2018 Fiscal Year Final Research Report
Local adjuvant therapy on bone and soft tissue sarcoma by combination of telomerase-specific oncolytic adenovirus with radiotherapy
| Project/Area Number |
16K10862
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
尾崎 敏文 岡山大学, 医歯薬学総合研究科, 教授 (40294459)
藤原 智洋 岡山大学, 医歯薬学総合研究科, 助教 (80639211)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 骨軟部腫瘍 / 肉腫 / 悪性腫瘍 / ウイルス治療 |
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| Outline of Final Research Achievements |
Our study demonstrated that OBP-702 has much stronger anti-tumor effect compared to OBP-301, and sensitizes radiotherapy to various types of osteosarcoma cell lines. We recently identified that OBP-702 induces profound apoptosis through p53-dependent BAX upregulation and E1A- dependent p21 and MDM2 downregulation in epithelial malignant cells. This study revealed further molecular mechanisms of synergistic antitumor effect of OBP-702 with radiation; p53-dependent apoptosis, downregulation of the anti-apoptotic BCL-2 family proteins and interruption of the cellular DNA repair mechanism. Currently, a Phase I/II clinical study of OBP-301 in combination with radiation against esophageal cancer patients is underway in Japan, and preclinically OBP-702 provides more profound therapeutic potentials than OBP-301 in various tumors. Thus, OBP-702 would provide a novel treatment strategy for STS and wide application of radiotherapy for localized as well as advanced musculoskeletal sarcoma.
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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 |
テロメラーゼ活性依存性に癌細胞内で増殖して細胞死を誘導する腫瘍選択的融解ウイルスは当大学で開発され、食道癌ですでに臨床試験が開始されている。今年度までに行った基礎研究から、これらのウイルス治療は単独で投与するよりも、放射線治療や化学療法と併用することで、より強力な抗腫瘍効果を認めた。さらに、相乗効果も確認でき、肉腫に対する新規療法となりうる。そこで、これらのウイルス治療を利用した実際の臨床応用では、単独投与ではなく、放射線治療との併用療法を行うことで、肉腫を安全に切除することが可能となる。また、正常組織を安全に温存できれば、術後の機能が改善され、患者のQOL向上につながる。
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