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Analysis of minimal residual disease in ovarian cancer

Research Project

Project/Area Number 20K18174
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionKeio University

Principal Investigator

Masuda Kenta  慶應義塾大学, 医学部(信濃町), 助教 (30773460)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords卵巣癌 / 治療抵抗性 / 動物モデル / 微小残存病変 / マウスモデル / オルガノイド / RNA sequence
Outline of Research at the Start

卵巣癌、特に漿液性癌は、化学療法に対する寛解率が高いものの、その後高確率で再発に至る。その事実は、化学療法後に微小残存病変が存在し、卵巣癌再発の直接的な要因となっていることを示唆している。しかしながら卵巣癌微小残存病変に対する解析方法は確立されておらず、有効な治療法はない。
本研究では、卵巣癌再発の直接的原因である微小残存病変を治療標的とした”真の精密医療”を実現するため、化学療法前後の臨床検体を用いた網羅的遺伝子発現解析を行い、さらに卵巣癌の微小残存病変を模倣したin vitroモデルを開発を試み、新たな治療戦略を立案するための基礎データを得る。

Outline of Final Research Achievements

In order to develop therapies that inhibit recurrence of ovarian cancer, it is necessary to elucidate the mechanism by which minimal residual disease after chemotherapy is resistant to treatment. With this research project, we developed a new ovarian cancer mouse model based on the organoid culture method, created an in vitro model of minimal residual disease, performed the spatial gene expression analysis using human ovarian cancer samples, and succeeded in identifying characteristic gene expression patterns in ovarian cancer minimal residual disease. By integrating these data, we obtained results that lead to the proposal of a new treatment strategy. Using the developed model animals, we will proceed with research and development toward the POC acquisition and the development of new therapeutic strategies.

Academic Significance and Societal Importance of the Research Achievements

本研究課題で開発した卵巣癌モデルマウスは、BRCA1/2遺伝子野生型の特徴を持ち、卵巣癌の中でも予後不良群を模倣している。BRCA1/2遺伝子野生型の特徴を有する卵巣癌は、既存の細胞障害性薬剤や分子標的薬への感受性が低く、アンメットメディカルニーズが高い。そのため今後非臨床試験を計画する上でも有用な動物モデルとなり得る。またオルガノイド培養法を応用して作成した微小残存病変モデルは、in vitroスクリーニングによる治療候補薬剤の同定が期待できる。またヒト卵巣癌検体に対して、空間的遺伝子発現解析の有用性を示したことにより、今後普遍的な卵巣癌MRDシグネチャの同定が期待できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (20 results)

All 2022 2021 Other

All Int'l Joint Research (3 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (10 results) Book (1 results)

  • [Int'l Joint Research] オックスフォード大学(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] オックスフォード大学(英国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] オックスフォード大学(英国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Presence of spontaneous epithelial-mesenchymal plasticity in esophageal cancer2022

    • Author(s)
      Tsuchihashi Kenji、Hirata Yuki、Yamasaki Juntaro、Suina Kentaro、Tanoue Kenro、Yae Toshifumi、Masuda Kenta、Baba Eishi、Akashi Koichi、Kitagawa Yuko、Saya Hideyuki、Nagano Osamu
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 30 Pages: 101246-101246

    • DOI

      10.1016/j.bbrep.2022.101246

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SIK2 inhibition enhances PARP inhibitor activity synergistically in ovarian and triple-negative breast cancers2022

    • Author(s)
      Lu Z、Mao W、Yang H、Santiago-O’Farrill JM.、Rask PJ.、Mondal J、Chen H、Ivan C、Liu X、Liu CG、Xi Y、Masuda K、Carrami EM.、Chen M、Tang Y、Pang L、Lakomy DS、Calin GA、Liang H、Ahmed AA、Vankayalapati H、Bast RC
    • Journal Title

      Journal of Clinical Investigation

      Volume: 132 Issue: 11

    • DOI

      10.1172/jci146471

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] <i>TP53</i> variants in p53 signatures and the clonality of STICs in RRSO samples2022

    • Author(s)
      Akahane Tomoko、Masuda Kenta、Hirasawa Akira、Kobayashi Yusuke、Ueki Arisa、Kawaida Miho、Misu Kumiko、Nakamura Kohei、Nagai Shimpei、Chiyoda Tatsuyuki、Yamagami Wataru、Hayashi Shigenori、Kataoka Fumio、Banno Kouji、Sugano Kokichi、Okita Hajime、Kosaki Kenjiro、Nishihara Hiroshi、Aoki Daisuke
    • Journal Title

      Journal of Gynecologic Oncology

      Volume: 33 Issue: 4

    • DOI

      10.3802/jgo.2022.33.e50

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current status of hereditary breast and ovarian cancer practice among gynecologic oncologists in Japan: a nationwide survey by the Japan Society of Gynecologic Oncology (JSGO)2022

    • Author(s)
      Kobayashi Y, Masuda K, Hiraswa A, Takehara K, Tsuda H, Watanabe Y, Oda K, Nagase S, Mandai M, Okamoto A, Yaegashi N, Mikami M, Enomoto T, Aoki D, Katabuchi H; Working Group on Clinical Practice for Cancer Genomic Medicine and HBOC, Japan Society of Gynecologic Oncology.
    • Journal Title

      J Gynecol Oncol.

      Volume: 33 Issue: 5

    • DOI

      10.3802/jgo.2022.33.e61

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MEK inhibition suppresses metastatic progression of <i>KRAS</i> ‐mutated gastric cancer2022

    • Author(s)
      Yamasaki Juntaro、Hirata Yuki、Otsuki Yuji、Suina Kentaro、Saito Yoshiyuki、Masuda Kenta、Okazaki Shogo、Ishimoto Takatsugu、Saya Hideyuki、Nagano Osamu
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 3 Pages: 916-925

    • DOI

      10.1111/cas.15244

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells2021

    • Author(s)
      Artibani M, Masuda K, Hu Z, Rauher PC, Mallett G, Wietek N, Morotti M, Chong K, KaramiNejadRanjbar M, Zois CE, Dhar S, El-Sahhar S, Campo L, Blagden SP, Damato S, Pathiraja PN, Nicum S, Gleeson F, Laios A, Alsaadi A, Santana Gonzalez L, Motohara T, et al.
    • Journal Title

      JCI Insight.

      Volume: 6

    • DOI

      10.1172/jci.insight.147929

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] p53 dysfunction hampers the differentiation and causes the precancerous potency in mouse fallopian tube organoids2022

    • Author(s)
      Shimpei Nagai, Kenta Masuda,Tomohiro Tamura,Tomoko Akahane,Tatsuyuki Chiyoda,Yusuke Kobayashi,Kouji Banno,Mamoru Tanaka,Daisuke Aoki
    • Organizer
      第74回 日本産科婦人科学会学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] RNA sequencing analysis of ovarian cancer minimal residual disease revealed a metabolic signature that would lead to the development of a new therapeutic strategy2022

    • Author(s)
      Kenta Masuda,Ahmed Ashour Ahmed,Tomohiro Tamura,Shimpei Nagai,Yuya Nogami,Kosuke Tsuji,Yusuke Kobayashi,Kouji Banno,Mamoru Tanaka,Daisuke Aoki
    • Organizer
      第74回 日本産科婦人科学会学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Development of a new ovarian cancer mouse model by engineering mouse fallopian tube epithelial organoids2022

    • Author(s)
      Shimpei Nagai, Kenta Masuda,Tomohiro Tamura,Keiyo Imaeda,Eiji Sugihara,Juntaro Yamasaki,Yuji Otsuki,Hiroyuki Nobusue,Tatsuyuki Chiyoda,Yusuke Kobayashi,Kouji Banno,Daisuke Aoki,Hideyuki Saya,Osamu Nagano
    • Organizer
      第81回 日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] MEK inhibition suppresses metastatic progression of KRAS-mutated gastric cancer2022

    • Author(s)
      Juntaro Yamasaki,Yuji Otsuki,Kenta Masuda,Hideyuki Saya,Osamu Nagano
    • Organizer
      第81回 日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 予後不良卵巣癌の克服を目指した卵巣癌モデルマウスの開発2022

    • Author(s)
      増田健太,永井晋平,田村友宏,今枝慶蓉,千代田達幸,小林佑介,阪埜浩司,佐谷秀行,永野修,青木大輔
    • Organizer
      第21回 日本婦人科がん分子標的研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 卵巣漿液性癌細胞株において脂肪酸酸化阻害はオラパリブに対する感受性を増加させる2021

    • Author(s)
      増田 健太、Ahmed Ahmed、永井 晋平、小林 佑介、冨永 英一郎、阪埜 浩司、田中 守、青木 大輔
    • Organizer
      第73回日本産科婦人科学会
    • Related Report
      2021 Research-status Report
  • [Presentation] RRSO検体におけるp53 signatureとSTICの特性に関する検討2021

    • Author(s)
      赤羽 智子、増田 健太、平沢 晃、小林 佑介、永井 晋平、千代田 達幸、林 茂徳、片岡 史夫、冨永 英一郎、阪埜 浩司、田中 守、青木 大輔
    • Organizer
      第73回日本産科婦人科学会
    • Related Report
      2021 Research-status Report
  • [Presentation] p53 dysfunction hampers the differentiation of mouse fallopian tube organoids2021

    • Author(s)
      Nagai S,Masuda K,Tamura T,Otsuki Y,Suina K,Nobusue H,Akahane T,Chiyoda T,Kobayashi Y,Banno K,Aoki D,Saya H,Nagano O
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Investigating minimal residual disease and chemotherapy resistance in ovarian cancer2021

    • Author(s)
      Masuda K,Artibani M,Nagai S,Kobayashi Y,Banno K,Saya H,Aoki D,Ahmed AA
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Analysis using a mouse ovarian cancer organoid model reveals cancer heterogeneity and cancer stem-like cell properties2021

    • Author(s)
      Tamura T,Masuda K,Nagai S,Otsuki Y,Suina K,Nobusue H,Sampetrean O,Banno K,Aoki D,Saya H,Nagano O
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Book] Hereditary Ovarian Cancer / Hereditary Breast and Ovarian Cancer:Molecular Mechanism and Clinical Practice2021

    • Author(s)
      Masuda K,Satake M,Aoki D
    • Total Pages
      332
    • Publisher
      Springer
    • ISBN
      9789811645211
    • Related Report
      2021 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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