Elucidation of castration-resistant prostate cancer mechanism via hedgehog pathway

• Project/Area Number: 18K16716
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Osaka Medical College
• Principal Investigator: Ibuki Naokazu 大阪医科大学, 医学部, 講師 (90368100)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 去勢抵抗性前立腺癌 / Enzalutamide / Hedgehog / Hedgehog pathway

Outline of Final Research Achievements

Pharmacotherapy for castration-resistant prostate cancer has been developing in recent years with the advent of new drugs. However, the drug will eventually become ineffective and new drugs are expected to appear.
Our study suggests that the Hedgehog pathway may be involved in Enzalutamide resistance, one of the drug therapies for castration-resistant prostate cancer, and will lead to the development of new drugs for castration-resistant prostate cancer. It was considered.

Academic Significance and Societal Importance of the Research Achievements

去勢抵抗性前立腺癌のメカニズムおよび去勢抵抗性前立腺癌に対する薬物療法（Enzalutamide）抵抗性のメカニズムを検討するため、癌細胞を用いてHedgehog経路が関与しているかどうかの実験を行った。
結果、Hedgehog経路を抑制することで去勢抵抗性前立腺癌およびEnzalutamide抵抗性前立腺癌に対して治療効果が発揮されることを確認した。今後の新薬開発につながるものと考えられる。

Research Products

• [Journal Article] Comparison of Radiographic Progression-Free Survival and PSA Response on Sequential Treatment Using Abiraterone and Enzalutamide for Newly Diagnosed Castration-Resistant Prostate Cancer: A Propensity Score Matched Analysis from Multicenter Cohort. (2019)
  • Author(s): Komura K,Fujiwara Y,UchimotoT,Saito K,Tanda N,Matsunaga T, Ichihashi A,Tsutsumi T, Tsujino T,Yoshikawa Y,Nishimoto Y,Takai T,Minami K,Taniguchi K,Tanaka T, Uehara H,Hirano H,Nomi H,Ibuki N, Takahara K,Inamoto T,Azuma H.
  • Journal Title: J. Clin. Med. Volume: 8(8) Issue: 8 Pages: 1251-1251
  • DOI: 10.3390/jcm8081251
  • Peer Reviewed / Open Access
• [Journal Article] The CANLPH Score, an Integrative Model of Systemic Inflammation and Nutrition Status (SINS), Predicts Clinical Outcomes After Surgery in Renal Cell Carcinoma: Data From a Multicenter Cohort in Japan. (2019)
  • Author(s): Komura K,Hashimoto T, Tsujino T, Muraoka R, Tsutsumi T, Satake N, Matsunaga T, Yoshikawa Y, Takai T, Minami K, Taniguchi K, Uehara H, Tanaka T, Hirano H, Nomi H, Ibuki N, Takahara K, Inamoto T, Ohno Y, Azuma H.
  • Journal Title: Ann Surg Oncol. Volume: 26(9) Issue: 9 Pages: 2994-3004
  • DOI: 10.1245/s10434-019-07530-5
  • Peer Reviewed / Open Access
• [Journal Article] A Panel of MicroRNA Signature as a Tool for Predicting Survival of Patients with Urothelial Carcinoma of the Bladder (2018)
  • Author(s): Inamoto Teruo、Uehara Hirofumi、Akao Yukihiro、Ibuki Naokazu、Komura Kazumasa、Takahara Kiyoshi、Takai Tomoaki、Uchimoto Taizo、Saito Kenkichi、Tanda Naoki、Yoshikawa Yuki、Minami Koichiro、Hirano Hajime、Nomi Hayahito、Kato Ryuji、Hayashi Tetsuya、Azuma Haruhito
  • Journal Title: Disease Markers Volume: 2018 Pages: 1-6
  • DOI: 10.1155/2018/5468672
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] hibition controls aggressive prostate tumors deficient in Y-linked histone demethylase KDM5D. (2018)
  • Author(s): Komura K、Yoshikawa Y, Shimamura T, Chakraborty G, Gerke TA, Hinohara K, Chadalavada K, Jeong SH, Armenia J, Du SY, Mazzu YZ, Taniguchi K, Ibuki N, Meyer CA, Nanjangud GJ, Inamoto T, Lee GM, Mucci LA, Azuma H, Sweeney CJ, Kantoff PW.
  • Journal Title: Journal of Clinical Investigation Volume: 128(7) Issue: 7 Pages: 2979-95
  • DOI: 10.1172/jci96769
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Treatment outcome of dose reduction of enzalutamide against CRPC? (2019)
  • Author(s): Ibuki N, Inamoto T,Ichihashi A,Uehara H,Komura K,Hirano H,Nomi H,Azma H.
  • Organizer: AUA 2019
  • Int'l Joint Research
• [Presentation] プラチナ抵抗性尿路上皮癌に対するPembrolizumabの治療効果予測因子の検討 (2019)
  • Author(s): 伊夫貴 直和、稲元輝生、内本泰三、辻野拓也、南 幸一郎、光野絢子、高木 志寿子、木下将宏、徳永雄希、土井 由紀子、中森啓太、木山 賢、東 治人.
  • Organizer: 第107回日本泌尿器科学会総会
• [Presentation] 当施設における腎細胞癌に対するpresurgical therapyの臨床的検討 (2019)
  • Author(s): 伊夫貴 直和、稲元輝生、小村和正、上原博史、平野 一、能見勇人、東 治人.
  • Organizer: 日本泌尿器腫瘍学会 第5回学術集会
• [Presentation] ハイリスクホルモン感受性転移性前立腺癌に対するAbiraterone acetateとPrednisolone併用療法の治療効果 (2019)
  • Author(s): 伊夫貴 直和、稲元輝生、西本優大、内本泰三、光野絢子、藤川正弘、土井 亘、宮下 由紀恵、木村亮輔、小山耕平、木山 賢、和辻利和、東 治人.
  • Organizer: 第69回日本泌尿器科学会中部総会
• [Presentation] 生体腎移植前のドナー検査において腫瘍性病変が指摘され、根治的治療が可能であった3症例 (2019)
  • Author(s): 上原博史、平野 一、岡部知太、木村孝平、寺本昌司、高倉一平、西村一希、木下将宏、徳永雄希、中森啓太、市橋 淳、谷口俊理、小林大介、堤 岳之、小村和正、伊夫貴 直和、稲元輝生、能見勇人、東 治人.
  • Organizer: 第53回日本臨床腎移植学会