Establishment of personalized treatment for BIM deletion polymorphism-positive lung cancer using circulating tumor cells

• Project/Area Number: 18K08189
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Toho University
• Principal Investigator: Isobe Kazutoshi 東邦大学, 医学部, 准教授 (70385607)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: EGFR遺伝子変異陽性非小細胞肺癌 / オシメルチニブ / BIM-γ / 循環腫瘍細胞 / EGFR遺伝子変異 / BIM / BIM遺伝子多型 / 耐性遺伝子 / 原発性肺癌 / 非小細胞肺癌

Outline of Final Research Achievements

A prospective study was conducted to clarify the relationship between the response rate of osimertinib in EGFR mutation-positive non-small cell lung cancer and the mRNA expression level of BIM-γ in circulating tumor cells. Circulating tumor cells were harvested using the ClearCell FX system and subjected to quantitative real-time PCR. The response rate of osimertinib was lower in the BIM-γ high expression group (n = 15) than in the BIM-γ low expression group (n = 15) (26% vs. 73.3%, p = 0.011). It was suggested that overexpression of BIM-γ mRNA in circulating tumor cells of patients with EGFR mutation-positive non-small cell lung cancer could be a poor prognostic factor for osimertinib.

Academic Significance and Societal Importance of the Research Achievements

本研究は血液検体を用いた確実なサンプリングに基づいた個別化治療のシステム構築を目的にしており、得られた結果はBIM-γのmRNAの発現量を層別化因子とした原発性肺癌の個別化治療法の確立に大きく貢献するもので、本研究は非常に特色のある研究であると同時にその社会的意義も大きい。

Research Products

• [Journal Article] Quantification of BIM mRNA in circulating tumor cells of osimertinib-treated patients with EGFR mutation-positive lung cancer. (2021)
  • Author(s): Isobe K, Yoshizawa T, Sekiya M, Miyoshi S, Nakamura Y, Urabe N, Isshiki T, Sakamoto S, Takai Y, Tomida T, Adachi-Akahane S, Iyoda A, Homma S, Kishi K.
  • Journal Title: Respir Investig Volume: in press Issue: 4 Pages: 535-544
  • DOI: 10.1016/j.resinv.2021.03.010
  • Peer Reviewed / Open Access
• [Journal Article] Clinical importance of long non coding RNA LINC00460 expression in EGFR mutant lung adenocarcinoma. (2020)
  • Author(s): Nakano Y, Isobe K, Kobayashi H, Kaburaki K, Isshiki T, Sakamoto S, Takai Y, Tochigi N, Mikami T, Iyoda A, Homma S, Kishi K.
  • Journal Title: Int J Oncol. Volume: 56 Pages: 243-257
  • DOI: 10.3892/ijo.2019.4919
  • Peer Reviewed / Open Access
• [Journal Article] Clinical importance of Bcl-2-like 11 deletion polymorphism in idiopathic pulmonary fibrosis. (2019)
  • Author(s): Isobe K, Issiki T, Sakamoto S, Sano G, Takai Y, Tochigi N, Homma S.
  • Journal Title: J Thorac Dis. Volume: 11 Issue: 7 Pages: 2981-2989
  • DOI: 10.21037/jtd.2019.07.25
  • Peer Reviewed / Open Access
• [Presentation] Quantification of BIM mRNA In Circulating Tumor Cells Of Osimertinib-treated Patients with EGFR Mutation-positive Lung Cancer (2021)
  • Author(s): Kazutoshi Isobe, Hiroshi Kobayashi, Takuma Isshiki, Susumu Sakamoto, Yujiro Takai, Taichiro Tomida, Satomi Adachi-Akahane, Kazuma Kishi
  • Organizer: 2020 Wold Conference of Lung Cancer
  • Int'l Joint Research
• [Presentation] EGFR遺伝子変異陽性肺癌における循環腫瘍細胞中のBIM-RNA発現の検討 (2020)
  • Author(s): 磯部和順、小林 紘、吉澤孝浩、一色琢磨、坂本 晋、高井雄二郎、冨田太一郎、赤羽悟美、岸 一馬
  • Organizer: 第61回日本肺癌学会学術集会
• [Presentation] Clinical Importance of Long Noncoding RNA LINC00460 Expression in Plasma Cell-Free Tumor RNA in EGFR-Mutant Adenocarcinoma (2019)
  • Author(s): Kazutoshi Isobe, Yuta Nakano,Hiroshi Kobayashi, Kyohei Kaburaki Go Sano, Susumu Sakamoto, Yujiro Takai, Naobumi Tochigi, Tetsuo Mikami, Akira Iyoda and Sakae Homma
  • Organizer: American society of clinical oncology 2019 annual meeting.
  • Int'l Joint Research
• [Presentation] EGFR変異陽性肺腺癌における血漿遊離DNA中の長鎖非コードRNA発現の検討 (2019)
  • Author(s): 磯部和順、小林 紘、一色琢磨、坂本 晋、高井雄二郎、栃木直文、岸 一馬
  • Organizer: 日本肺癌学会学術集会
• [Presentation] Quantification of PD-L1 mRNA Expression in EGFR-mutant Lung Adenocarcinoma (2018)
  • Author(s): Isobe K, Kakimoto A, Kaburaki K, Kobayashi H, Sano G, Sakamoto S, Takai Y, Tochigi N, Mikami T, Iyoda A, Homma H
  • Organizer: European Society for Medical Oncology (ESMO) 2018 Congress
  • Int'l Joint Research
• [Presentation] Survival Effect of Long Intergenic Non-Protein Coding RNA 460 Expression in EGFR-Mutant Adenocarcinoma. (2018)
  • Author(s): Nakano Y, Isobe K, Kakimoto A, Kobayashi H, Kaburaki K, Sano G, Sakamoto S, Takai Y, Tochigi N, Mikami T, Iyoda A, Homma S
  • Organizer: European Society for Medical Oncology (ESMO) 2018 Congress
  • Int'l Joint Research
• [Presentation] 特発性肺線維症におけるＢＣＬ2Ｌ11遺伝子多型とレドックスの検討． (2018)
  • Author(s): 磯部和順、一色琢磨、鏑木教平、卜部尚久、伊藤貴文、澤田哲郎、佐野 剛、坂本 晋、高井雄二郎、栃木直文、本間 栄
  • Organizer: 第58回日本呼吸器学会学術講演会
• [Presentation] EGFR遺伝子変異陽性肺腺癌における血漿遊離DNA中のBIMmRNA発現の検討 (2018)
  • Author(s): 磯部和順、鏑木教平、小林 紘、中野雄太、 佐野 剛、坂本 晋、高井雄二郎、柿本篤志、 栃木直文、本間 栄
  • Organizer: 第59回日本肺癌学会学術集会
• [Patent(Industrial Property Rights)] EGFR遺伝子変異陽性非小細胞肺癌の検出法 (2019)
  • Inventor(s): 磯部 和順
  • Industrial Property Rights Holder: 磯部 和順
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019
  • Acquisition Date: 2020