Development of novel personalized drug therapy based on elucidation of drug sensitivity and resistance mechanism in bone and soft tissue tumors

2018 Fiscal Year Final Research Report

• Project/Area Number: 26713046
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kyushu University (2014, 2017-2018); National Cancer Center Japan (2015-2016)
• Principal Investigator: Endo Makoto 九州大学, 大学病院, 助教 (40713433)
• Project Period (FY): 2014-04-01 – 2019-03-31
• Keywords: 肉腫

Outline of Final Research Achievements

We developed sarcoma cell lines showing resistance to anticancer drugs such as doxorubicin, pazopanib and eribulin, which were widely used for bone and soft tissue sarcomas. The established drug resistant cell lines were used to analyze genes and proteins involved in drug resistance. Among them, the research using the pazopanib-resistant cell line of synovial sarcoma has succeeded in elucidating the mechanism of drug resistance and published in an English journal. In addition, we have found that HIF1α, a hypoxia-inducible factor involved in drug resistance, is a poor prognostic factor in malignant peripheral nerve sheath tumors and can be a therapeutic target. In leiomyosarcoma, we found that acquisition of drug resistance to eribulin involves overexpression of Class III β-tubulin and published in an English journal.

Free Research Field

骨軟部腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究成果を発展させ、臨床的な有用性が示されれば、骨軟部肉腫患者の薬物療法において、より効果を期待できる薬剤選択に有用と考えられる。また、本研究で明らかとなった薬物耐性獲得機序を阻害することに成功すれば、薬物療法の効果を長期に持続させることが可能となり、骨軟部肉腫患者の予後改善につながる可能性がある。