Development of the treatment of drug resistance of soft tissue sarcoma by precision medicine

• Project/Area Number: 18K09067
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kyushu University
• Principal Investigator: Matsumoto Yoshihiro 九州大学, 医学研究院, 准教授 (10346794)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Precision medicine / 骨軟部腫瘍 / 末梢血免疫関連マーカー / エリブリン / 分子標的治療 / 薬剤耐性 / 軟部肉腫 / バイオマーカー

Outline of Final Research Achievements

The resistance of malignant bone and soft tissue tumors, especially soft tissue sarcomas, to anti-tumor drugs is a major problem. In this project, we studied the biological characteristics of malignant bone and soft tissue tumors, and obtained research results on the basis of Precision Medicine, especially from the viewpoint of drug resistance, focusing on the following three points. (1) The efficacy of eribulin (Eri), a typical treatment for soft tissue sarcoma, can be predicted using peripheral blood immune-related markers. (2) Expression of Beta-tublin3 is a biomarker of drug resistance in Eri. (3) In giant cell tumor of bone, it is possible to predict osteosclerosis after anti-RANKL antibody administration by evaluating the nuclear translation of beta-catenin.

Academic Significance and Societal Importance of the Research Achievements

本研究により、軟部腫瘍を中心とした悪性骨軟部腫瘍の生物学的特性に関する研究が進んだ。上述の成果により、使用可能な限られたリソース(薬剤)を適切に選択する根拠が明らかとなった。即ち、薬剤投与前に適切に検査を行うことにより、薬剤の治療効果、ひいては各々の症例の予後を改善させることが可能になると思われた。

Research Products

• [Journal Article] PD-L1 and IDO-1 expression in undifferentiated pleomorphic sarcoma: The associations with tumor infiltrating lymphocytes, dMMR and HLA class I. (2021)
  • Author(s): Ishihara S, Yamada Y, Iwasaki T, Yoshimoto M, Toda Y, Kohashi K, Yamamoto H, Matsumoto Y, Nakashima Y, Oda Y.
  • Journal Title: Oncol Rep. Volume: 45 Issue: 1 Pages: 379-389
  • DOI: 10.3892/or.2020.7837
  • Peer Reviewed
• [Journal Article] Immunotherapy for osteosarcoma. (2020)
  • Author(s): Yahiro K, Matsumoto Y.
  • Journal Title: Hum Vaccin Immunother. Volume: N/A Issue: 5 Pages: 1-2
  • DOI: 10.1080/21645515.2020.1824499
  • Peer Reviewed
• [Journal Article] Eribulin as a first-line treatment for soft tissue sarcoma patients with contraindications for doxorubicin (2020)
  • Author(s): Tsuchihashi K, Kusaba H, Yoshihiro T, Fujiwara T, Setsu N, Endo M, Matsumoto Y, Imajima T, Shinohara Y, Ito M, Yamaga S, Tanoue K, Arimizu K, Ohmura H, Hanamura F, Yamaguchi K, Isobe T, Ariyama H, Nakashima Y, Akashi K, Baba E.
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 20896-20896
  • DOI: 10.1038/s41598-020-77898-y
  • Peer Reviewed / Open Access
• [Journal Article] PD-L1 and IDO1 expression and tumor-infiltrating lymphocytes in osteosarcoma patients: comparative study of primary and metastatic lesions (2020)
  • Author(s): Toda Y, Kohashi K, Yamada Y, Yoshimoto M, Ishihara S, Ito Y, Iwasaki T, Yamamoto H, Matsumoto Y, Nakashima Y, Mawatari M, Oda Y.
  • Journal Title: J Cancer Res Clin Oncol. Volume: 146 Issue: 10 Pages: 2607-2620
  • DOI: 10.1007/s00432-020-03242-6
  • Peer Reviewed
• [Journal Article] Activation of TLR4 Signaling Inhibits Progression of Osteosarcoma by Stimulating CD8-positive Cytotoxic Lymphocytes. (2020)
  • Author(s): Yahiro K, Matsumoto Y, Yamada H, Endo M, Setsu N, Fujiwara T, Nakagawa M, Kimura M, Shimada E, Okada S, Oda Y, Nakashima Y.
  • Journal Title: Cancer Immunol Immunother Volume: - Issue: 5 Pages: 745-758
  • DOI: 10.1007/s00262-020-02508-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical results of carbon-ion radiotherapy with separation surgery for primary spine/paraspinal sarcomas. (2019)
  • Author(s): Matsumoto Y, Matsunobu A, Kawaguchi K, Hayashida M, Iida K, Saiwai H, Okada S, Endo M, Setsu N, Fujiwara T, Baba S, Nomoto S, Nakashima Y.
  • Journal Title: Int J Clin Oncol Volume: 24 Issue: 11 Pages: 1490-1497
  • DOI: 10.1007/s10147-019-01505-y
  • Peer Reviewed
• [Journal Article] Diagnostic utility of histone H3.3 G34W, G34R, and G34V mutant-specific antibodies for giant cell tumors of bone (2018)
  • Author(s): Yamamoto Hidetaka、Iwasaki Takeshi、Yamada Yuichi、Matsumoto Yoshihiro、Otsuka Hiroshi、Yoshimoto Masato、Kohashi Kenichi、Taguchi Kenichi、Yokoyama Ryohei、Nakashima Yasuharu、Oda Yoshinao
  • Journal Title: Human Pathology Volume: 73 Pages: 41-50
  • DOI: 10.1016/j.humpath.2017.11.020
  • Peer Reviewed
• [Journal Article] Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line. (2018)
  • Author(s): Yahiro K, Matsumoto Y, Fukushi JI, Kawaguchi KI, Endo M, Setsu N, IIda K, Fukushima S, Nakagawa M, Kimura A, Oda Y, Nakashima Y
  • Journal Title: Anal Cell Pathol Volume: なし Pages: 8987568-8987568
  • DOI: 10.1155/2018/8987568
  • Peer Reviewed / Open Access
• [Journal Article] Cancer-testis antigens are predominantly expressed in uterine leiomyosarcoma compared with non?uterine leiomyosarcoma (2017)
  • Author(s): Iura Kunio、Kohashi Kenichi、Yasutake Nobuko、Ishii Takeaki、Maekawa Akira、Bekki Hirofumi、Otsuka Hiroshi、Yamada Yuichi、Yamamoto Hidetaka、Ohishi Yoshihiro、Matsumoto Yoshihiro、Iwamoto Yukihide、Oda Yoshinao
  • Journal Title: Oncology Letters Volume: 15 Pages: 441-446
  • DOI: 10.3892/ol.2017.7274
  • Peer Reviewed
• [Presentation] 軟部肉腫に対する新規薬物療法 (2018)
  • Author(s): 松本 嘉寛
  • Organizer: 第51回日本整形外科学会骨軟部腫瘍学術集会
  • Invited