Analysis of minimal residual disease in ovarian cancer
Project/Area Number |
20K18174
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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Research Institution | Keio University |
Principal Investigator |
Masuda Kenta 慶應義塾大学, 医学部(信濃町), 助教 (30773460)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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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)
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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。
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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.
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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。
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Report
(4 results)
Research Products
(20 results)
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[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.
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Journal Title
J Gynecol Oncol.
Volume: 33
Issue: 5
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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[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
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[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
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