Molecular mechanism of progression to castration resistant prostate cancer and its application for tailor made treatment

• Project/Area Number: 25462503
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Toho University
• Principal Investigator: SUZUKI Hiroyoshi 東邦大学, 医学部, 教授 (60301818)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 前立腺癌 / 去勢抵抗性前立腺癌 / ERG / 予後予測モデル / PET / ドセタキセル / 酢酸アビラテロン / アンチアンドロゲン / アンドロゲン受容体 / 予測モデル / アビラテロン / PTEN / ホルモン療法

Outline of Final Research Achievements

To investigate the association of ERG expression, one of the most important molecular mechanism of progression to castration resistant prostate cancer (CRPC), with other molecular abnormalities, we examined specimens from radical prostatectomy, prostate biopsy, trans-urethral resection and autopsy. We examined the potential association of ERG expression and other gene abnormalities and clinical factors and found that ERG expression plays an important role of progression of CRPC. Especially, ERG expression was strongly related to PTEN expression.
Also, we examined prognostic factors for efficacy of each CRPC drugs and made statistical prognostic models (nomograms).
We have developed novel PET diagnostic drug reconizing amino acid tranportor and we attended the first global advanced prostate cancer conference held at St. Gallen, Switzland as a consensus panel member and debated about these new findings and other future CRPC treatment.

Research Products

• [Int'l Joint Research] University of Tampere(フィンランド)
• [Int'l Joint Research] Johns Hopkins University(米国)
• [Journal Article] Effect of androgen deprivation therapy on arterial stiffness and serum lipid profile changes in patients with prostate cancer: a prospective study of initial 6-month follow-up. (2016)
  • Author(s): Oka R, Utsumi T, Yano M, Kamijima S, Kamiya N, Shirai K, Suzuki H
  • Journal Title: Int J Clin Oncol Volume: 21 Issue: 2 Pages: 389-396
  • DOI: 10.1007/s10147-015-0891-7
  • Peer Reviewed
• [Journal Article] Validation of active surveillance criteria for pathologically insignificant prostate cancer in Asian men (2016)
  • Author(s): Yamada Y, Sakamoto S, Sazuka T, Goto Y, Kawamura K, Imamoto T, Nihei N, Suzuki H, Akakura K, Ichikawa T.
  • Journal Title: Journal of Urology Volume: 23 Issue: 1 Pages: 49
  • DOI: 10.1111/iju.12952
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Diagnostic performance and safety of NMK36 (trans-1-Amino-3-[18F] fluorocyclobutanecarboxylic acid)-PET/CT in primary prostate cancer: Multicenter phase IIb clinical trial. (2016)
  • Author(s): Suzuki H, Inoue Y, Fujimoto H, Yonase J, Tanabe K, Fukasawa S, Inoue T, Saito S, Ueno M, Otaka A, Murakami K, Ishihara K, Kaji Y, Kuroki Y, Koizumi K, Yoshimura M, Takahashi H
  • Journal Title: Jpn J Clin Oncol Volume: 46 Issue: 2 Pages: 152-162
  • DOI: 10.1093/jjco/hyv181
  • Peer Reviewed / Open Access
• [Journal Article] A multi-center retrospective analysis of sequential treatment of abiraterone acetate followed by docetaxel in Japanese patients with metastatic castration-resistant prostate cancer. (2015)
  • Author(s): Ueda Y, Matsubara N, Takizawa I, Nishiyama T, Yabata K, Satoh T, Kamiya N, Suzuki H, Kawahara T, Uemura H
  • Journal Title: Jpn J Clin Oncol Volume: 45 Issue: 8 Pages: 774-779
  • DOI: 10.1093/jjco/hyv070
  • Peer Reviewed / Open Access
• [Journal Article] Management of patients with advanced prostate cancer: Recommendations of the St.Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015. (2015)
  • Author(s): Gillessen S, Omlin A, Attard G, de Bono JS, Nelson PS, Sartor O, Smith MR, Soule HR, Akaza H, Beer TM, Beltran H, Chinnaiyan AM, Daugaard G, Davis ID, De Santis M, Olmos D, Padhani AR, Parker C, Rubin MA, Schalken JA, Scher HI, Sella A, Shore ND, Small EJ, Sternberg CN, Suzuki H, Sweeney CJ, Tannock IF, Tombal B
  • Journal Title: Ann Oncol Volume: 26 Issue: 8 Pages: 1589-1604
  • DOI: 10.1093/annonc/mdv257
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] External validation and comparison of two nomograms predicting the probability of Gleason sum upgrading between biopsy and radical prostatectomy pathology in two patient populations: a retrospective cohort study. (2015)
  • Author(s): Utsumi T, Oka R, Endo T, Yano M, Kamijima S, Kamiya N, Fujimura M, Sekita N, Mikami K, Hiruta N,Suzuki H
  • Journal Title: Jpn J Clin Oncol Volume: 45 Issue: 11 Pages: 1091-1095
  • DOI: 10.1093/jjco/hyv128
• [Journal Article] Nadir Testosterone after Long-Term Followup Predicts Prognosis in Patients with Prostate Cancer Treated with Combined Androgen Blockade. (2015)
  • Author(s): Kamada S, Sakamoto S, Ando K, Muroi A, Fuse M, Kawamura K, Imamoto T, Suzuki H, Nagata M, Nihei N, Akakura K, Ichikawa T.
  • Journal Title: Journal of Urology Volume: 194 Issue: 5 Pages: 1264-70
  • DOI: 10.1016/j.juro.2015.03.120
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Health-related quality of life after carbon-ion radiotherapy for prostate cancer: A 3-year prospective study. (2014)
  • Author(s): Katoh H, Tsuji H, Ishikawa H, Kamada T, Wakatsuki M, Hirasawa N, Suzuki H, Akakura K, Nakano T, Shimazaki J, Tsujii H.
  • Journal Title: Int J Urol. Volume: 21 Issue: 4 Pages: 370-5
  • DOI: 10.1111/iju.12294
  • Peer Reviewed
• [Journal Article] Loss of PTEN is associated with aggressive behavior in ERG positive prostate cancer (2014)
  • Author(s): Leinonen KA, Saram臾i OR, Furusato B, Kimura T, Takahashi H, Egawa S, Suzuki H, Keiger K, Hahm SH, Isaacs WB, Tolonen TT, Stenman UH, Tammela TLJ, Nykter M, Bova GS, Visakorpi T
  • Journal Title: Cancer Epidemiol Biomarkers Prev Volume: 印刷中 Issue: 12 Pages: 2333-2344
  • DOI: 10.1158/1055-9965.epi-13-0333-t
  • Peer Reviewed
• [Journal Article] Development of nomogram to non-steroidal antiandrogen sequential alternation in prostate cancer for predictive model. (2014)
  • Author(s): Kamiya N, Suzuki H, Nishimura K, Fujii M, Okegawa T, Matsuda T, Morita T, Takihana Y, Ozono S, Namiki M, Matsubara A, Ichikawa T, Miki T.
  • Journal Title: Jpn J Clin Oncol. Volume: 44 Issue: 3 Pages: 263-269
  • DOI: 10.1093/jjco/hyt230
  • Peer Reviewed
• [Journal Article] Usefulness of J-CAPRA Score for High-risk Prostate Cancer Patients Treated with Carbon Ion Radiotherapy Plus Androgen Deprivation Therapy. (2014)
  • Author(s): Akakura K, Tsuji H, Suzuki H, Ichikawa T, Ishikawa H, Okada T, Kamada T, Harada M, Tsujii H, Shimazaki J.
  • Journal Title: Jpn J Clin Oncol. Volume: 44 Issue: 4 Pages: 360-5
  • DOI: 10.1093/jjco/hyu006
  • Peer Reviewed / Open Access
• [Journal Article] Clinical outcomes by relative docetaxel dose and dose intensity as chemotherapy for Japanese patients with castration-resistant prostate cancer: A retrospective multi-institutional collaborative study (2013)
  • Author(s): Kamiya N, Suzuki H, Ueda T, Sato N, Nakatsu H, Mikami K, Sato N, Nomura K, Akakura K, Okano T, Ooki T, Naya Y, Ota S, Masai M, Ichikawa T.
  • Journal Title: Int J Clin Oncol. Volume: 19 Issue: 1 Pages: 157
  • DOI: 10.1007/s10147-012-0510-9
  • Peer Reviewed
• [Presentation] 前立腺癌診断のこれまでとこれから：『プロメーテウスの火』としてのPSA (2016)
  • Author(s): 鈴木啓悦
  • Organizer: 第620回日本泌尿器科学会東京地方会
  • Place of Presentation: 御茶ノ水ソラシティ（東京都・千代田区）
  • Year and Date: 2016-02-18
  • Invited
• [Presentation] 日本の進行性前立腺癌治療を考える：ガラパゴス化とグローバル化 (2015)
  • Author(s): 鈴木啓悦
  • Organizer: 第29回日本泌尿器内視鏡学会総会
  • Place of Presentation: 京王プラザホテル東京（東京都・新宿区）
  • Year and Date: 2015-11-19
  • Invited
• [Presentation] アンドロゲン環境から前立腺癌治療を考える：草食系男子と肉食系男子で治療は違うのか？ (2015)
  • Author(s): 鈴木啓悦
  • Organizer: 第67回日本泌尿器科学会西日本総会
  • Place of Presentation: 福岡国際会議場（福岡県・福岡市）
  • Year and Date: 2015-11-07
  • Invited
• [Presentation] 前立腺癌骨転移：Bone-dominant diseaseを考える (2015)
  • Author(s): 鈴木啓悦
  • Organizer: 日本泌尿器腫瘍学会第１回学術集会
  • Place of Presentation: 京都国際会議場（京都府・京都市）
  • Year and Date: 2015-11-01
  • Invited
• [Presentation] 去勢抵抗性前立腺癌の最適化治療：新規薬剤の開発 (2015)
  • Author(s): 鈴木啓悦，内海孝信，遠藤匠，岡了，李芳菁，加藤精二，宋本尚俊，若井健，西見大輔，高波眞佐治，矢野仁，上島修一，神谷直人
  • Organizer: 第53回日本癌治療学会学術集会
  • Place of Presentation: 京都国際会議場（京都府・京都市）
  • Year and Date: 2015-10-30
  • Invited
• [Presentation] Assessment of Arterial Stiffness Using Cardio-Ankle Vascular Index in Patients with Prostate Cancer Treated by a Short-Term of Androgen Deprivation Therapy. (2015)
  • Author(s): Oka R, Utumi T, Kamiya N, Lee F, Endo T, Yano M, Kamijima S, Nishimi D, Takanami M, Suzuki H
  • Organizer: SIU2015
  • Place of Presentation: Melbourne, Victoria, Australia
  • Year and Date: 2015-10-16
  • Int'l Joint Research
• [Presentation] Transcriptionally-Targeted Retroviral Replicating Vectors: A Novel Strategy for Gene Therapy of Prostate Caner. (2015)
  • Author(s): Kamijima S, Kimura T, Inagaki A, Hiraoka K, Haga K, Collins S, Hermann K, Kamiya N, Hacke K, Logg C, Kao C, Bochner B, Kasahara N, Suzuki H
  • Organizer: SIU2015
  • Place of Presentation: Melbourne, Victoria, Australia
  • Year and Date: 2015-10-16
  • Int'l Joint Research
• [Presentation] ドセタキセルのエビデンスと最適な患者像とは？ (2015)
  • Author(s): 神谷直人，内海孝信，遠藤匠，矢野仁，上島修一，西見大輔，高波眞佐治，鈴木啓悦
  • Organizer: 第80回日本泌尿器科学会東部総会
  • Place of Presentation: 京王プラザホテル東京（東京都・新宿区）
  • Year and Date: 2015-09-25
  • Invited
• [Presentation] Nadir Testosterone after Long-Term Follow-Up Predicts Prognosis of Prostate Cancer Patients Treated With Combined Androgen Blockade. (2015)
  • Author(s): Shuhei Kamada, Shinichi Sakamoto, Keisuke Ando, Ayumi Muroi, Miki Fuse, Koji Kawamura, Takashi Imamoto, Hiroyoshi Suzuki, Maki Nagata, Naoki Nihei, Koichiro Akakura, Tomohiko Ichikawa
  • Organizer: America Urological Association Annual Meeting 2015
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2015-05-19
  • Int'l Joint Research
• [Presentation] 進行性前立腺癌に対する骨マネジメント (2015)
  • Author(s): 鈴木啓悦
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: ホテル金沢（石川県・金沢市）
  • Year and Date: 2015-04-20
  • Invited
• [Presentation] Men’s Bone Healthを考える (2015)
  • Author(s): 鈴木啓悦
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: ANAクラウンプラザホテル金沢（石川県・金沢市）
  • Year and Date: 2015-04-18
  • Invited
• [Presentation] 日本人の日本人による日本人のためのCRPC治療を考える (2015)
  • Author(s): 鈴木啓悦
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 石川県立音楽堂（石川県・金沢市）
  • Year and Date: 2015-04-18
  • Invited
• [Presentation] 前立腺がんにおけるホルモン療法のパラダイム・シフト
  • Author(s): 鈴木啓悦
  • Organizer: がんセンター・多地点合同メディカル・カンファレンス
  • Place of Presentation: 茨城県笠間市 茨城県立中央病院
  • Invited
• [Presentation] 病期C前立腺癌症例に対するホルモン療法併用放射線療法
  • Author(s): 鈴木啓悦，岡了，李芳菁，内海孝信，遠藤匠，矢野仁，直井牧人，上島修一，西見大輔，高波眞佐治，神谷直人
  • Organizer: 第78回日本泌尿器科学会東部総会
  • Place of Presentation: 新潟県新潟市 朱雀メッセ
  • Invited
• [Presentation] Validation of active surveillance criteria for pathological insignificant prostate cancer in Japanese men
  • Author(s): Yamada Y, Sakamoto S, Sazuka T, Goto Y, Yanagisawa M, Kawamura K, Kamiya N, Imamoto T, Nihei N, Suzuki H, Sato N, Ichikawa T
  • Organizer: The 4th congress of Asian Pacific Prostate Society
  • Place of Presentation: 沖縄県那覇市 万国津梁館
• [Presentation] Prodrug-activator gene therapy using prostate-targeted retroviral replicating vectors
  • Author(s): Kamijima S, Kimura T, Haga K, Hiraoka K, Inagaki A, Tam Q, Logg CR, Kao C, Bochner BH, Suzuki H, Kasahara N, Ichikawa T
  • Organizer: The 4th congress of Asian Pacific Prostate Society
  • Place of Presentation: 沖縄県那覇市 万国津梁館
• [Presentation] Prostate cancer sequencing: Locally advanced prostate cancer
  • Author(s): Suzuki H
  • Organizer: The 4th congress of Asian Pacific Prostate Society
  • Place of Presentation: 沖縄県那覇市 万国津梁館
  • Invited
• [Presentation] Clinical outcomes by relative docetaxel dose and dose intensity as chemotherapy with castration-resistant prostate cancer: A retrospective multi-institutional collaborative study
  • Author(s): Kamiya N, Suzuki H, Ueda T, Nakatsu H, Sato N, Mikami K, Sato N, Ichikawa T
  • Organizer: American Urological Association Annual meeting
  • Place of Presentation: 米国San Diego Convention Center
• [Remarks] 東邦大学医療センター佐倉病院泌尿器科
  • URL: http://www.lab.toho-u.ac.jp/med/sakura/urology/
• [Remarks] 東邦大学医療センター佐倉病院泌尿器科ホームページ
  • URL: http://www.lab.toho-u.ac.jp/med/sakura/urology/