Exploring the drug resistance mechanism through cellular senescence in the tumor microenvironment in esophageal cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23924
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Keio University
• Principal Investigator: MATSUDA Satoru 慶應義塾大学, 医学部(信濃町), 助教 (30594725)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 食道癌 / 集学的治療 / 薬剤耐性

Outline of Final Research Achievements

Using clinical samples of esophageal cancer from biopsy, we conducted RNA sequence and compared the gene expression profile between responder and non-responders. As results, the mesenchymal gene signatures were upregulated in non-responders. For validation, the drug resistant esophageal squamous cell carcinoma cell lines were developed. Aiming to identify the new drug target, the high throughput drug screening will be conducted.
In terms of the role of cellular senescence in the drug resistance mechanism, TGFβ was found to induce senescence in the tumor microenvironment.

Free Research Field

食道癌

Academic Significance and Societal Importance of the Research Achievements

食道扁平上皮癌に対しては、手術、化学療法、放射線治療を組わせた集学的治療の効果向上が求められている中、化学療法の効果向上の糸口を捉えることができた。臨床検体の網羅的解析と、細胞株における薬剤スクリーニングを組み合わせることで、臨床現象とメカニズムをリンクさせることができたのは意義深い。
本結果を踏まえ、既存の薬物療法と併用することで効果向上を実現できる新規治療開発が進むことが期待される。