Action mechanisms responsible for the development of resistance to endocrine therapy in breast cancer and overcoming the resistance: focusing on a role of breast cancer stem cells

• Project/Area Number: 26461964
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kawasaki Medical School
• Principal Investigator: Junichi Kurebayashi 川崎医科大学, 医学部, 教授 (10248255)
• Co-Investigator(Kenkyū-buntansha): 森谷 卓也 川崎医科大学, 医学部, 教授 (00230160) ; 鹿股 直樹 川崎医科大学, 医学部, 准教授 (60263373)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 乳癌 / 癌幹細胞 / エストロゲン / ヘッジホッグシグナル / 内分泌療法抵抗性 / GANT61 / 抗エストロゲン薬 / 細胞増殖抑制 / GLI / Hedgehogシグナル / Gli1

Outline of Final Research Achievements

Most breast cancers are estrogen-dependent and sensitive to endocrine therapy. However, resistance to endocrine therapy occurs and makes endocrine therapy ineffective. We focused on a role of breast cancer stem cells in the development of the resistance. Regulatory mechanisms of estrogen on breast cancer stem cells were investigated in vitro. We found that estrogen regulates breast cancer stem cells through estrogen receptor and hedgehog signaling pathway.

Research Products

• [Journal Article] Anti-cancer stem cell activity of a non-canonical hedgehog inhibitor GANT61 in estrogen receptor-positive breast cancer cells. (2017)
  • Author(s): Junichi Kurebayashi, Yoshikazu Koike, Yusuke Ohta, Wataru Saitoh, Tetsumasa Yamashita, Naoki Kanomata, Takuya Moriya
  • Journal Title: Cancer Science Volume: in press Issue: 5 Pages: 918-930
  • DOI: 10.1111/cas.13205
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Anti-cell growth and anti-cancer stem cell activities of the non-canonical hedgehog inhibitor GANT61 in triple-negative breast cancer cells. (2017)
  • Author(s): Yoshikazu Koike, Yusuke Ohta, Wataru Saitoh, Tetsumasa Yamashita, Naoki Kanomata, Takuya Moriya, Junichi Kurebayashi
  • Journal Title: Breast Cancer Volume: in press Issue: 5 Pages: 683-693
  • DOI: 10.1007/s12282-017-0757-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Antitumor and anticancer stem cell activities of eribulin mesylate and antiestrogens in breast cancer cells. (2015)
  • Author(s): Kurebayashi J, Kanomata N, Yamashita T, Shimo T, Moriya T.
  • Journal Title: Breast Cancer Volume: 未定 Issue: 3 Pages: 425-436
  • DOI: 10.1007/s12282-014-0580-9
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic value of phosphorylated HER2 in HER2-positive breast cancer patients treated with adjuvant trastuzumab. (2015)
  • Author(s): Kurebayashi J, Kanomata N, Yamashita T, Shimo T, Mizutoh A, Moriya T, Sonoo H.
  • Journal Title: Breast Cancer Volume: 22 Issue: 3 Pages: 292-299
  • DOI: 10.1007/s12282-013-0478-y
  • Peer Reviewed
• [Journal Article] Clinicopathological characteristics of breast cancer and trends in the management of breast cancer patients in Japan: Based on the Breast Cancer Registry of the Japanese Breast Cancer Society between 2004 and 2011. (2015)
  • Author(s): Kurebayashi J, Miyoshi Y, Ishikawa T, Saji S, Sugie T, Suzuki T, Takahashi S, Nozaki M, Yamashita H, Tokuda Y, Nakamura S
  • Journal Title: Breast Cancer Volume: 22 Issue: 3 Pages: 235-244
  • DOI: 10.1007/s12282-015-0599-6
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Metastasis-associated MCL1 and P16 copy number alterations dictate resistance to vemurafenib in a BRAFV600E patient-derived papillary thyroid carcinoma preclinical model. (2015)
  • Author(s): Duquette M, Sadow PM, Fischer A, Song C, Husain A, Rizaldos EC, Makrogiorgos M, Kurebayashi J, Nose V, Van Hummelen P, Bronson RT, Dias-Santagata D, Pandolfi PP, Nucera C
  • Journal Title: Oncotarget Volume: 6 Issue: 40 Pages: 42445-42467
  • DOI: 10.18632/oncotarget.6442
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The cell cycle profiling-risk score based on CDK1 and 2 predicts early recurrence in node-negative, hormone receptor-positive breast cancer treated with endocrine therapy. (2014)
  • Author(s): Kim SJ, Masuda N, Tsukamoto F, Inaji H, Akiyama F, Sonoo H, Kurebayashi J, Yoshidome K, Tsujimoto M, Takei H, Masuda S, Nakamura S, Noguchi S.
  • Journal Title: Cancer Lett. Volume: 355 Issue: 2 Pages: 217-223
  • DOI: 10.1016/j.canlet.2014.08.042
  • Peer Reviewed / Open Access
• [Presentation] Anti-cancer stem cell activity of the hedgehog inhibitor GANT61 in ER-positive breast cancer cells. (2017)
  • Author(s): Junichi Kurebayashi, Yoshikazu Koike, Yusuke Ohta, Wataru Saitoh, Tetsumasa Yamashita, Naoki Kanomata, Takuya Moriy
  • Organizer: The 15th St. Gallen International Breast Cancer Conference
  • Place of Presentation: ウィーン（オーストリア）
  • Year and Date: 2017-03-16
  • Int'l Joint Research
• [Presentation] Anti-cancer stem cell activity of the hedgehog inhibitor GANT61 in triple-negative breast cancer cells (2017)
  • Author(s): Yoshikazu Koike, Yusuke Ohta, Wataru Saitoh, Tetsumasa Yamashita, Naoki Kanomata, Takuya Moriya, Junichi Kurebayashi
  • Organizer: The 15th St. Gallen International Breast Cancer Conference
  • Place of Presentation: ウィーン（オーストリア）
  • Year and Date: 2017-03-16
  • Int'l Joint Research
• [Presentation] Anti-cell growth and anti-cancer stem cell activities of the non-canonical hedgehog inhibitor GANT61 and antiestrogens in estrogen receptor-positive breast cancer cells. (2016)
  • Author(s): Junichi Kurebayashi, Yoshikazu Koike, Yusuke Ohta, Wataru Saitoh, Tetsumasa Yamashita, Naoki Kanomata, Takuya Moriya
  • Organizer: The 14th Breast Cancer Frontier Meeting
  • Place of Presentation: ホテル椿山荘東京（東京）
  • Year and Date: 2016-11-19
  • Int'l Joint Research / Invited
• [Presentation] ヘッジホッグシグナル伝達阻害薬GANT61及び抗エストロゲン薬のホルモン感受性乳癌細胞に対する抗腫瘍効果及び癌幹細胞制御作用． (2016)
  • Author(s): 紅林 淳一、小池 良和、太田 祐介、斎藤 亙、鹿股 直樹
  • Organizer: 第25回乳癌基礎研究会
  • Place of Presentation: 市立奈良病院（奈良）
  • Year and Date: 2016-07-23
• [Presentation] ヘッジホッグシグナル伝達阻害薬GANT61のホルモン感受性乳癌細胞に対する抗腫瘍効果及び癌幹細胞制御に関する基礎的研究 (2016)
  • Author(s): 紅林淳一、小池良和、太田祐介、山下哲正、斎藤亙、鹿股直樹、森谷卓也
  • Organizer: 第24回日本乳癌学会学術総会
  • Place of Presentation: 東京ビッグサイト（東京）
  • Year and Date: 2016-06-17
• [Presentation] 乳癌治療におけるアロマターゼ阻害薬の役割． (2016)
  • Author(s): 紅林淳一
  • Organizer: 第23回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 倉敷芸文館（倉敷）
  • Year and Date: 2016-01-15
  • Invited
• [Presentation] 乳癌内分泌療法抵抗性発生のメカニズムの解明とその克服を目指した基礎研究． (2015)
  • Author(s): 紅林 淳一、鹿股 直樹 、下 登志朗、山下 哲正
  • Organizer: 第6回川崎医科大学学術集会
  • Place of Presentation: 川崎医科大学（倉敷）
  • Year and Date: 2015-08-01
• [Presentation] エストロゲンによる乳癌幹細胞の制御と内分泌療法抵抗性に関する基礎的研究. (2015)
  • Author(s): 紅林淳一、小池良和、太田裕介、山下哲正、鹿股直樹
  • Organizer: 第16回ホルモンと癌研究会
  • Place of Presentation: 朝日大学村上記念病院（岐阜）
  • Year and Date: 2015-07-10
• [Presentation] 乳癌治療薬による癌幹細胞の制御機構に関する基礎的研究． (2015)
  • Author(s): 紅林淳一、鹿股直樹、下登志朗、山下哲正、小池良和、太田裕介、森谷卓也
  • Organizer: 第23回日本乳癌学会学術総会
  • Place of Presentation: 東京国際フォーラム（東京）
  • Year and Date: 2015-07-03
  • Invited
• [Presentation] Anti-tumor and anti-cancer stem cell activities of eribulin and anti-estrogens in breast cancer cells. (2015)
  • Author(s): J. Kurebayashi, N. Kanomata, T. Yamashita, T. Shimo, T. Moriya
  • Organizer: 第14回ザンクトガレン国際乳癌会議
  • Place of Presentation: オーストリア・ウィーン オーストリアセンター
  • Year and Date: 2015-03-19
• [Presentation] エリブリンと内分泌療法薬の同時併用効果に関する基礎的検討． (2014)
  • Author(s): 紅林淳一、鹿股直樹、山下哲正、下登志朗、森谷卓也
  • Organizer: 第23回乳癌基礎研究会
  • Place of Presentation: 茨城県つくば市筑波山ホテル青木屋
  • Year and Date: 2014-07-26
• [Presentation] エストロゲン感受性乳癌細胞におけるエストロゲンの癌幹細胞制御機構． (2014)
  • Author(s): 紅林淳一、鹿股直樹、山下哲正、下登志朗、野村長久、森谷卓也
  • Organizer: 第15回ホルモンと癌研究会
  • Place of Presentation: 宮城県仙台市東北大学医学部艮陵会館
  • Year and Date: 2014-07-04
• [Book] オンコロジークリニカルガイド乳癌薬物療法改訂2版 (2016)
  • Author(s): 紅林淳一
  • Total Pages: 12
  • Publisher: 南山堂
• [Book] これからの乳癌診療2014-2015 (2014)
  • Author(s): 紅林淳一
  • Total Pages: 5
  • Publisher: 金原出版
• [Remarks] 川崎医科大学ホームページ教員情報
  • URL: http://kwweb-res.kawasaki-m.ac.jp/kwmhp/KgApp?section=13&kyoinId=ymkiyoooggo