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Investigation of personalized medicine for melanoma and mechanism of drug resistance using circulating tumor cells.

Research Project

Project/Area Number 16K10149
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionShinshu University

Principal Investigator

Kiniwa Yukiko  信州大学, 学術研究院医学系, 准教授 (20436893)

Co-Investigator(Kenkyū-buntansha) 奥山 隆平  信州大学, 学術研究院医学系, 教授 (80292332)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords悪性黒色腫 / 循環腫瘍細胞 / 病期 / 分子標的治療薬 / 体細胞変異 / 分子標的治療 / 免疫チェックポイント阻害薬 / 遺伝子変異 / BRAF遺伝子 / メラノーマ / PD1抗体薬 / CTLA抗体薬 / 分子標的薬 / 癌遺伝子 / 腫瘍特異的免疫応
Outline of Final Research Achievements

In this study, circulating tumor cells (CTCs) from melanoma patients were analyzed. CTCs were detected from the early stage, suggesting that CTCs may be provided from primary tumors as well as metastasis. In addition, number of CTCs changed with disease progression/remission during target therapies. Further, CTCs showed heterogenous somatic mutations. For example, CTCs from a patients with BRAF K601E revealed BRAF V600E and V600A as well as K601E. Our study clarified that CTCs are an important indicator of the potential for poor prognosis, treatment response, and disease recurrence.

Academic Significance and Societal Importance of the Research Achievements

本研究ではCTCの多様性を示すとともに,個別化医療の標的となる体細胞変異を検出できる可能性を示した.また,分子標的治療の治療効果と相関することが示され,治療効果予測のバイオマーカーとしても有用であるとともに,血液は転移病巣にくらべて採取しやすいため治療薬の選択にも役立つ.解析手法の複雑性が課題であり,より簡便で迅速な解析方法の開発が望まれる.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] 免疫チェックポイント阻害薬を中止後に、ダカルバジンを使用したメラノーマの3例2019

    • Author(s)
      中村謙太, 芦田敦子, 木庭 幸子, 奥山 隆平
    • Journal Title

      Skin Cancer

      Volume: 33 Pages: 196-200

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Type 1 Diabetes in a Melanoma Patient Treated with Ipilimumab after Nivolumab. .2018

    • Author(s)
      Omodaka T, Kiniwa Y, Sato Y, Suwa M, Sato M, Yamaguchi T, Sato A, Miyake T, Okuyama R.
    • Journal Title

      J Dermatol

      Volume: 45

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Presence of antibodies to striated muscle and acetylcholine receptor in association with occurrence of myasthenia gravis with myositis and myocarditis in a patient with melanoma treated with an anti-PD-1 antibody.2018

    • Author(s)
      Shirai T, Kiniwa Y, Sato R, Sano T, Nakamura K, Mikoshiba Y, Ohashi N, Sekijima Y, okuyama R.
    • Journal Title

      Eur J Cancer

      Volume: 106 Pages: 193-195

    • DOI

      10.1016/j.ejca.2018.10.025

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diversity of circulating tumor cells in peripheral blood: Detection of heterogeneous BRAF mutations in a patient with advanced melanoma by single-cell analysis2018

    • Author(s)
      Kiniwa Y, Nakamura K, Mikoshiba A, Akiyama Y, Morimoto A, Okuyama R
    • Journal Title

      J Dermatol Sci

      Volume: 90 Issue: 2 Pages: 211-216

    • DOI

      10.1016/j.jdermsci.2018.01.011

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 悪性黒色腫の病態と遺伝子異常;治療への新しい扉2018

    • Author(s)
      木庭幸子
    • Organizer
      第117回日本皮膚科学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] BRAF変異メラノーマに対する、BRAF阻害薬、TLR7アゴニスト、PD-1阻害薬の併用療法の解析2018

    • Author(s)
      中村謙太、谷口智憲, 村田眞志, 太田陽介, 木庭幸子, 河上裕, 奧山隆平
    • Organizer
      第9回最新皮膚疾患研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] BRAF/MEK阻害薬投与中に筋肉内膿瘍をきたした1例2018

    • Author(s)
      木庭幸子
    • Organizer
      メラノーマ分子標的療法セミナー
    • Related Report
      2018 Annual Research Report
  • [Presentation] ニボルマブ→イピリムマブ導入症例での重篤irAE2018

    • Author(s)
      木庭幸子
    • Organizer
      第2回甲信メラノーマカンファレンス
    • Related Report
      2018 Annual Research Report
  • [Presentation] Diversity of circulating tumor cells in peripheral blood: Detection of heterogeneous BRAF mutations in a patient with advanced melanoma by single-cell analysis.2017

    • Author(s)
      Kiniwa Y, Nakamura K, Mikoshiba A, Uchiyama A, Akiyama Y, Morimoto A, Okuyama R.
    • Organizer
      World Congress of Melanoma
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] 希少疾患用医薬品の採算性ある事業化と適応拡大戦略2018

    • Author(s)
      木庭幸子
    • Total Pages
      8
    • Publisher
      技術情報協会
    • Related Report
      2018 Annual Research Report
  • [Book] 次世代を担う、核酸医薬、免疫療法、遺伝子治療、細胞医薬品の課題と各疾患治療への横断的展開2017

    • Author(s)
      木庭幸子
    • Total Pages
      150
    • Publisher
      技術情報協会
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 2.抗癌剤投与効果予測方法2017

    • Inventor(s)
      奥山隆平,木庭幸子,秋山泰之,森本敦史,
    • Industrial Property Rights Holder
      奥山隆平,木庭幸子,秋山泰之,森本敦史,
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2023-01-30  

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