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Strategies To Assess Hypoxic/HIF-1-Active Cancer Cells for the Development of Innovative Radiation Therapy
Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
* Author to whom correspondence should be addressed.
Received: 4 August 2011; in revised form: 12 August 2011 / Accepted: 9 September 2011 / Published: 15 September 2011
Abstract: Local tumor recurrence and distant tumor metastasis frequently occur after radiation therapy and result in the death of cancer patients. These problems are caused, at least in part, by a tumor-specific oxygen-poor microenvironment, hypoxia. Oxygen-deprivation is known to inhibit the chemical ionization of both intracellular macro-molecules and water, etc., and thus reduce the cytotoxic effects of radiation. Moreover, DNA damage produced by free radicals is known to be more repairable under hypoxia than normoxia. Hypoxia is also known to induce biological tumor radioresistance through the activation of a transcription factor, hypoxia-inducible factor 1 (HIF-1). Several potential strategies have been devised in radiation therapy to overcome these problems; however, they have not yet achieved a complete remission. It is essential to reveal the intratumoral localization and dynamics of hypoxic/HIF-1-active tumor cells during tumor growth and after radiation therapy, then exploit the information to develop innovative therapeutic strategies, and finally damage radioresistant cells. In this review, we overview problems caused by hypoxia/HIF-1-active cells in radiation therapy for cancer and introduce strategies to assess intratumoral hypoxia/HIF-1 activity.
Keywords: radiation therapy; tumor hypoxia; radioresistance; hypoxia-inducible factor 1 (HIF-1); molecular imaging
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Yeom, C.J.; Zeng, L.; Zhu, Y.; Hiraoka, M.; Harada, H. Strategies To Assess Hypoxic/HIF-1-Active Cancer Cells for the Development of Innovative Radiation Therapy. Cancers 2011, 3, 3610-3631.
Yeom CJ, Zeng L, Zhu Y, Hiraoka M, Harada H. Strategies To Assess Hypoxic/HIF-1-Active Cancer Cells for the Development of Innovative Radiation Therapy. Cancers. 2011; 3(3):3610-3631.
Yeom, Chan Joo; Zeng, Lihua; Zhu, Yuxi; Hiraoka, Masahiro; Harada, Hiroshi. 2011. "Strategies To Assess Hypoxic/HIF-1-Active Cancer Cells for the Development of Innovative Radiation Therapy." Cancers 3, no. 3: 3610-3631.