• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of combined immune-oncology therapy targeting immune checkpoint for castration-resistant prostate cancer

Research Project

Project/Area Number 17K11128
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionKanazawa University

Principal Investigator

KONAKA Hiroyuki  金沢大学, 医学系, 協力研究員 (40334768)

Co-Investigator(Kenkyū-buntansha) 角野 佳史  金沢大学, 医学系, 准教授 (10397218)
泉 浩二  金沢大学, 附属病院, 講師 (80646787)
北川 育秀  金沢大学, 医学系, 協力研究員 (00452102)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords去勢抵抗性前立腺癌 / 再燃メカニズム / 免疫チェックポイント分子 / クロストーク / 前立腺癌 / 腫瘍免疫 / シグナル伝達系 / NF-κB / 複合がん免疫療法 / 免疫チェックポイント
Outline of Final Research Achievements

The strong effect of androgen-deprivation therapy may become severely compromised when the prostate cancer cells develop into a castration-resistant stage. Although blockade of androgen-androgen receptor signaling inhibited prostate cancer cell proliferation, metastatic ability of prostate cancer cells increases. In lymph node metastasis that is problematic in castration-resistant stage, blockade of androgen-androgen receptor signaling activates NF-κB and TNF-α, inducing subsequent CCR7 upregulation resulting in cell migration via p38 activation. Regarding taxane-resistance in castration-resistant stage, p38 and STAT3 activation, downstream of NF-κB, were activated with CCL2 secretion. CCL2 contributed taxane-resistance in the autocrine manner.

Academic Significance and Societal Importance of the Research Achievements

CRPCのリンパ節転移内で前立腺癌細胞がさらなる転移能を獲得するメカニズムの一つとして、NF-κB→TNF-α→CCR7→p38の活性化経路が関与する可能性が示唆された。また、CRPCの治療であるタキサン系薬剤の耐性化にも、NF-κBの活性化が関与していることが明らかにされており、の下流であるp38とSTAT3の活性化が関与することがあきらかになった。さらにタキサン耐性株で著しく分泌亢進するCCL2は自己分泌作用でタキサン耐性に寄与している。CCL2-CCR2経路の遮断はPD-1阻害薬の効果を著しく改善することが報告されており、CRPCについても極めて有望な治療となる可能性が示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (1 results)

All 2018

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

  • [Journal Article] Tumor necrosis factor-α induces prostate cancer cell migration in lymphatic metastasis through CCR7 upregulation.2018

    • Author(s)
      Maolake A, Izumi K, Natsagdorj A, Iwamoto H, Kadomoto S, Makino T, Naito R, Shigehara K, Kadono Y, Hiratsuka K, Wufuer G, Nastiuk KL, Mizokami A.
    • Journal Title

      Cancer science

      Volume: 109 Issue: 5 Pages: 1524-1531

    • DOI

      10.1111/cas.13586

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi