A novel treatment strategy for castration-refractory prostate cancer targeting cross-talk between NF-kB and an intranuclear steroid receptor superfamily

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kanazawa University
• Principal Investigator: KONAKA Hiroyuki 金沢大学, 大学病院, 講師 (40334768)
• Co-Investigator(Kenkyū-buntansha): KITAGAWA Yasuhide 金沢大学, 大学病院, 講師 (00452102) ; KADONO Yoshifumi 金沢大学, 大学病院, 助教 (10397218) ; KYO Satoru 金沢大学, 医学系, 准教授 (50272969)
• Project Period (FY): 2011 – 2013
• Keywords: 去勢抵抗性前立腺癌 / 核内受容体 / NF-κB / クロストーク / アンドロゲン受容体 / エストロゲン受容体 / グルココルチコイド受容体 / シグナル伝達

Research Abstract

Elucidating a comprehensive mechanism through which most patients with advanced prostate cancer have an initial response to androgen deprivation therapy, but eventually progress to a castration-resistant state is critical to establish a novel treatment strategy for castration refractory prostate cancer (CRPC). We investigate the mechanism of CRPC from the perspective of some cross-talks in signal transduction pathway between NF-kB and an intranuclear steroid receptor superfamily containing androgen receptor, glucocorticoid receptor, and estrogen receptor. Also we target the cross-talk with various methods of inhibiting the signaling transduction pathway and established the integrated treatment strategy of CRPC. Consequently, our study made it clear that cross-talk between NF-kB and an intranuclear steroid receptor superfamily might existence, and also suggested inhibiting the cross-talk of signaling pathway network might be novel therapeutics for the management of CRPC.

Research Products

• [Journal Article] Repression of cell proliferation and androgen receptor activity in prostate cancer cells by 2'-hydroxyflavanone (2013)
  • Author(s): Ofude M, Mizokami A, Kumaki M, Izumi K, Konaka H, Kadono Y, Kitagawa Y, Shin M, Zhang J, Keller ET, Namiki M
  • Journal Title: Anticancer Res Volume: 33(10) Pages: 61-4453
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24123015
• [Journal Article] Exogenous SPARC suppresses proliferation and migration of prostate cancer by interacting with integrinβ1 (2013)
  • Author(s): Shin M, Mizokami A, Kim J, Ofude M, Konaka H, Kadono Y, Kitagawa Y, Miwa S, Kumaki M, Keller ET, Namiki M
  • Journal Title: Prostate Volume: 73(11) Pages: 70-1159
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/23532895
• [Journal Article] Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial (2012)
  • Author(s): Konaka H, Egawa S, Saito S, Yorozu A, Takahashi H, Miyakoda K, Fukushima M, Dokiya T, Yamanaka H, Stone NN, Namiki M
  • Journal Title: BMC Cancer Volume: 12 Pages: 110
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22439742
• [Journal Article] Increases in bone turnover marker levels at an early phase after starting zoledronic acid predicts skeletal-related events in patients with prostate cancer with bone metastasis (2012)
  • Author(s): Izumi K, Mizokami A, Itai S, Shima T, Shigehara K, Miwa S, Maeda Y, Konaka H, Koh E, Namiki M
  • Journal Title: BJU Int Volume: 109(3) Pages: 394-400
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21599822
• [Journal Article] What is appropriate neoadjuvant/adjuvant androgen deprivation for high-risk/locally advanced prostate cancer? (2011)
  • Author(s): Namiki M, Konaka H. Asian J
  • Journal Title: Androl Volume: 13(4) Pages: 5-624
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21642996
• [Presentation] Effect of adrenal androgens and HSD17B5 inhibitors on androgen receptor activity in prostate cancer microenvironment (2011)
  • Author(s): 熊木美紗子,溝上敦,金延任,島崇,大筆光夫,角野佳史,小中弘之,北川育秀,申珉京,並木幹夫
  • Organizer: 第70回日本癌治療学会総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 20111003-05