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Individualized molecular targeted therapy for high-grade ovarian serous carcinoma

Research Project

Project/Area Number 22K09630
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionKindai University

Principal Investigator

Nakai Hidekatsu  近畿大学, 医学部, 准教授 (20441082)

Co-Investigator(Kenkyū-buntansha) 松村 謙臣  近畿大学, 医学部, 教授 (20452336)
濱西 潤三  京都大学, 医学研究科, 准教授 (80378736)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords卵巣高異型度漿液性癌 / 血管新生阻害薬 / 感受性予測因子 / 組織サブタイプ分類 / 化学療法感受性予測 / 高異型度漿液性癌 / 化学療法の奏功規定因子 / 卵巣癌
Outline of Research at the Start

現在、卵巣高異型度漿液性癌(HGSOC)の分子標的治療薬は、血管新生阻害薬、PARP阻害薬と免疫チェックポイント阻害薬を用いた治療を柱に臨床試験が行われている。これらの分子標的治療薬による個別化治療のため、どのような症例にどの分子標的治療薬を用いるべきかを明らかにするためにバイオマーカー探索を行う。

Outline of Final Research Achievements

We investigated the prediction of the efficacy of angiogenesis inhibitors. Histologic subtype classification using artificial intelligence was reproducible, and histologic subtype classification can be used as a predictor of sensitivity to bevacizumab. We investigated the prediction of sensitivity to PARP inhibitors using gene panel testing and immunohistochemical staining of SLFN11, DSS1, BRCA1, and RAD51. None of the biomarkers was a predictor of sensitivity to PARP inhibitors for long-term response. We also investigated the prediction of sensitivity to immune checkpoint inhibitors. We reported that α-IL-6 suppresses tumor immunity and IL-17 increases the number of T cells.

Academic Significance and Societal Importance of the Research Achievements

卵巣高異型度漿液性癌を、HE標本のバーチャルスライドを用いて4つの形態学的サブタイプ分類を行って、血管新生や免疫反応についての関連性を検討し、血管新生阻害薬であるベバシズマブの感受性予測が可能であったと報告した。
本研究では4つの形態学的サブタイプ分類の詳細な分類手順を紹介し、web上で公開されたスライドを用いてトレーニングすることが可能であり広く臨床普及が期待できる。また人工知能を用いたアルゴリズムも公開しており、これを用いることで本研究に参加してない研究者にもベバシズマブの感受性予測が可能となり臨床普及が期待される。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (37 results)

All 2024 2023 2022 2021

All Journal Article (24 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 24 results,  Open Access: 8 results) Presentation (13 results)

  • [Journal Article] Artificial Intelligence-Based Histopathological Subtyping of High-Grade Serous Ovarian Cancer.2024

    • Author(s)
      Ueda A, Nakai H, Miyagawa C, Otani T, Yoshida M, Murakami R, Komiyama S, Tanigawa T, Yokoi T, Takano H, Baba T, Miura K, Shimada M, Kigawa J, Enomoto T, Hamanishi J, Okamoto A, Okuno Y, Mandai M, Matsumura N.
    • Journal Title

      Am J Pathol.

      Volume: 194 Pages: 1913-1923

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study.2024

    • Author(s)
      Aoki D, Tabata T, Yanagida S, Nakamura T, Kondo E, Hamanishi J, Harano K, Hasegawa K, Hirasawa T, Hori K, Komiyama S, Matsuura M, Nakai H, Nakamura H, Sakata J, Takehara K, Takekuma M, Yokoyama Y, Kase Y, Sumino S, Soeda J, Kato A, Suri A, Okamoto A, Sugiyama T.
    • Journal Title

      J Gynecol Oncol.

      Volume: 35 Pages: 114-114

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer: final results of a multicenter phase 2 study.2024

    • Author(s)
      Itamochi H, Takeshima N, Hamanishi J, Hasegawa K, Matsuura M, Miura K, Nagao S, Nakai H, Tanaka N, Tokunaga H, Nishio S, Watari H, Yokoyama Y, Kase Y, Sumino S, Kato A, Suri A, Yasuoka T, Takehara K.
    • Journal Title

      J Gynecol Oncol.

      Volume: 35 Pages: 115-115

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Trends in gynecologic cancer in Japan: incidence from 1980 to 2019 and mortality from 1981 to 2021.2024

    • Author(s)
      Nakai H, Higashi T, Kakuwa T, Matsumura N.
    • Journal Title

      Int J Clin Oncol.

      Volume: 29 Pages: 363-371

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pretreatment systemic inflammatory markers predict survival in endometrial cancer: A Japanese Gynecologic Oncology Group 2043 exploratory data analysis.2024

    • Author(s)
      Nishio S, Murotani K, Yamagami W, Suzuki S, Nakai H, Kato K, Tokunaga H, Nomura H, Yokoyama Y, Takehara K, Okamoto A.
    • Journal Title

      Gynecol Oncol.

      Volume: 181 Pages: 46-53

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Declining Prevalence of Human Papillomavirus Co-Infections Among Young Japanese Women With Cervical Cancer and Its Precursors.2024

    • Author(s)
      Yoshiizumi E, Onuki M, Kukimoto I, Takahashi F, Matsui T, Hamasaki K, Kanao H, Nio A, Yahata H, Goda M, Yokoyama T, Hisa T, Tasaki K, Tenjimbayashi Y, Saji H, Kudaka W, Takei Y, Shigeta S, Motohara T, Matsumiya H, Nakamura K, Yoshida H, Ishikawa M, Hamanishi J, Nakai H, et al.
    • Journal Title

      J Med Virol.

      Volume: 96 Pages: 70096-70096

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Veliparib with frontline chemotherapy and as maintenance in Japanese women with ovarian cancer: a subanalysis of efficacy, safety, and antiemetic use in the phase 3 VELIA trial.2023

    • Author(s)
      Mizuno M, Ito K, Nakai H, Kato H, Kamiura S, Ushijima K, Nagao S, Takano H, Okadome M, Takekuma M, Tokunaga H, Nagase S, Aoki D, Coleman RL, Nishimura Y, Ratajczak CK, Hashiba H, Xiong H, Katsumata N, Enomoto T, Okamoto A.
    • Journal Title

      Int J Clin Oncol.

      Volume: 28 Pages: 163-174

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Histopathological subtyping of high-grade serous ovarian cancer using whole slide imaging.2023

    • Author(s)
      Miyagawa C, Nakai H, Otani T, Murakami R, Takamura S, Takaya H, Murakami K, Mandai M, Matsumura N.
    • Journal Title

      J Gynecol Oncol.

      Volume: 34 Issue: 4

    • DOI

      10.3802/jgo.2023.34.e47

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment for Locally Resectable Stage IIIC1 Cervical Cancer: A Retrospective, Single-Institution Study.2023

    • Author(s)
      Kashima Y, Murakami K, Miyagawa C, Takaya H, Kotani Y, Nakai H, Matsumura N.
    • Journal Title

      Healthcare

      Volume: 11 Pages: 632-632

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Progression after discontinuation of bevacizumab in the first-line treatment of ovarian cancer2023

    • Author(s)
      Nakai Hidekatsu、Matsumura Noriomi
    • Journal Title

      Annals of Translational Medicine

      Volume: 11 Issue: 5 Pages: 229-229

    • DOI

      10.21037/atm-22-6389

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comment on 'Population-adjusted indirect treatment comparison of maintenance PARP inhibitor with or without bevacizumab versus bevacizumab alone in women with newly diagnosed advanced ovarian cancer'.2023

    • Author(s)
      Nakai H, Matsumura N.
    • Journal Title

      Ther Adv Med Oncol.

      Volume: 15

    • DOI

      10.1177/17588359231168509

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of an Algorithm to Differentiate Uterine Sarcoma from Fibroids Using MRI and LDH Levels.2023

    • Author(s)
      Suzuki A, Kido A, Matsuki M, Kotani Y, Murakami K, Yamanishi Y, Numoto I, Nakai H, Otani T, Konishi I, Mandai M, Matsumura N.
    • Journal Title

      Diagnostics

      Volume: 13 Issue: 8 Pages: 1404-1404

    • DOI

      10.3390/diagnostics13081404

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diagnostic Utility of Hysteroscopic Biopsy in Cases of Suspected Lobular Endocervical Glandular Hyperplasia and Comparison with Cervical Conization.2023

    • Author(s)
      Shiro R, Kotani Y, Ohta M, Sato H, Kashima Y, Murakami K, Kawasaki K, Nakai H, Matsumura N.
    • Journal Title

      Healthcare

      Volume: 11 Issue: 11 Pages: 1619-1619

    • DOI

      10.3390/healthcare11111619

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Time-Dependent Changes in Risk of Progression During Use of Bevacizumab for Ovarian Cancer2023

    • Author(s)
      Takamatsu Shiro、Nakai Hidekatsu、Yamaguchi Ken、Hamanishi Junzo、Mandai Masaki、Matsumura Noriomi
    • Journal Title

      JAMA Network Open

      Volume: 6 Issue: 8 Pages: 2326834-2326834

    • DOI

      10.1001/jamanetworkopen.2023.26834

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Selection of maintenance therapy during first-line treatment of advanced ovarian cancer based on pharmacologic characteristics.2023

    • Author(s)
      Nakai H, Matsumura N.
    • Journal Title

      Expert Opin Pharmacother.

      Volume: 24 Issue: 18 Pages: 2161-2173

    • DOI

      10.1080/14656566.2023.2295393

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ovarian teratoid carcinosarcoma with a PIK3CA mutation: a case report and review of the literature.2022

    • Author(s)
      Masato Aoki, Hisamitsu Takaya, Tomoyuki Otani, Hidekatsu Nakai, Kosuke Murakami, Noriomi Matsumura.
    • Journal Title

      Int Cancer Conf J.

      Volume: 11 Issue: 4 Pages: 231-237

    • DOI

      10.1007/s13691-022-00571-w

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Outcomes of Pregnancies and Deliveries of Patients Who Underwent Fertility-Preserving Surgery for Early-Stage Epithelial Ovarian Cancer.2022

    • Author(s)
      Shin Nishio, Takayo Takeno, Takashi Fukuda, Aymi Shikama, Hidekastu Nakai, Hiroko Nakamura, Hideyuki Tokunaga, Kazuaki Takahashi, Emi Okuma, Masahiko Mori, Yasuhisa Terao, Kimio Ushijima, Nobuo Yaegashi.
    • Journal Title

      . J Clin Med.

      Volume: 11 Issue: 18 Pages: 5346-5346

    • DOI

      10.3390/jcm11185346

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regional differences in human papillomavirus type 52 prevalence among Japanese women with cervical intraepithelial neoplasia2022

    • Author(s)
      Kukimoto Iwao、Onuki Mamiko、Yaegashi Nobuo、Matsumoto Koji、MINT Study Group
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 52 Pages: 1428-1434

    • DOI

      10.1093/jjco/hyac127

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] CXCL13-producing CD4+ T cells accumulate in the early phase of tertiary lymphoid structures in ovarian cancer2022

    • Author(s)
      Ukita Masayo、Hamanishi Junzo、Yoshitomi Hiroyuki、Yamanoi Koji、Takamatsu Shiro、Ueda Akihiko、Suzuki Haruka、Hosoe Yuko、Furutake Yoko、Taki Mana、Abiko Kaoru、Yamaguchi Ken、Nakai Hidekatsu、Baba Tsukasa、Matsumura Noriomi、Yoshizawa Akihiko、Ueno Hideki、Mandai Masaki
    • Journal Title

      JCI Insight

      Volume: 7 Issue: 12 Pages: 157215-157215

    • DOI

      10.1172/jci.insight.157215

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The roles and limitations of bevacizumab in the treatment of ovarian cancer.2022

    • Author(s)
      Hidekatsu Nakai, Noriomi Matsumura.
    • Journal Title

      Int J Clin Oncol.

      Volume: 27 Issue: 7 Pages: 1120-1126

    • DOI

      10.1007/s10147-022-02169-x

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Individualization in the first-line treatment of advanced ovarian cancer based on the mechanism of action of molecularly targeted drugs.2022

    • Author(s)
      Hidekatsu Nakai, Noriomi Matsuymura.
    • Journal Title

      Int J Clin Oncol.

      Volume: 27 Issue: 6 Pages: 1001-1012

    • DOI

      10.1007/s10147-022-02163-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan2022

    • Author(s)
      Tanaka Tomohito、Matsumura Noriomi、et al.
    • Journal Title

      International Journal of Clinical Oncology

      Volume: - Issue: 6 Pages: 1084-1092

    • DOI

      10.1007/s10147-022-02152-6

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changes in HPV16/18 Prevalence among Unvaccinated Women with Cervical Intraepithelial Neoplasia in Japan: Assessment of Herd Effects following the HPV Vaccination Program.2022

    • Author(s)
      Onuki M, Matsumoto K, et al. for The Mint Study Group.
    • Journal Title

      Vaccines (Basel)

      Volume: 10 Issue: 2 Pages: 181-181

    • DOI

      10.3390/vaccines10020188

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The efficacy of human papillomavirus vaccination in young Japanese girls: the interim results of the OCEAN study2021

    • Author(s)
      Hiramatsu Kosuke、Matsumura Noriomi, et al.
    • Journal Title

      Human Vaccines and Immunotherapeutics

      Volume: 18 Issue: 1 Pages: 1951098-1951098

    • DOI

      10.1080/21645515.2021.1951098

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 白金感受性再発卵巣癌維持療法におけるオラパリブ効果予測因子の解析 KCOG-G2101s2024

    • Author(s)
      福田 奈穂, 高島 剛志, 森井 英一, 中井 英勝, 吉岡 恵美, 伊藤 公彦, 磯野 路善, 鍔本 浩志, 勝田 隆博, 長野 浩明, 甲斐 健太郎, 藤原 聡枝, 本橋 卓, 荒川 敦志, 坂井 和子, 松村 謙臣
    • Organizer
      第66回日本婦人科腫瘍学会学術講演会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 婦人科悪性腫瘍におけるMSI-high腫瘍についての多施設共同研究2024

    • Author(s)
      加嶋 洋子, 松村 謙臣, 中井 英勝, 甲斐 健太郎, 金田 倫子, 勝田 隆博, 望月 亜矢子, 寄木 香織, 藤原 聡枝, 吉岡 恵美, 竹中 基記, 伊藤 公彦
    • Organizer
      第76回日本産科婦人科学会学術講演会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 婦人科悪性腫瘍529例から抽出されたMSI-H腫瘍56例の検討(Fifty-six cases of MSI-high gynecological tumors identified from 529 cases))2024

    • Author(s)
      大谷 知之, 加嶋 洋子, 中井 英勝, 吉岡 恵美, 望月 亜矢子, 藤原 聡枝, 寄木 香織, 竹中 基記, 勝田 隆博, 松村 謙臣
    • Organizer
      第113回日本病理学会学術講演会
    • Related Report
      2024 Annual Research Report
  • [Presentation] IL17が卵巣明細胞がんの腫瘍微小環境に及ぼす影響と免疫療法への展開2024

    • Author(s)
      村上 幸祐, 宮川 知保, 高村 史記, 垣見 和宏, 加嶋 洋子, 長岡 孝治, 小林 由香利, 松村 謙臣
    • Organizer
      第66回日本婦人科腫瘍学会学術講演会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Lynch症候群において組織型および遺伝子特性の異なる子宮・卵巣の重複癌を認めた一例2023

    • Author(s)
      太田 真見子, 宮川 知保, 中井 英勝, 松村 謙臣
    • Organizer
      第61回日本癌治療学会
    • Related Report
      2023 Research-status Report
  • [Presentation] 当院の再発子宮内膜癌に対するPembrolizumab+Lenvatinib治療2023

    • Author(s)
      佐藤 華子, 加嶋 洋子, 太田 真見子, 宮川 知保, 小谷 泰史, 中井 英勝, 松村 謙臣
    • Organizer
      近畿産婦人科学会
    • Related Report
      2023 Research-status Report
  • [Presentation] 卵巣癌に対するオラパリブ使用の人参養栄湯の効果についての前向き観察研究 KCOG-G1904 study2023

    • Author(s)
      西江 瑠璃, 藤原 聡枝, 伊東 史学, 谷口 真紀子, 青木 稚人, 中井 英勝, 松村 謙臣, 田崎 和人, 西尾 真, 吉岡 恵美, 堀 謙輔, 荒川 敦志, 小池 大我, 坊本 佳優, 早崎 容, 本橋 卓, 伊藤 公彦
    • Organizer
      第65回日本婦人科腫瘍学会
    • Related Report
      2023 Research-status Report
  • [Presentation] 婦人科悪性腫瘍におけるMSI-high腫瘍についての多施設共同研究2023

    • Author(s)
      加嶋 洋子, 中井 英勝, 松村 謙臣, 吉岡 恵美, 森 泰輔, 金田 倫子, 甲斐 健太郎, 勝田 隆博, 竹中 基記, 荒川 敦志, 伊藤 公彦, 平嶋 泰之, 寄木 香織, 藤原 聡枝, 望月 亜矢子
    • Organizer
      第65回日本婦人科腫瘍学会
    • Related Report
      2023 Research-status Report
  • [Presentation] 治癒を目指した初回進行卵巣癌の維持療法2023

    • Author(s)
      中井 英勝
    • Organizer
      近畿産婦人科学会
    • Related Report
      2023 Research-status Report
  • [Presentation] 進行卵巣癌初回治療時のPARP阻害剤維持療法の投与状況を調べるための多機関共同研究2023

    • Author(s)
      加嶋 洋子, 松村 謙臣, 中井 英勝, 小谷 泰史, 横井 猛, 金村 昌徳, 赤田 忍, 坂元 優太, 太田 行信, 深山 雅人
    • Organizer
      日本産科婦人科学会
    • Related Report
      2023 Research-status Report
  • [Presentation] 多施設共同研究におけるプラチナ感受性再発卵巣癌に対するオラパリブの奏効期間についての後方視的検討2022

    • Author(s)
      1 多施設共同研究におけるプラチナ感受性再発卵巣癌に対するオラパリ笹井 奈穂, 中井 英勝, 松村 謙臣, 藤原 聡枝, 磯野 路善, 吉岡 恵美, 西川 隆太郎, 本橋 卓, 荒川 敦志
    • Organizer
      第74回 日本産科婦人科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 卵巣高異型度漿液性癌の形態学的サブタイプ判定のためのトレーニングスライドの有用性2022

    • Author(s)
      宮川 知保, 中井 英勝, 高矢 寿光, 松村 謙臣
    • Organizer
      第64回 日本婦人科腫瘍学会
    • Related Report
      2022 Research-status Report
  • [Presentation] PARP阻害薬の変遷 卵巣高異型度漿液性がんにおけるHRD statusのintratumor heterogeneity2022

    • Author(s)
      中井 英勝, 高矢 寿光, 松村 謙臣
    • Organizer
      第64回 日本婦人科腫瘍学会
    • Related Report
      2022 Research-status Report

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Published: 2022-04-19   Modified: 2026-01-16  

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