Development of precision medicine for the therapy to metastatic prostate cancer using genome-eide SNP array

• Project/Area Number: 17K11145
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kyushu University
• Principal Investigator: Shiota Masaki 九州大学, 大学病院, 講師 (20635445)
• Co-Investigator(Kenkyū-buntansha): 江藤 正俊 九州大学, 医学研究院, 教授 (90315078)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 転移性前立腺癌 / 一塩基多型 / 個別化医療

Outline of Final Research Achievements

Hormone therapy is widely used for prostate cancer. However, the effect varies greatly among individuals. Therefore, in order to clarify the genetic background among individuals related to the therapeutic effect of hormone therapy, we investigated the relationship between gene polymorphism and the effect of hormone therapy. As a result, it was revealed that polymorphisms of some genes related to androgen metabolism are associated with therapeutic effect.

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、ホルモン療法中のアンドロゲン代謝の個人差がホルモン療法の治療効果に影響していることが示された。また、今後のゲノムワイド解析の結果を含めて、遺伝子多型がホルモン療法の個別化治療に応用できる可能性が示唆された。

Research Products

• [Journal Article] Genetic Polymorphism in Sex Hormone-binding Globulin With a Prognosis of Androgen Deprivation Therapy in Metastatic Prostate Cancer Among Japanese Men (2019)
  • Author(s): Shiota M, Fujimoto N, Tsukahara S, Ushijima M, Takeuchi A, Kashiwagi E, Inokuchi J, Tatsugami K, Uchiumi T, Eto M
  • Journal Title: Clinical Genitourinary Cancer Volume: 17 Issue: 3 Pages: e387-e393
  • DOI: 10.1016/j.clgc.2019.03.021
  • Peer Reviewed
• [Journal Article] The impact of genetic polymorphism on CYP19A1 in androgen-deprivation therapy among Japanese men (2019)
  • Author(s): Shiota M, Fujimoto N, Tsukahara S, Ushijima M, Takeuchi A, Kashiwagi E, Inokuchi J, Tatsugami K, Uchiumi T, Eto M
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: 83 Issue: 5 Pages: 933-938
  • DOI: 10.1007/s00280-019-03811-8
  • Peer Reviewed
• [Journal Article] Association of Missense Polymorphism in HSD3B1 With Outcomes Among Men With Prostate Cancer Treated With Androgen-Deprivation Therapy or Abiraterone (2019)
  • Author(s): Shiota Masaki、Narita Shintaro、Akamatsu Shusuke、Fujimoto Naohiro、Sumiyoshi Takayuki、Fujiwara Maki、Uchiumi Takeshi、Habuchi Tomonori、Ogawa Osamu、Eto Masatoshi
  • Journal Title: JAMA Network Open Volume: 2 Issue: 2 Pages: e190115-e190115
  • DOI: 10.1001/jamanetworkopen.2019.0115
  • Peer Reviewed / Open Access
• [Journal Article] Serum testosterone level as possible predictive marker in androgen receptor axis-targeting agents and taxane chemotherapies for castration-resistant prostate cancer (2019)
  • Author(s): Shiota Masaki、Kashiwagi Eiji、Murakami Tomohiko、Takeuchi Ario、Imada Kenjiro、Inokuchi Junichi、Tatsugami Katsunori、Eto Masatoshi
  • Journal Title: Urologic Oncology: Seminars and Original Investigations Volume: 37 Issue: 3 Pages: 180.e19-180.e24
  • DOI: 10.1016/j.urolonc.2018.10.020
  • Peer Reviewed
• [Journal Article] Mineralocorticoid receptor signaling affects therapeutic effect of enzalutamide (2018)
  • Author(s): Shiota Masaki、Fujimoto Naohiro、Higashijima Katuyoshi、Imada Kenjiro、Kashiwagi Eiji、Takeuchi Ario、Inokuchi Junichi、Tatsugami Katsunori、Kajioka Shunichi、Uchiumi Takeshi、Eto Masatoshi
  • Journal Title: The Prostate Volume: 78 Issue: 14 Pages: 1045-1052
  • DOI: 10.1002/pros.23661
  • Peer Reviewed
• [Journal Article] Collateral resistance to taxanes in enzalutamide-resistant prostate cancer through aberrant androgen receptor and its variants (2018)
  • Author(s): Shiota Masaki、Dejima Takashi、Yamamoto Yoshiaki、Takeuchi Ario、Imada Kenjiro、Kashiwagi Eiji、Inokuchi Junichi、Tatsugami Katsunori、Kajioka Shunichi、Uchiumi Takeshi、Eto Masatoshi
  • Journal Title: Cancer Science Volume: 109 Issue: 10 Pages: 3224-3234
  • DOI: 10.1111/cas.13751
  • Peer Reviewed / Open Access
• [Journal Article] Serum testosterone before and during androgen-deprivation therapy, and prognosis between cigarette smokers and nonsmokers with metastatic prostate cancer (2018)
  • Author(s): Shiota Masaki、Kashiwagi Eiji、Murakami Tomohiko、Takeuchi Ario、Imada Kenjiro、Inokuchi Junichi、Tatsugami Katsunori、Eto Masatoshi
  • Journal Title: Andrologia Volume: 50 Issue: 10 Pages: e13119-e13119
  • DOI: 10.1111/and.13119
  • Peer Reviewed
• [Journal Article] The Association of Polymorphisms in the Gene Encoding Gonadotropin-Releasing Hormone with Serum Testosterone Level during Androgen Deprivation Therapy and Prognosis of Metastatic Prostate Cancer. (2018)
  • Author(s): Shiota M, Fujimoto N, Takeuchi A, Kashiwagi E, Dejima T, Inokuchi J, Tatsugami K, Yokomizo A, Kajioka S, Uchiumi T, Eto M.
  • Journal Title: The Journal of Urology Volume: 199 Issue: 3 Pages: 734-740
  • DOI: 10.1016/j.juro.2017.09.076
  • Peer Reviewed
• [Journal Article] Gene Polymorphism-related Individual and Interracial Differences in the Outcomes of Androgen Deprivation Therapy for Prostate Cancer. (2017)
  • Author(s): Fujimoto N, Shiota M, Tomisaki I, Minato A.
  • Journal Title: Clinical Genitourinary Cancer Volume: 15 Issue: 3 Pages: 337-342
  • DOI: 10.1016/j.clgc.2017.01.006
  • Peer Reviewed
• [Presentation] 日本人転移性前立腺癌におけるCYP19A1遺伝子多型とホルモン療法の予後 (2019)
  • Author(s): 塩田真己、藤本直浩、塚原茂大、牛島美保、武内在雄、柏木英志、猪口淳一、立神勝則、内海健、江藤正俊
  • Organizer: 第3回リキッドバイオプシー研究会
• [Presentation] HSD3B1遺伝子多型の一次ホルモン療法およびアビラテロン治療における意義 (2019)
  • Author(s): 塩田真己、成田伸太郎、赤松秀輔、藤本直浩、住吉崇幸、藤原真希、内海健、羽渕友則、小川修、江藤正俊
  • Organizer: 第107回日本泌尿器科学会総会
• [Presentation] アビラテロン代謝酵素HSD3B1とSRD5A2による去勢抵抗性前立腺癌に対するアビラテロン治療の予後予測 (2019)
  • Author(s): 塩田真己, 赤松秀輔, 成田伸太郎, 住吉崇幸, 藤原真希, 内海健, 小川修, 羽渕友則, 江藤正俊
  • Organizer: 第5回日本泌尿器腫瘍学会学術集会
• [Presentation] 前立腺癌薬物療法の個別化医療に向けた遺伝子多型研究 (2019)
  • Author(s): 塩田真己、成田伸太郎、赤松秀輔、藤本直浩、羽渕友則、小川修、江藤正俊
  • Organizer: 第28回泌尿器科分子・細胞研究会
  • Invited
• [Presentation] Treatment resistance due to aberrant androgen signaling in advanced prostate cancer (2019)
  • Author(s): Shiota M, Eto M
  • Organizer: 第78回日本癌学会学術総会
  • Invited
• [Presentation] ゲノム診断と 新規治療法の展望 (2019)
  • Author(s): 塩田真己
  • Organizer: 第71回日本泌尿器科学会西日本総会
  • Invited
• [Presentation] アンドロゲン代謝システムに着目した 前立腺癌の進展・薬物応答の研究最前線 (2019)
  • Author(s): 塩田真己
  • Organizer: 第35回前立腺シンポジウム
  • Invited
• [Presentation] Missense polymorphism in HSD3B1 in Japanese men treated with primary androgen-deprivation therapy for metastatic prostate cancer (2018)
  • Author(s): Shiota M, Fujimoto N, Imada K, Kashiwagi E, Takeuchi A, Inokuchi J, Tatsugami K, Kajioka S, Eto M
  • Organizer: 2018 ASCO Annual Meeting
  • Int'l Joint Research
• [Presentation] 転移性前立腺癌におけるCYP19A1遺伝子多型とホルモン療法中の血清テストステロン値およびホルモン療法の予後 (2018)
  • Author(s): 塩田真己、藤本直浩、塚原茂大、牛島美保、武内在雄、柏木英志、猪口淳一、立神勝則、内海健、江藤正俊
  • Organizer: 第24回国際個別化医療学会
• [Presentation] 前立腺癌薬物療法の個別化医療に向けた遺伝子多型解析 (2018)
  • Author(s): 塩田真己
  • Organizer: 第5回前立腺生物学シンポジウム
  • Invited
• [Presentation] Up-to-date on the mechanism of castration resistance in prostate cancer (2018)
  • Author(s): Masaki Shiota, Masatoshi Eto
  • Organizer: 第77回日本癌学会学術総会
  • Invited
• [Presentation] 前立腺癌薬物療法の個別化医療 (2018)
  • Author(s): 塩田真己
  • Organizer: 第70回日本泌尿器科学会西日本総会
  • Invited
• [Presentation] 前立腺癌薬物療法の個別化医療に向けた遺伝子多型研究 (2018)
  • Author(s): 塩田真己、成田伸太郎、赤松秀輔、藤本直浩、羽渕友則、小川修、江藤正俊
  • Organizer: 第28回泌尿器科分子・細胞研究会
  • Invited
• [Presentation] Precision medicine in metastatic castration-sensitive prostate cancer (2017)
  • Author(s): Masaki Shiota
  • Organizer: 2017 International Conference of Clinical and Basic Research for Prostate Disease
  • Int'l Joint Research / Invited
• [Presentation] 泌尿器癌のPrecision Medicine の確立に向けた取り組み (2017)
  • Author(s): 塩田真己
  • Organizer: 第69回日本泌尿器科学会西日本総会
  • Invited
• [Presentation] The association of polymorphism in gonadotropin releasing hormone with serum testosterone level during androgen-deprivation therapy and prognosis in metastatic prostate cancer (2017)
  • Author(s): Shiota M, Fujimoto N, Takeuchi A, Kashiwagi E, Dejima T, Inokuchi J, Tatsugami K, Yokomizo A, Uchiumi T, Eto M
  • Organizer: 2017 ASCO Annual Meeting
  • Int'l Joint Research
• [Presentation] 転移性前立腺癌におけるHSD3B1多型とホルモン療法の予後 (2017)
  • Author(s): 塩田真己、藤本直浩、今田憲二郎、柏木英志、武内在雄、猪口淳一、立神勝則、梶岡俊一、内海健、江藤正俊
  • Organizer: 第2回リキッドバイオプシー研究会
• [Presentation] Independent validation of missense polymorphism in HSD3B1 in Japanese men treated with primary androgen-deprivation therapy for metastatic prostate cancer (2017)
  • Author(s): Shiota M, Fujimoto N, Imada K, Kashiwagi E, Takeuchi A, Inokuchi J, Tatsugami K, Kajioka S, Uchiumi T, Eto M
  • Organizer: 2018 ASCO Genitourinary Cancers Symposium
  • Int'l Joint Research
• [Book] Hormone Therapy and Castration Resistance of Prostate Cancer (2018)
  • Author(s): Masaki Shiota
  • Total Pages: 350
  • Publisher: Springer
  • ISBN: 9789811070136
• [Patent(Industrial Property Rights)] 膀胱癌治療におけるＢＣＧ膀胱内注入療法に対する抵抗性を予測するため のバイオマーカー (2019)
  • Inventor(s): 塩田真己, 江藤正俊
  • Industrial Property Rights Holder: 塩田真己, 江藤正俊
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019