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Clinical Significance of Early VEGF-A Elevation Following Ramucirumab Based Chemotherapy in Gastric Cancer

Research Project

Project/Area Number 18K08720
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

WAKATSUKI Takeru  公益財団法人がん研究会, 有明病院 消化器化学療法科, 医長 (60443876)

Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords胃癌 / ラムシルマブ / 血管新生阻害剤 / SNPs / バイオマーカー / VEGF-A/VEGFR2経路の二重阻害療法 / 切除不能進行・再発胃癌 / VEGF-A / 血管新生因子 / 切除不能進行再発胃癌 / 二重阻害 / 抗VEGFR2抗体
Outline of Final Research Achievements

The aim of this study was to identify the SNPs which predict the patients whose plasma VEGF-A levels are high after ramucirumab administration. Forty-two patients were enrolled in this study with the median PFS and OS was 4.1 and 11.0 months, respectively. The SNPs, VEGFR2 rs10013228 A>G (p=0.055), rs11133360 T>C (p=0.017), and rs2071559 A>G (p=0.072), were associated with higher plasma VEGF-A levels early after ramucirumab administration, but none of them were associated with survival. Instead, the SNPs potentially associated with worse prognosis were VEGFR1 XX with HR 2.23, p=0.070 for PFS and HR 3.10, p=0.030 for OS, and VEGFR2 YY with HR 2.11, p=0.093 for PFS. In preclinical mouse model, the combination therapy of anti-VEGF-A antibody and anti-VEGFR2 antibody showed higher antitumor efficacy compared to each monotherapy. The ligand and receptor dual blockade using antibodies in angiogenesis may be a promising therapy, and clinical trials are currently being prepared.

Academic Significance and Societal Importance of the Research Achievements

VEGF-Aは血管新生の亢進だけでなく、腫瘍免疫の抑制にも関与することが明らかとなり、血管新生阻害剤は腫瘍免疫の改善にも貢献する。本研究で導かれた抗VEGF-A抗体/抗VEGFR2抗体併用によるVEGF-A/VEGFR2経路の二重阻害療法は、より高い血管新生阻害作用のみならず腫瘍免疫の改善も期待され、新たな治療選択肢として有望である。現在、新規医師主導治験実施の準備を行っている。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2024 2021 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Neutralization of the induced VEGF-A potentiates the therapeutic effect of an anti-VEGFR2 antibody on gastric cancer in vivo2021

    • Author(s)
      Mashima Tetsuo、Wakatsuki Takeru、Kawata Naomi、Jang Myung-Kyu、Nagamori Akiko、Yoshida Haruka、Nakamura Kenichi、Migita Toshiro、Seimiya Hiroyuki、Yamaguchi Kensei
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 15125-15125

    • DOI

      10.1038/s41598-021-94584-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Exploratory analysis of predictive marker for ramucirumab using a large-scale gene approach2024

    • Author(s)
      若槻尊
    • Organizer
      第96回日本胃癌学会総会
    • Related Report
      2023 Annual Research Report
  • [Patent(Industrial Property Rights)] VEGF-A/VEGFR2経路のdual inhibition療法、及びこれに使用する医薬組成物2018

    • Inventor(s)
      馬島哲夫、若槻尊
    • Industrial Property Rights Holder
      馬島哲夫、若槻尊
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2025-01-30  

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