Elucidation of the genetic mechanisms of post-CRT recurrence of esophageal cancer and the implementability of panel-based ctDNA evaluation.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17202
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Kyushu University
• Principal Investigator: MOTOMURA YUSHI 九州大学, 大学病院, 助教 (00826365)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 化学放射線治療 / 抵抗性特異的癌遺伝子変異 / リキッドバイプシー

Outline of Final Research Achievements

As a preliminary study for evaluation using circulating tumor DNA in liquid biopsy for comprehensive evaluation of genetic abnormalities causing resistance to chemoradiotherapy in esophageal squamous cell carcinoma, including treatment-reistant subclones. We identified mutated genes specific for treatment sensitivity (e.g., EP300) and resistance (e.g., NOTCH1), and reported that amplification of MYC is a founder event in recurrence after CRT for esophageal cancer (Hirata H, Motomura Y. et al. Cancer Res , 2021). In addition, focusing on the immune microenvironment, RNA-seq analysis between the sensitive and insensitive groups showed that the expression of genes related to immune checkpoints and immune exhaustion varied.

Free Research Field

放射線治療

Academic Significance and Societal Importance of the Research Achievements

切除不能食道癌に対して、化学放射線治療は確立された治療ではあるものの再発する症例も多く、未だに予後不良である。今回の食道癌の遺伝子解析の結果、MYC遺伝子の遺伝子増幅が治療抵抗性につながる原因として明らかになった。RNA発現解析では、免疫チェックポイント関連遺伝子の遺伝子発現レベルによって、治療の効果が分かれる可能性が示され、免疫チェックポイント阻害薬など、免疫を標的とした治療の有効性について検討する一助となり得る。