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Development of novel targeted therapy for esophageal squamous cell carcinoma

Research Project

Project/Area Number 20K16434
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

ZHENG LING  筑波大学, 医学医療系, 助教 (70833565)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords食道扁平上皮癌 / THG-1 / リン酸化 / グルタミン代謝 / 扁平上皮癌
Outline of Research at the Start

これまでの大規模ゲノム解析により食道扁平上皮癌では、特定ドライバー変異が高頻度で発見されておらず、早期診断マーカー、分子標的治療法が確立されていない予後不良の悪性腫瘍である。治療成績の向上および予後の改善のために、食道扁平上皮癌の発症機序の解明や早期診断のバイオマーカーの開発が求められている。申請者は食道扁平上皮癌細胞において過剰に発現する新規がん遺伝子THG-1の分子機能をリン酸化機能解析を中心に明らかにし、食道扁平上皮癌の早期診断、及び分子標的治療など臨床への応用を目指す。

Outline of Final Research Achievements

Esophageal squamous cell carcinoma is a cancer that is difficult to diagnose at an early stage and is prone to recurrence after surgery, lymph node metastasis, and invasion into adjacent organs. Therefore, further understanding of the mechanisms by which specific target molecules are involved in the progression is important to improve treatment and prognosis. In this project, we investigated the molecular function of THG-1, an oncogene highly expressed in esophageal squamous cell carcinoma, focusing on the phosphorylation of THG-1, with the aim of developing new molecularly targeted therapies for esophageal squamous cell carcinoma. We found that phosphorylated THG-1 induces changes in glutamine metabolism in squamous cell carcinomas, and we also found compounds that inhibit the changes in glutamine metabolism.

Academic Significance and Societal Importance of the Research Achievements

食道癌は主に扁平上皮癌と腺癌を含む二つの組織型に分類することができるが、アジアで特に多いのが扁平上皮癌である。食道扁平上皮癌に高発現し、さらに癌の進行に関わる分子であるTHG-1についてリン酸化機能解析を中心に解明した分子機構の理解及び特異的な標的分子の探索は、治療および予後の改善のために重要である。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (1 results)

All 2021

All Journal Article (1 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] Polyvinyl alcohol scaffolds and supplementation support 3D and sphere culturing of human cancer cell lines by reducing apoptosis and promoting cellular proliferation2021

    • Author(s)
      Okita Yukari、Zheng Ling、Kawanishi Kunio、Miyoshi Hirotoshi、Yanagihara Kazuyoshi、Kato Mitsuyasu
    • Journal Title

      Genes to Cells

      Volume: 26(5) Issue: 5 Pages: 336-343

    • DOI

      10.1111/gtc.12843

    • Related Report
      2020 Research-status Report
    • Peer Reviewed

URL: 

Published: 2020-04-28   Modified: 2023-01-30  

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