Search for new biomarkers for mesenchymal circulating tumor cells using next-generation TelomeScan

• Project/Area Number: 18K07303
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Juntendo University
• Principal Investigator: Togo Shinsaku 順天堂大学, 医学部, 准教授 (80365634)
• Co-Investigator(Kenkyū-buntansha): 小見山 博光 順天堂大学, 医学部, 非常勤講師 (30348982)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 循環腫瘍細胞 / 肺がん / バイオマーカー / テロメスキャンOBP-401 / 上皮間葉転換 / PD-L1 / 肺癌 / 血中循環腫瘍細胞 / 治療奏功予測バイオマーカー / 早期癌判定バイオマーカー / 非侵襲的高感度測定 / テロメスキャン

Outline of Final Research Achievements

Circulating tumor cells (CTCs) can provide predictable information about the early diagnosis, prognosis and recurrence period in the various types of cancer. CTCs include a variety of subtypes with different functional characteristics. Epithelial-mesenchymal transition (EMT) is considered as an essential process in the metastatic cascade and acquiring chemoresistance. We established further high speed and sensitive CTCs detection system by using the TelomeScan and clarified CTCs with various phenotype including mesenchymal marker and PD-L1, the immuno-check point inhibitor response marker could be as useful and reliable clinical surrogate biomarkers to predict treatment-sensitivity/resistance and recurrence period. We also succussed to detect EML4-ALK mutation-CTC derived from the patient of NSCLC with EML4-ALK mutation to demonstrated detected CTC by TelomeScan was defiantly lung cancer cells revealed the drivers oncogene mutation.

Academic Significance and Societal Importance of the Research Achievements

本研究の目的は、血中循環癌細胞(CTC)検出システムであるテロメスキャン法を用い悪性度が高く従来法では検出が困難であった上皮間葉転換を起こしたCTC（EMT-CTC）、免疫チェックポイント阻害剤の奏功に関連するPD-L1を発現するPDL-1-CTCの定量が可能となった。非小細胞肺がんの早期診断から個別化医療に向けた革新的な手法であることを立証し、世界初の画期的な臨床応用システムの基盤形成を行った。薬事承認申請までを視野に入れた研究開発であり,テロメスキャンによるCTC検出法から,様々ながん患者のがん関連死亡の減少と生存期間の延長により、国民の生活に寄与することが期待される。

Research Products

• [Journal Article] Mesenchymal Characteristics and Predictive Biomarkers on Circulating Tumor Cells for Therapeutic Strategy (2020)
  • Author(s): Okabe Takahiro、Togo Shinsaku、Fujimoto Yuichi、Watanabe Junko、Sumiyoshi Issei、Orimo Akira、Takahashi Kazuhisa
  • Journal Title: Cancers Volume: 12 Issue: 12 Pages: 3588-3588
  • DOI: 10.3390/cancers12123588
  • Peer Reviewed / Open Access
• [Journal Article] Sensitive detection of viable circulating tumor cells using a novel conditionally telomerase-selective replicating adenovirus in non-small cell lung cancer patients. (2017)
  • Author(s): Togo S, Katagiri N, Namba Y, Tulafu M, Nagahama K, Kadoya K, Takamochi K, Oh S, Suzuki K, Sakurai F, Mizuguchi H, Urata Y, Takahashi K.
  • Journal Title: Oncotarget Volume: 4 Issue: 21 Pages: 16818-16818
  • DOI: 10.18632/oncotarget.16818
  • Peer Reviewed / Open Access / Acknowledgement Compliant