2023 Fiscal Year Final Research Report
Investigation of the Mechanisms of Malignant Transformation in Chondrosarcoma and Search for Novel Therapeutic Targets
| Project/Area Number |
21K20838
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0901:Oncology and related fields
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2021-08-30 – 2024-03-31
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| Keywords | 軟骨肉腫 / エピゲノム / DNAメチル化 / がん治療 |
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| Outline of Final Research Achievements |
Dedifferentiated chondrosarcoma (DDCS) is highly resistant to chemotherapy and radiation therapy, and has a poor prognosis, making the development of new treatments highly desirable. In this study, we focused on epigenomic abnormalities in DDCS to identify new therapeutic targets. Through comprehensive genetic analysis, we focused on a factor called PRKCZ. Clinical samples of DDCS, as well as in vitro and in vivo experiments, revealed that increased DNA methylation and decreased PRKCZ expression in DDCS inhibit apoptosis through the inactivation of the ATM/CHK2 pathway. Administration of decitabine was shown to induce apoptosis and inhibit cell proliferation, suggesting that PRKCZ could be a novel therapeutic target for DDCS.
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| Free Research Field |
骨軟部腫瘍
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| Academic Significance and Societal Importance of the Research Achievements |
脱分化型軟骨肉腫（DDCS）は予後不良な腫瘍であるため新規治療法の開発が望まれている。今回我々はDDCSにおいてDNAメチル化の増加とPRKCZの発現低下はATM/CHK2経路の不活性化を介してアポトーシスを阻害するという新しいメカニズムを解明した。その経路をデシタビンの投与により阻害すると、アポトーシスを誘導して細胞増殖を抑制することが示された。
本研究により軟骨肉腫に対する新しい治療ターゲットが解明された。また、デシタビンは既存薬であるため早期の臨床応用が期待でき、DDCS患者の生存率向上と生活の質の改善に寄与する可能性がある。
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