Genetic analysis of pulmonary neuroendocrine tumors

• Project/Area Number: 17K18393
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology; Tumor therapeutics
• Research Institution: National Cancer Center Japan
• Principal Investigator: Tomohiro Miyoshi 国立研究開発法人国立がん研究センター, 東病院, 医員 (60794485)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 肺神経内分泌腫瘍 / 遺伝子解析 / 神経内分泌腫瘍 / 定型カルチノイド / 非定型カルチノイド / 大細胞神経内分泌癌(LCNEC) / 小細胞肺癌(SCLC) / 遺伝子プロファイル / 治療標的遺伝子 / 標的治療

Outline of Final Research Achievements

Pulmonary neuroendocrine tumors are defined as typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma (LCNEC), and small cell lung cancer (SCLC). Molecular biology and the mechanism of tumor progression have not been unclear. Because there are few treatment options for neuroendocrine lung tumors, the development of new molecularly targeted drugs is crucial to improve the prognosis of the patients. In the present study, we have analyzed the genetics of LCNEC and combined LCNEC with non-small cell lung cancer (NSCLC) by analyzing each component separately. We conducted a study to systematically determine the pathogenesis of pulmonary neuroendocrine tumors and to develop new molecular targets therapy. The genomic profile of LCNEC was similar to that of SCLC. Genetic alterations of the individual components in combined LCNEC were closely related despite their distinct morphologic appearances.

Academic Significance and Societal Importance of the Research Achievements

神経内分泌肺腫瘍については、既存の殺細胞性抗癌剤を上回る有効な治療標的の解明は十分とは言えない．肺神経内分泌腫瘍は治療の選択肢が少なく，新規の分子標的薬剤の開発が予後の改善に極めて重要であり，ここに重大なアンメット・ メディカル・ニーズがある存在する．本知見は，神経内分泌腫瘍の分子生物学的な発生機序の解明に有用な手がかりとなるものと考えられる．

Research Products

• [Journal Article] Ground-glass opacity is a strong prognosticator for pathologic stage IA lung adenocarcinoma. (2019)
  • Author(s): Miyoshi T, Aokage K, Katsumata S, Tane K, Ishii G, Tsuboi M.
  • Journal Title: Ann Thorac Surg. Volume: 印刷中 Issue: 1 Pages: 249-255
  • DOI: 10.1016/j.athoracsur.2019.01.079
  • Peer Reviewed
• [Journal Article] Stapling cartridge lavage cytology in limited resection for pulmonary malignant tumors: assessment of cytological status of the surgical margin. (2019)
  • Author(s): Miyoshi T, Yoshida J, Aokage K, Tane K, Ishii G, Tsuboi M.
  • Journal Title: Heliyon. Volume: 5 Issue: 2 Pages: e01240-e01240
  • DOI: 10.1016/j.heliyon.2019.e01240
  • Peer Reviewed / Open Access
• [Journal Article] Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung (2017)
  • Author(s): Miyoshi T, Umemura S, Matsumura Y, Mimaki S, Tada S, Makinoshima H, Ishii G5, Udagawa H, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Aokage K, Hishida T, Yoshida J, Nagai K, Goto K, Tsuboi M, Tsuchihara K.
  • Journal Title: Clini Cancer Res Volume: 23 Issue: 3 Pages: 757-765
  • DOI: 10.1158/1078-0432.ccr-16-0355
  • Peer Reviewed
• [Journal Article] Treatment approach for large-cell neuroendocrine carcinoma of the lung using next-generation sequencing (2017)
  • Author(s): Shigeki Umemura, Tomohiro Miyoshi, Genichiro Ishii, Katsuya Tsuchihara
  • Journal Title: Translational Cancer Research Volume: 6 Issue: S2 Pages: S448-S449
  • DOI: 10.21037/tcr.2017.03.51
• [Presentation] THE PROGNOSTIC SIGNIFICANCE OF GROUND-GLASS OPACITY ON CHEST CT AND LEPIDIC GROWTH COMPONENT IN PATIENTS WITH PATHOLOGICAL STAGE IA NON-SMALL CELL LUNG CANCER (2018)
  • Author(s): Tomohiro Miyoshi, Keiju Aokage, Shinya Katsumata, MD, Kenta Tane, Genichiro Ishii, Masahiro Tsuboi
  • Organizer: the 26th European Conference on General Thoracic Surgery, Ljubljana, Slovenia
  • Int'l Joint Research