ID | 48258 |
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著者 |
Kuroda, Shinji
Department of Gastroenterological Surgery, Okayama University Graduate School for Medicine, Dentistry and Pharmaceutical Sciences
Urata, Yasuo
Oncolys BioPharma Inc.
Fujiwara, Toshiyoshi
Department of Gastroenterological Surgery, Okayama University Graduate School for Medicine, Dentistry and Pharmaceutical Sciences
ORCID
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抄録 | Radiotherapy plays a central part in cancer treatment, and use of radiosensitizing agents can greatly enhance this modality. Although studies have shown that several chemotherapeutic agents have the potential to increase the radiosensitivity of tumor cells, investigators have also studied a number of molecularly targeted agents as radiosensitizers in clinical trials based on reasonably promising preclinical
data. Recent intense research into the DNA damage-signaling pathway revealed that ataxia-telangiectasia mutated (ATM) and the Mre11-Rad50-NBS1 (MRN) complex play central roles in DNA repair and cell cycle checkpoints and that these molecules are promising targets for radiosensitization. Researchers recently developed three ATM inhibitors (KU-55933, CGK733, and CP466722) and an MRN complex inhibitor (mirin) and showed that they have great potential as radiosensitizers of tumors in preclinical studies. Additionally, we showed that a telomerase-dependent oncolytic adenovirus that we developed (OBP-301 [telomelysin]) produces profound radiosensitizing effects by inhibiting the MRN complex via the adenoviral E1B55kDa protein. A recent Phase I trial in the United States determined that telomelysin was safe and well tolerated in humans, and this agent is about to be tested in combination
with radiotherapy in a clinical trial based on intriguing preclinical data demonstrating that telomelysin and ionizing radiation can potentiate each other. In this review, we highlight the great potential of ATM and MRN complex inhibitors, including telomelysin, as radiosensitizing agents.
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キーワード | ATM (ataxia-telangiectasia mutated)
MRN (Mre11-Rad50-NBS1) complex
radiosensitization
adenovirus
E1B55kDa
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Amo Type | Review
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出版物タイトル |
Acta Medica Okayama
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発行日 | 2012-04
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巻 | 66巻
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号 | 2号
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出版者 | Okayama University Medical School
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開始ページ | 83
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終了ページ | 92
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ISSN | 0386-300X
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NCID | AA00508441
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資料タイプ |
学術雑誌論文
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言語 |
英語
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著作権者 | CopyrightⒸ 2012 by Okayama University Medical School
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論文のバージョン | publisher
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査読 |
有り
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Web of Science KeyUT |