carcinoma 5, adenocarcinoma 3, and combined small and adenocarcinoma 1) and 1 was mesothelioma. Smokers accounted for 80%, most with heavy-smoking history. The results suggested of immune-related mechanism for the exceptional long-term remission, nearing to cure. Molecular profiling analyses are currently underway.

Academic Significance and Societal Importance of the Research Achievements

化学療法が著効し長期間無治療で寛解が維持されたIV期肺がんまたは中皮腫のイントリンシックな分子プロファイルの探索と化学療法の効果との関連を調べることにより、治癒につながりうる長期寛解の分子メカニズムの機序解明は、予後不良な進行肺がん・中皮腫に対する新たな治療戦略として大きな貢献が期待される。

Research Products

• [Int'l Joint Research] Natl Univ Health System & Cancer Inst(シンガポール)
• [Int'l Joint Research] Samsung Med Ctr, Sungkyunkwan Univ(韓国)
• [Int'l Joint Research] Chao Family Cancer Ctr, UC Irvine(米国)
• [Int'l Joint Research] Natl Univ Health System & Cancer Inst(シンガポール)
• [Int'l Joint Research] Samsung Med Ctr, Sungkyunkwan Univ(韓国)
• [Int'l Joint Research] Chao Family Cancer Ctr, UC Irvine(米国)
• [Int'l Joint Research] Natl Univ Health System & Cancer Inst(Singapore)
• [Int'l Joint Research] Samsung Med Ctr, Sungkyunkwan Univ(韓国)
• [Int'l Joint Research] Chao Family Cancer Ctr, UC Irvine(U.S.A.)
• [Int'l Joint Research] Natl Univ Health System & Cancer Inst(Singapore)
• [Int'l Joint Research] Samsung Med. Ctr, Sungkyunkwan Univ.(韓国)
• [Int'l Joint Research] Chao Family Cancer Ctr, UC Irvine(U.S.A.)
• [Journal Article] Impact of somatic mutations on prognosis in resected non‐small‐cell lung cancer: The Japan Molecular Epidemiology for lung cancer study (2020)
  • Author(s): Tamiya Akihiro、Koh Yasuhiro、Isa Shun‐ichi、Kubo Akihito、Ando Masahiko、Saka Hideo、Yoshimoto Naoki、Takeo Sadanori、Adachi Hirofumi、Tagawa Tsutomu、Kawashima Osamu、Yamashita Motohiro、Kataoka Kazuhiko、Takenoyama Mitsuhiro、Takeuchi Yukiyasu、Watanabe Katsuya、Matsumura Akihide、Kawaguchi Tomoya
  • Journal Title: Cancer Medicine Volume: 9 Issue: 7 Pages: 2343-2351
  • DOI: 10.1002/cam4.2897
  • Peer Reviewed / Open Access
• [Journal Article] Bicytopenia in Primary Lung Melanoma Treated with Nivolumab (2019)
  • Author(s): Takahashi Ayumu、Kubo Akihito、Mizuno Shohei、Kasai Kenji、Asai Nobuhiro、Yonezawa Toshiyuki、Kosaka Kenshi、Nishimura Masaki、Tanaka Hiroyuki、Yokoe Norihito、Tsuzuki Toyonori、Takami Akiyoshi、Yamaguchi Etsuro
  • Journal Title: Internal Medicine Volume: 58 Issue: 6 Pages: 827-831
  • DOI: 10.2169/internalmedicine.1011-18
  • NAID: 130007612113
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2019-03-15
  • Peer Reviewed / Open Access
• [Journal Article] Cost-utility analysis of aprepitant for patients who truly need it in Japan (2019)
  • Author(s): Tsukiyama Ikuto、Ando Masahiko、Tsukiyama Sumiyo、Takeuchi Masayuki、Ejiri Masayuki、Kurose Yusuke、Saito Hiroko、Arakawa Ichiro、Inoue Tadao、Yamaguchi Etsuro、Kubo Akihito
  • Journal Title: Supportive Care in Cancer Volume: Epub Issue: 10 Pages: 2243-51
  • DOI: 10.1007/s00520-019-04672-w
  • Peer Reviewed
• [Journal Article] Small cell lung cancer and interstitial pneumonia associated with anti‐transcriptional intermediary factor‐1γ‐positive dermatomyositis (2019)
  • Author(s): Kato Toshio、Ito Satoru、Tsuzuki Toyonori、Watanabe Daisuke、Kubo Akihito、Yamaguchi Etsuro
  • Journal Title: Respirology Case Reports Volume: 7 Issue: 4
  • DOI: 10.1002/rcr2.412
  • Peer Reviewed
• [Journal Article] CCR4 expression in tumor-infiltrating regulatory T cells in patients with squamous cell carcinoma of the lung: A prognostic factor for relapse and survival (2019)
  • Author(s): Kubo A, Asai N, Suzuki S, Murotani K, Numanami H, Yoshikawa K, Ueda R, Yamaguchi E
  • Journal Title: Cancer Invest Volume: 37 Issue: 3 Pages: 163-73
  • DOI: 10.1080/07357907.2019.1582848
  • Peer Reviewed
• [Journal Article] Cost-effectiveness of aprepitant in Japanese patients treated with cisplatin-containing highly emetogenic chemotherapy (2018)
  • Author(s): Tsukiyama Ikuto、Hasegawa Shiori、Ikeda Yoshiaki、Takeuchi Masayuki、Tsukiyama Sumiyo、Kurose Yusuke、Ejiri Masayuki、Sakuma Masaki、Saito Hiroko、Arakawa Ichiro、Inoue Tadao、Yamaguchi Etsuro、Kubo Akihito
  • Journal Title: Cancer Science Volume: 109 Issue: 9 Pages: 2881-2888
  • DOI: 10.1111/cas.13736
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of serum anti-GM-CSF autoantibody levels in autoimmune pulmonary alveolar proteinosis (2018)
  • Author(s): Nishimura Masaki、Yamaguchi Etsuro、Takahashi Ayumu、Asai Nobuhiro、Katsuda Eisuke、Ohta Toyohiro、Ohtsuka Yoshinori、Kosaka Kenshi、Matsubara Ayako、Tanaka Hiroyuki、Yokoe Norihito、Kubo Akihito、Konno Satoshi、Baba Kenji
  • Journal Title: Biomarkers in Medicine Volume: 12 Issue: 2 Pages: 151-159
  • DOI: 10.2217/bmm-2017-0362
  • Peer Reviewed
• [Journal Article] Association between environmental tobacco smoke exposure and the occurrence of EGFR mutations and ALK-rearrangements in never-smokers with non-small cell lung cancer: analyses from a prospective multinational ETS registry. (2017)
  • Author(s): Kubo A, Soo RA, Ando M, Kawaguchi T, Ahn MJ, Ou S-HI
  • Journal Title: Clin Lung Cancer Volume: 18 Issue: 5 Pages: 535-42
  • DOI: 10.1016/j.cllc.2017.01.005
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Multiplex Ultrasensitive Genotyping of Patients with Non-Small Cell Lung Cancer for Epidermal Growth Factor Receptor (EGFR) Mutations by Means of Picodroplet Digital PCR (2017)
  • Author(s): Watanabe Masaru、Kawaguchi Tomoya、Isa Shun-ichi、Ando Masahiko、Tamiya Akihiro、Kubo Akihito、Saka Hideo、Takeo Sadanori、Adachi Hirofumi、Tagawa Tsutomu、Kawashima Osamu、Yamashita Motohiro、Kataoka Kazuhiko、Ichinose Yukito、Takeuchi Yukiyasu、Watanabe Katsuya、Matsumura Akihide、Koh Yasuhiro
  • Journal Title: EBioMedicine Volume: 21 Pages: 86-93
  • DOI: 10.1016/j.ebiom.2017.06.003
  • Peer Reviewed / Open Access
• [Journal Article] PIK3CA mutation as a distinctive genetic feature of non-small cell lung cancer with chronic obstructive pulmonary disease: A comprehensive mutational analysis from a multi-institutional cohort (2017)
  • Author(s): Sawa Kenji、Koh Yasuhiro、Kawaguchi Tomoya、Kambayashi Satoshi、Asai Kazuhisa、Mitsuoka Shigeki、Kimura Tatsuo、Yoshimura Naruo、Yoshimoto Naoki、Kubo Akihito、Saka Hideo、Matsumura Akihide、Wanibuchi Hideki、Yamamoto Nobuyuki、Nishiyama Noritoshi、Hirata Kazuto
  • Journal Title: Lung Cancer Volume: 112 Pages: 96-101
  • DOI: 10.1016/j.lungcan.2017.07.039
  • Peer Reviewed / Open Access
• [Journal Article] Association between environmental tobacco smoke exposure and the occurrence of EGFR mutations and ALK-rearrangements in never-smokers with non-small cell lung cancer: analyses from a prospective multinational ETS registry (2017)
  • Author(s): Kubo A, Soo RA, Ando M, Kawaguchi T, Ahn MJ, Ou S-HI
  • Journal Title: Clin Lung Cancer (in press) Volume: -
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Interstitial Lung Disease after Pleurodesis for Malignant Pleural Effusion (2017)
  • Author(s): Yokoe Y, Katsuda E, Kosaka K, Hamanaka R, Matsubara A, Nishimura M, Tanaka H, Asai N, Takahashi A, Kawamura T, Ishiguchi T, Yamaguchi E, Kubo A
  • Journal Title: Internal Medicine (in press) Volume: -
  • NAID: 130005773833
  • Peer Reviewed / Open Access
• [Journal Article] The ATS/ERS/JRS/ALAT statement "IPF by HRCT" could predict acute exacerbation of interstitial pneumonia in non-small cell lung cancer (2017)
  • Author(s): Asai N, Katsuda E, Hamanaka R, Kosaka K, Matsubara A, Nishimura M, Tanaka H, Yokoe N, Takahashi A, Yamaguchi E, Kubo A
  • Journal Title: Tumori Volume: 103 Issue: 1 Pages: 60-65
  • DOI: 10.5301/tj.5000574
  • Peer Reviewed
• [Journal Article] Prospective analysis on oncogenic driver mutations and environmental factors: Japan Molecular Epidemiology for lung cancer study (JME) (2016)
  • Author(s): 2.Tomoya Kawaguchi, Yasuhiro Koh, Masahiko Ando, Norimasa Ito, Sadanori Takeo, Hirofumi Adachi, Tsutomu Tagawa, Seiichi Kakegawa, Motohiro Yamashita, Kazuhiko Kataoka, Yukito Ichinose, Yukiyasu Takeuchi, Masakuni Serizawa, Akihiro Tamiya, Shigeki Shimizu, Naoki Yoshimoto, Akihito Kubo, Shun-ichi Isa, Hideo Saka
  • Journal Title: J Clin Oncol Volume: 34 Issue: 19 Pages: 2247-2257
  • DOI: 10.1200/jco.2015.64.2322
  • Peer Reviewed / Open Access
• [Presentation] Diagnostic and prognostic impact of serum procalcitonin in non-small cell lung cancer. (2019)
  • Author(s): Kajikawa S, Ohashi W, Yonezawa T, Kosaka K, Kato T, Tanaka H, Ito S, Yamaguchi E, Kubo A.
  • Organizer: 24th Asian Pacific Society of Respirology. Hanoi, Vietnam. November 2019
  • Int'l Joint Research
• [Presentation] The safety assessment of crizotinib and alectinib from real-world data of 840 ALK-inhibitor naive patients with NSCLC harboring ALKrearrangement (WJOG9516L). (2019)
  • Author(s): Kunimasa K, Ito K, Yamanaka T, Fujimoto D, Mori M, Maeno K, Tomomatsu K, Tamura A, Tanaka H, Watanabe S, Teraoka S, Hataji O, Suzuki K, Hontsu S, Hara S, Bessho A, Kubo A, Okuno M, Nakagawa K, Yamamoto N.
  • Organizer: European Society of Medical Oncology (ESMO) Congress, Barcelona, Spain. September, 2019.
  • Int'l Joint Research
• [Presentation] Low detection rate of EGFR driver and T790M mutations in plasma by cobas EGFR Mutation Test v2 after acquired resistance to afatinib (2018)
  • Author(s): Oya Y, Yoshida T, Asada K, Oguri T, Inui N, Morikawa S, Ito K, Kimura T, Matsui T, Kubo A, Kato T, Shindo J, Tsuda T, Hida T
  • Organizer: International Association for Studying Lung Cancer (IASLC) Asia Conference on Lung Cancere 2018
  • Int'l Joint Research
• [Presentation] Impact of de novo T790M on outcome for resected NSCLC from EGFR mutant cohort of Japan Molecular Epidemiology (JME) study (2018)
  • Author(s): Matsumoto Y, Kawaguchi T, Sawa K, Watanabe M, Isa S-I, Ando M, Tamiya A, Kubo A, Saka H, Matsumura A, Koh Y
  • Organizer: 19th World Conference on Lung Cancer
  • Int'l Joint Research
• [Presentation] Impact of somatic mutations on recurrence free survival (RFS) and overall survival (OS) for resected non-small cell lung cancer (NSCLC): results from the Japan Molecular Epidemiology for lung cancer study (JME) (2018)
  • Author(s): Tamiya A, Koh Y, Kubo A, Ando M, Isa SI, Saka H, Yoshimoto N, Serizawa M, Takeo S, Adachi H, Tagawa T, Kawashima O, Yamashita M, Kataoka K, Ichinose Y, Takeuchi Y, Watanabe K, Matsumura A, Kawaguchi T
  • Organizer: Annual Meeting of the American Society of Clinical Oncology
  • Int'l Joint Research
• [Presentation] Cost-effectiveness analysis of aprepitant in Japanese patients who received high-dose cisplatin. (2018)
  • Author(s): Tsukiyama I, Hasegawa S, Ikeda Y, Takeuchi M, Tsukiyama S, Kurose Y, Ejiri M, Sakuma M, Saito H, Arakawa I, Inoue T, Yamaguchi E, Kubo A.
  • Organizer: Annual Meeting of the American Society of Clinical Oncology
  • Int'l Joint Research
• [Presentation] Impact of somatic mutations on recurrence free survival (RFS) and overall survival (OS) for resected non-small cell lung cancer (NSCLC): results from the Japan Molecular Epidemiology for lung cancer study (JME). (2018)
  • Author(s): Tamiya A, Koh Y, Kubo A, Ando M, Isa SI, Saka H, Yoshimoto N, Serizawa M, Takeo S, Adachi H, Tagawa T, Kawashima O, Yamashita M, Kataoka K, Ichinose Y, Takeuchi Y, Watanabe K, Matsumura A, Kawaguchi T.
  • Organizer: Annual Meeting of the American Society of Clinical Oncology
  • Int'l Joint Research
• [Book] 肺がん化学療法副作用マネジメント プロのコツ (2019)
  • Author(s): 加藤俊夫、久保昭仁
  • Total Pages: 396
  • Publisher: メジカルビュー
  • ISBN: 9784758318051
• [Book] 元気ホスピタル 最善の医療をめざして 愛知医科大学の最新医療 (2018)
  • Author(s): 久保昭仁
  • Total Pages: 213
  • Publisher: 南々社
  • ISBN: 9784864890786