Verification of new therapeutic strategies for androgen receptor positive triple-negative breast cancer

• Project/Area Number: 17H07023
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Osaka City University
• Principal Investigator: ASANO YUKA 大阪市立大学, 大学院医学研究科, 後期臨床研究医 (10806376)
• Research Collaborator: KASHIWAGI Shinichiro
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: トリプルネガティブ乳癌 / アンドロゲン受容体 / 腫瘍微小環境 / 腫瘍免疫 / アンドロゲン / 個別化治療

Outline of Final Research Achievements

In this study, we clarified the usefulness of CDK4/6 inhibitors and antiandrogens in “Verification of new therapeutic strategies in androgen receptor (AR) positive triple negative breast cancer (TNBC)”. The molecular mechanism was also examined from the aspect of tumor immunity and epithelial-mesenchymal transition (EMT). In the future, we will promote basic research and clinical research for the purpose of constructing a new therapeutic strategy for AR-positive TNBC applicable to clinical practice. Specifically, we will continue our research as "A new breast cancer treatment strategy with CDK4/6 inhibitors captured from androgen signaling" (JSPS Young research B: 19K18038).

Academic Significance and Societal Importance of the Research Achievements

本研究では，AR陽性TNBCの代謝競合と免疫微小環境変化についての検証を行った．具体的には抗アンドロゲン剤やCDK4/6阻害剤，あるいはEMT抑制作用が報告されている微小管阻害剤 (エリブリン) の修飾による腫瘍免疫微小環境の動的な変化を代謝競合から捉え，分子生物学的に明らかにした．今後は，殺細胞性抗癌剤，分子標的治療薬，内分泌療法，免疫療法など，これらの組み合わせにより更なる効果が期待できる治療選択肢を検索し，臨床応用への一助としたい (併用療法の可能性の検証)．

Research Products

• [Journal Article] Clinical verification of the relationship between smoking and the immune microenvironment of breast cancer (2019)
  • Author(s): Takada Koji、Kashiwagi Shinichiro、Asano Yuka、Goto Wataru、Takahashi Katsuyuki、Fujita Hisakazu、Takashima Tsutomu、Tomita Shuhei、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: Journal of Translational Medicine Volume: 17 Issue: 1 Pages: 13-13
  • DOI: 10.1186/s12967-019-1773-y
  • Peer Reviewed / Open Access
• [Journal Article] Adenoid cystic carcinoma of the breast: a case report. (2019)
  • Author(s): Asano Y, Kashiwagi S, Sayaka T, Kuwae Y, Takashima T, Ohsawa M, Hirakawa K, Ohira M.
  • Journal Title: BMC Surgery Volume: 19 Issue: 1 Pages: 30-30
  • DOI: 10.1186/s12893-019-0494-8
  • Open Access
• [Journal Article] Study on the progression types of cancer in patients with breast cancer undergoing eribulin chemotherapy and tumor microenvironment (2018)
  • Author(s): Kashiwagi S, Tsujio G, Asano Y, Goto W, Takada K, Takahashi K, Morisaki T, Fujita H, Takashima T, Tomita S, Ohsawa M, Hirakawa K, Ohira M.
  • Journal Title: Journal of translational Medicine Volume: 16 Issue: 1 Pages: 54-54
  • DOI: 10.1186/s12967-018-1443-5
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of the treatment response to pre-operative chemotherapy in breast cancer by the checkpoint protein expression (2018)
  • Author(s): Asano Y, Kashiwagi S, Goto W, Takada K, Takahashi K, Morisaki T, Fujita H, Takashima T, Tomita S, Ohsawa M, Hirakawa K, Ohira M.
  • Journal Title: Journal of translational Medicine Volume: 16 Issue: 1 Pages: 87-87
  • DOI: 10.1186/s12967-018-1458-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prediction of Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer by Subtype Using Tumor-infiltrating Lymphocytes (2018)
  • Author(s): Asano Y, Kashiwagi S, Goto W, Takada K, Takahashi K, Hatano T, Takashima T, Tomita S, Motomura H, Ohsawa M, Hirakawa K, Ohira M.
  • Journal Title: Anticancer Research Volume: 38 Issue: 4 Pages: 2311-2321
  • DOI: 10.21873/anticanres.12476
  • Peer Reviewed / Open Access
• [Journal Article] Predictive value of improvement in the immune tumour microenvironment in patients with breast cancer treated with neoadjuvant chemotherapy (2018)
  • Author(s): Goto Wataru、Kashiwagi Shinichiro、Asano Yuka、Takada Koji、Takahashi Katsuyuki、Hatano Takaharu、Takashima Tsutomu、Tomita Shuhei、Motomura Hisashi、Ohsawa Masahiko、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: ESMO Open Volume: 3 Issue: 6 Pages: e000305-e000305
  • DOI: 10.1136/esmoopen-2017-000305
  • Peer Reviewed / Open Access
• [Journal Article] Significance of intrinsic breast cancer subtypes on the long-term prognosis after neoadjuvant chemotherapy (2018)
  • Author(s): Goto Wataru、Kashiwagi Shinichiro、Takada Koji、Asano Yuka、Takahashi Katsuyuki、Fujita Hisakazu、Takashima Tsutomu、Tomita Shuhei、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: Journal of Translational Medicine Volume: 16 Issue: 1 Pages: 307-307
  • DOI: 10.1186/s12967-018-1679-0
  • Peer Reviewed / Open Access
• [Journal Article] Significance of re-biopsy for recurrent breast cancer in the immune tumour microenvironment (2018)
  • Author(s): Takada Koji、Kashiwagi Shinichiro、Goto Wataru、Asano Yuka、Takahashi Katsuyuki、Hatano Takaharu、Takashima Tsutomu、Tomita Shuhei、Motomura Hisashi、Ohsawa Masahiko、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: British Journal of Cancer Volume: 119 Issue: 5 Pages: 572-579
  • DOI: 10.1038/s41416-018-0197-4
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of the treatment response to neoadjuvant chemotherapy in breast cancer by subtypes using tumor-infiltrating lymphocytes (2017)
  • Author(s): Asano Y, Kashiwagi S, Goto W, Takada K, Takahashi K, Hatano T, Takashima T, Tomita S, Motomura H, Ohsawa M, Hirakawa K, Ohira M.
  • Journal Title: Anticancer Research Volume: 38 Pages: 2311-2321
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of survival after neoadjuvant chemotherapy for breast cancer by evaluation of tumor-infiltrating lymphocytes and residual cancer burden (2017)
  • Author(s): Asano Yuka、Kashiwagi Shinichiro、Goto Wataru、Takada Koji、Takahashi Katsuyuki、Hatano Takaharu、Noda Satoru、Takashima Tsutomu、Onoda Naoyoshi、Tomita Shuhei、Motomura Hisashi、Ohsawa Masahiko、Hirakawa Kosei、Ohira Masaichi
  • Journal Title: BMC Cancer Volume: 17 Issue: 1 Pages: 888-888
  • DOI: 10.1186/s12885-017-3927-8
  • Peer Reviewed / Open Access
• [Journal Article] Expression and clinical significance of androgen receptor in triple-negative breast cancer. (2017)
  • Author(s): Asano Y, Kashiwagi S, Goto W, Takada K, Tanaka S, Morisaki T, Takashima T, Noda S, Onoda N, Ohsawa M, Hirakawa K, Ohira M.
  • Journal Title: Cancers Volume: 9 Issue: 1 Pages: 4-4
  • DOI: 10.3390/cancers9010004
  • NAID: 130005161483
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] メタボロミクスから捉えたアンドロン受容体陽性トリプルネガティブ乳癌における代謝調整機構の解明 (2019)
  • Author(s): 浅野有香, 柏木伸一郎, 高田晃次, 後藤 航, 森崎珠実, 野田 諭, 高島 勉, 小野田尚佳, 平川弘聖, 大平雅一
  • Organizer: 第119回 日本外科学会定期学術集会
• [Presentation] 腫瘍微小環境における線維化巣内浸潤リンパ球 (FF-TILs) による乳癌術前化学療法後の予後予測モデル (2018)
  • Author(s): 浅野有香, 柏木伸一郎, 後藤 航, 高田晃次, 森崎珠実, 野田 諭, 高島 勉, 小野田尚佳, 大澤政彦, 平川弘聖, 大平雅一
  • Organizer: 第118回 日本外科学会学術集会