Optimization of re-biopsy and liquid biopsy to detect mutations relevant to acquired resistance

• Project/Area Number: 17K07198
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Saga University
• Principal Investigator: Tomomi Nakamura 佐賀大学, 医学部, 助教 (90457490)
• Co-Investigator(Kenkyū-buntansha): 荒金 尚子 佐賀大学, 医学部, 准教授 (20321846) ; 佐藤 明美 佐賀大学, 医学部, 助教 (20568357) ; 渡邊 裕之 京都大学, 薬学研究科, 講師 (40710786) ; 木村 寛之 京都薬科大学, 薬学部, 准教授 (50437240)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: re-biopsy / liquid biopsy / T790M / テーラーメード治療 / EGFR-TKI / 獲得耐性機序 / 獲得耐性 / 再生検 / Liqud biopsy

Outline of Final Research Achievements

We performed a retrospective analysis of 22 patients with EGFR mutation-positive non-small cell lung cancer who exhibited 1st/2nd generation EGFR-TKI resistance to consider appropriate application of liquid and re-biopsy through analysis of current status in practice. T790M detection rate was 52% with re-biopsy and 58% with liquid biopsy. The concordance between tissue and plasma was 58%. Liquid biopsy reflects the whole body, whereas re-biopsy is useful for spatial diagnosis. In an effort to discover a noninvasive method for predicting cancer lesion harboring T790M mutation, we tried to develop SPECT imaging agents which selectively target the T790M positive EGFR. We completed mouse model which harbor T790M positive and negative metastatic lesions and tried to detect T790M
positive metastatic lesions by administration SPECT imaging agent. However, specific accumulation of SPECT imaging agents to tumor lesion could not been detected.

Academic Significance and Societal Importance of the Research Achievements

今回の検討から、治療薬の対象となる遺伝子変異を有する癌細胞が体内に存在するかという全身的な評価にはliquid biopsyが優れているが、どの病巣に治療の標的となる遺伝子変異が認められ、使用する薬剤にて縮小が期待できるかについては、現時点ではそれぞれの転移巣の組織再生検を行わないと判断が難しいことが確認された。今回の研究期間内には結果を出すことができなかったものの、放射線同位元素で標識した薬剤を投与後にSPECT撮影を行うことで目的とする遺伝子変異を有する病変を推定するという試みは、複数個所の再生検という侵襲をさけつつ治療効果を予測する点で期待がもたれる検査法ではないかと考えられた。

Research Products

• [Journal Article] Current Status and Problems of T790M Detection, a Molecular Biomarker of Acquired Resistance to EGFR Tyrosine Kinase Inhibitors, with Liquid Biopsy and Re-biopsy (2018)
  • Author(s): 5.Komiya K, Nakashima C, Nakamura T, Hirakawa H, Abe T, Ogusu S, Takahashi K, Takeda Y, Egashira Y, Kimura S, Sueoka-Aragane N
  • Journal Title: Anticancer Res Volume: 38 Issue: 6 Pages: 3559-3566
  • DOI: 10.21873/anticanres.12628
  • Peer Reviewed / Open Access
• [Presentation] 当院における液体生検と再生検の現状と問題点、その克服に向けて (2018)
  • Author(s): 小宮一利
  • Organizer: 第58回日本肺癌学会九州支部学術集会、第41回日本呼吸器内視鏡学会九州支部総会
• [Presentation] 液体生検と再生検はどのように使い分けるべきか？ (2018)
  • Author(s): 小宮一利
  • Organizer: 第58回日本呼吸器学会
• [Presentation] Correlation and problems of re-biopsy and liquid biopsy for detecting T790M mutation (2017)
  • Author(s): 小宮一利
  • Organizer: 第18回世界肺癌学会
  • Int'l Joint Research
• [Presentation] 当院におけるRe-biopsyの現状と問題点 (2017)
  • Author(s): 小宮一利
  • Organizer: 第15回臨床腫瘍学会