Comprehensive genomic analysis of small cell lung cancer exploring mechanisms of the proliferation and therapeutic targets

• Project/Area Number: 24300346
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: National Cancer Center Japan
• Principal Investigator: GOTO Koichi 独立行政法人国立がん研究センター, 東病院, 科長 (90435719)
• Co-Investigator(Kenkyū-buntansha): UMEMURA Shigeki 国立がん研究センター, 東病院, 医員 (80623967) ; TSUCHIHARA Katsuya 国立がん研究センター, 早期/探索臨床研究センター, 分野長 (00415514) ; ISHII Genichiro 国立がん研究センター, 東病院・臨床開発センター, ユニット長 (00270869) ; ESUMI Hiroyasu 国立がん研究センター, 東病院, 院長 (70160364)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000); Fiscal Year 2014: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2012: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: 小細胞肺がん / 全エクソン解析 / SNPアレイ / 候補遺伝子 / 臨床情報 / 網羅的 / 予後不良 / PI3K/AKT/mTOR経路 / 小細胞肺癌 / カタログ情報

Outline of Final Research Achievements

The mechanisms of the proliferation of small cell lung cancer (SCLC) is not well identified. We conducted a comprehensive genomic analysis in both surgical resected and advanced SCLC cases and found a high penetrance of genetic alterations in the PI3K/AKT/mTOR pathway. These alterations were mutually exclusive with alterations in MYC family members which were reported to play a role in SCLC biology. Additionally, PIK3CA silencing induced a decrease in the proliferation of H1048 cells harboring activating mutation in PIK3CA gene. These results suggested the biological importance of PI3K/AKT/mTOR pathway in the proliferation of SCLC.

Research Products

• [Journal Article] Therapeutic Priority of the PI3K/AKT/mTOR Pathway in Small Cell Lung Cancers as Revealed by a Comprehensive Genomic Analysis. (2014)
  • Author(s): Umemura S, Mimaki S, Makinoshima H, Tada S, Ishii G, Ohmatsu H, Niho S, Yoh K, Matsumoto S, Takahashi A, Morise M, Nakamura Y, Ochiai A, Nagai K, Iwakawa R, Kohno T, Yokota J, Ohe Y, Esumi H, Tsuchihara K, Goto K.
  • Journal Title: J Thorac Oncol Volume: 9(9) Issue: 9 Pages: 1324-31
  • DOI: 10.1097/jto.0000000000000250
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Therapeutic priority of the PI3K/AKT/mTOR pathway in small cell lung cancers as revealed by a comprehensive genomic analysis (2014)
  • Author(s): Shigeki Umemura, et al.
  • Journal Title: Journal of thoracic oncology Volume: -
  • Peer Reviewed
• [Presentation] Comprehensive genomic analysis of small cell lung cancer in Asian patients (2013)
  • Author(s): Shigeki Umemura
  • Organizer: American Society of Clinical Oncology Annual meeting 2013
  • Place of Presentation: シカゴ（米国）
• [Presentation] Comprehensive genomic analysis of small cell lung cancer in Asian patients (2013)
  • Author(s): 梅村茂樹
  • Organizer: 第72回 日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 小細胞肺がんにおけるdriver mutationの検索 (2013)
  • Author(s): 梅村茂樹
  • Organizer: 第54回 日本肺癌学会総会
  • Place of Presentation: 東京
• [Presentation] 小細胞肺癌の網羅的遺伝子変異解析による治療標的の探索 (2012)
  • Author(s): 梅村茂樹
  • Organizer: 第53回日本肺癌学会総会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2012-11-09