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

Research Project

Project/Area Number 17K07198
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor diagnostics
Research InstitutionSaga 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 *help
¥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)
Keywordsre-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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [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-biopsy2018

    • 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

    • Related Report
      2018 Research-status Report
    • 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
    • Related Report
      2018 Research-status Report
  • [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
    • Related Report
      2018 Research-status Report
  • [Presentation] Correlation and problems of re-biopsy and liquid biopsy for detecting T790M mutation2017

    • Author(s)
      小宮一利
    • Organizer
      第18回世界肺癌学会
    • Related Report
      2017 Research-status Report
    • 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
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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