Biomarker development research for early response evaluation of immune checkpoint inhibitors in NSCLC using liquid biopsy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15545
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Mitsumura Takahiro 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (10833270)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Liquid biopsy / lung cancer

Outline of Final Research Achievements

In this study, we analyzed the correlation between changes in the proportion of mutated genes (Variant Allele Frequency; VAF) obtained through blood-based liquid biopsy conducted before and during treatment initiation and imaging evaluation before treatment initiation and at each observation point, in cases of non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). The results revealed that changes in VAF correlated more strongly with changes in tumor diameter at 24 weeks post-treatment initiation than with early tumor diameter changes. Furthermore, the group with decreased VAF showed tumor shrinkage at 24 weeks compared to the group without decreased VAF, a phenomenon not observed during the early stages of treatment.

Free Research Field

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Academic Significance and Societal Importance of the Research Achievements

ICIはその作用機序から、従来の化学療法と同様の画像評価が難しい場合がある。体液を用いたリキッドバイオプシーは低侵襲で行うことが可能であり、特に血液中のcirculating tumor DNAの定量的なモニタリングを治療の効果判定に用いることが期待されている。
本研究の結果は、ICIを投与したNSCLCにおいて早期の画像評価が困難な症例においても、リキッドバイオプシーが治療の有効性の判定に有用である可能性を示唆している。ICIの有効性と予後に関する予測精度を高めるためには更なる研究が不可欠であるものの、今回の結果が、ICIの効果判定法の開発の一助となると考えられる。