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

Search for biomarkers and novel therapeutic strategies targeting heterogeneity and plasticity in prostate cancer

Research Project

Project/Area Number 17K11158
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

KOSAKA Takeo  慶應義塾大学, 医学部(信濃町), 講師 (30445407)

Co-Investigator(Kenkyū-buntansha) 本郷 周  慶應義塾大学, 医学部(信濃町), 助教 (10626675)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords去勢抵抗性前立腺癌 / 血液循環腫瘍細胞 / cfDNA / リキッドバイオプシー / 次世代シーケンサー / 遺伝子パネル検査 / リプログラミング / 腫瘍内不均一性 / 前立腺癌 / シングルセル解析 / セルフリーDNA / 薬剤耐性
Outline of Final Research Achievements

Castration-resistant prostate cancer (CRPC) is heterogeneous and plastic.The establishment of new treatment strategies for refractory prostate cancer is an urgent task.Establishment of sample collection method for patient-specific molecular monitoring by liquid biopsy (blood circulation tumor cells, cfDNA),
Integrated analysis of liquid biopsy specimens and biopsy specimens by NGS analysis,We conducted a new drug screening using omics data of anti-cancer drug resistant human CRPC cell line. We succeeded in improving the recovery rate of CTC by label-free and single RNA sequence analysis, We identified its significance as a biomarker. NGS analysis was performed on biopsy samples taken at the same time as the cfDNA of patients with metastatic prostate cancer to identify common gene mutations.We have identified novel seeds that reprogram cabazitaxel resistance.

Academic Significance and Societal Importance of the Research Achievements

去勢抵抗性前立腺癌患者のおける患者個別化分子モニタリングのためのリキッドバイオプシー(血液循環腫瘍細胞、cfDNA)検体採取方法を確立した。リキッドバイオプシー検体と生検検体のNGS解析による統合的解析により、バイオマーカーとしての意義を見出すとともに、不均一性や検体採取の将来的な遺伝子解析のプラットフォームの実用性検証のための予備的データを得た。抗がん剤耐性ヒトCRPC細胞株のオミックスデータを応用した新規薬剤スクリーニングを実施した。カバジタキセル耐性をリプログラミングする新規シーズを同定した。難治性を克服し、患者の予後を改善する社会的意義を有する成果が得られた。

Report

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

    (28 results)

All 2020 2019 2018 2017 Other

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 6 results) Remarks (2 results)

  • [Journal Article] Aggressive prostate cancer with somatic loss of the homologous recombination repair gene FANCA: a case report2020

    • Author(s)
      Hongo Hiroshi、Kosaka Takeo、Aimono Eriko、Nishihara Hiroshi、Oya Mototsugu
    • Journal Title

      Diagnostic Pathology

      Volume: 15 Issue: 1 Pages: 916-919

    • DOI

      10.1186/s13000-019-0916-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sulfasalazine could modulate the CD 44v9‐xCT system and enhance cisplatin‐induced cytotoxic effects in metastatic bladder cancer2019

    • Author(s)
      Ogihara Koichiro、Kikuchi Eiji、Okazaki Shogo、Hagiwara Masayuki、Takeda Toshikazu、Matsumoto Kazuhiro、Kosaka Takeo、Mikami Shuji、Saya Hideyuki、Oya Mototsugu
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 4 Pages: 1431-1441

    • DOI

      10.1111/cas.13960

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Complete response with early introduction of cabazitaxel in a patient with multiple lung metastases of castration-resistant prostate cancer following the early detection of metastases using liquid biopsy: a case report2019

    • Author(s)
      Kosaka Takeo、Hongo Hiroshi、Oya Mototsugu
    • Journal Title

      BMC Cancer

      Volume: 19 Issue: 1 Pages: 5782-5784

    • DOI

      10.1186/s12885-019-5782-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Japanese Case of Enzalutamide-Resistant Prostate Cancer Harboring a SPOP Mutation With Scattered Allelic Imbalance: Response to Platinum-Based Therapy.2019

    • Author(s)
      Watanabe K, Kosaka T, Aimono E, Hongo H, Mikami S, Nishihara H, Oya M
    • Journal Title

      Clinical Genitourinary Cancer

      Volume: 17 Issue: 5 Pages: e897-e902

    • DOI

      10.1016/j.clgc.2019.06.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A first Japanese case of neuroendocrine prostate cancer accompanied by lung and brain metastasis with somatic and germline BRCA2 mutation2019

    • Author(s)
      Kosaka Takeo、Hongo Hiroshi、Aimono Eriko、Matsumoto Kazuhiro、Hayashida Tetsu、Mikami Shuji、Nishihara Hiroshi、Oya Mototsugu
    • Journal Title

      Pathology International

      Volume: 69 Issue: 12 Pages: 715-720

    • DOI

      10.1111/pin.12860

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-cell RNA-seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD632018

    • Author(s)
      Tanaka Nobuyuki、Katayama Shintaro、Reddy Aparna、Nishimura Kaneyasu、Niwa Naoya、Hongo Hiroshi、Ogihara Koichiro、Kosaka Takeo、Mizuno Ryuichi、Kikuchi Eiji、Mikami Shuji、Miyakawa Ayako、Arenas Ernest、Kere Juha、Oya Mototsugu、Uhl?n Per
    • Journal Title

      Cancer Medicine

      Volume: 7 Issue: 12 Pages: 6193-6204

    • DOI

      10.1002/cam4.1828

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prognostic significance of grade 3/4 neutropenia in Japanese prostate cancer patients treated with cabazitaxel.2018

    • Author(s)
      Kosaka T, Shinojima T, Morita S, Oya M.
    • Journal Title

      Cancer Sci.

      Volume: in press Issue: 5 Pages: 1570-1575

    • DOI

      10.1111/cas.13556

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PKM2 under hypoxic environment causes resistance to mTOR inhibitor in human castration resistant prostate cancer2018

    • Author(s)
      Yasumizu Yota、Hongo Hiroshi、Kosaka Takeo、Mikami Shuji、Nishimoto Koshiro、Kikuchi Eiji、Oya Mototsugu
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 45 Pages: 27698-27707

    • DOI

      10.18632/oncotarget.25498

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of cabazitaxel-resistant mechanism in human castration-resistant prostate cancer2018

    • Author(s)
      Hongo Hiroshi、Kosaka Takeo、Oya Mototsugu
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 9 Pages: 2937-2945

    • DOI

      10.1111/cas.13729

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] No significant impact of patient age and prior treatment profile with docetaxel on the efficacy of cabazitaxel in patient with castration-resistant prostate cancer2018

    • Author(s)
      Kosaka Takeo、Hongo Hiroshi、Watanabe Keitaro、Mizuno Ryuichi、Kikuchi Eiji、Oya Mototsugu
    • Journal Title

      Cancer Chemotherapy and Pharmacology

      Volume: 82 Issue: 6 Pages: 1061-1066

    • DOI

      10.1007/s00280-018-3698-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Vasohibin-1 as a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer2018

    • Author(s)
      Kobayashi Hiroaki, Kosaka Takeo, Mikami Shuji, Miyazaki Yasumasa, Matsumoto Kazuhiro, Kikuchi Eiji, Miyajima Akira, Kameyama Kaori, Sato Yasufumi, Oya Mototsugu
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 12 Pages: 10203-10210

    • DOI

      10.18632/oncotarget.23011

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reactive oxygen species induction by cabazitaxel through inhibiting Sestrin-3 in castration resistant prostate cancer.2017

    • Author(s)
      prostate cancer. Kosaka T, Hongo H, Miyazaki Y, Nishimoto K, Miyajima A, Oya M.
    • Journal Title

      Oncotarget.

      Volume: 8(50) Issue: 50 Pages: 87675-87683

    • DOI

      10.18632/oncotarget.21147

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] G2/M期制御因子を標的としたカバジタキセル耐性前立腺癌克服薬剤のIn silico screening2019

    • Author(s)
      本郷, 周 小坂, 威雄 楊井, 祥典 安水, 洋太 宮崎, 保匡 水野, 隆一 菊地, 栄次 大家, 基嗣
    • Organizer
      107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] タキサン系抗癌剤耐性前立腺癌に対するトポイソメラーゼ阻害剤の有用性2019

    • Author(s)
      本郷, 周 小坂, 威雄 安水, 洋太 宮崎, 保匡 田中, 伸之 武田, 利和 松本, 一宏 森田, 伸也 水野, 隆一 大家, 基嗣
    • Organizer
      57回日本癌治療学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 前立腺癌薬物治療のパラダイムシフト バイオマーカーのパラダイムシフト Precision medicineに向けて2019

    • Author(s)
      小坂, 威雄 大家, 基嗣
    • Organizer
      107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Innovative approach for cancer by advanced microscopy Visualizing Intratumoral Heterogeneity by 3D Light Sheet Microscopy: Cell-by-Cell Protein/RNA Analysis in Intact Tumors2019

    • Author(s)
      田中, 伸之 三上, 修治 小坂, 威雄 水野, 隆一 大家, 基嗣
    • Organizer
      78回日本癌学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ゲムシタビン耐性膀胱癌は癌蛋白MUC1Cを介して、シスプラチンへの交叉耐性を獲得する2019

    • Author(s)
      茂田, 啓介 菊地, 栄次 長谷川, 政徳 荻原, 広一郎 小坂, 威雄 水野, 隆一 宮嶋, 哲 大家, 基嗣
    • Organizer
      107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Network Medicine to Overcome Drug Resistance in CRPC or NEPC: Drug Efficacy Reprogramming2018

    • Author(s)
      小坂威雄
    • Organizer
      第106回日本泌尿器科学会総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 前立腺癌のリキッドバイオプシー(血液循環腫瘍細胞:CTC)の現状と課題2018

    • Author(s)
      小坂威雄、本郷周、大家基嗣
    • Organizer
      第56回日本癌治療学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] CRPC に対する抗がん化学療法の現況と課題:リアルワールドデータから考察する2018

    • Author(s)
      小坂威雄
    • Organizer
      日本泌尿器腫瘍学会第4回学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Roles of topoisomerase inhibitors and cisplatin for CRPC in the post-cabazitaxel setting2018

    • Author(s)
      Kosaka T, Hongo H, Yasumizu Y, Miyazaki Y, Kikuchi E, Oya M
    • Organizer
      AUA Annual Meeting San Francisco: 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] In silico screening using RNA-seq data sets of Neuroendocrine prostate cancer has identified candidate drugs for reprogramming NEPC-specific signatures2018

    • Author(s)
      Kosaka T, Hongo H, Mikami S, Matsumoto K, Kikuchi E, Oya M:
    • Organizer
      AUA Annual Meeting San Francisco: 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 前立腺癌におけるLiquid Biopsyの現状と課題2017

    • Author(s)
      小坂威雄、大家基嗣
    • Organizer
      第82回日本泌尿器科学会東部総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 有効性と安全性の狭間から見えてきたカバジタキセル使用の実際2017

    • Author(s)
      小坂威雄、篠島利明、森田伸也、大家基嗣
    • Organizer
      第82回日本泌尿器科学会東部総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] BCL6を標的としたエンザルタミド耐性去勢抵抗性前立腺癌克服戦略2017

    • Author(s)
      本郷周、小坂威雄、宮崎保匡、菊地栄次、大家基嗣
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 上皮間葉移行に着目したカバジタキセル耐性去勢抵抗性前立腺癌克服戦略2017

    • Author(s)
      本郷周、小坂威雄、菊地栄次、宮嶋哲、大家基嗣
    • Organizer
      第21回日本がん分子標的治療学会学術集会
    • Related Report
      2017 Research-status Report
  • [Remarks] 慶應義塾大学医学部泌尿器科学教室ホームページ

    • URL

      http://www.keio-urology.jp/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 慶應義塾大学医学部泌尿器科学教室

    • URL

      http://www.keio-urology.jp/

    • Related Report
      2018 Research-status Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi