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Efficient Protocol for the Identification of Hypoxic Cell Radiosensitisers

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Book cover Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 899))

Abstract

An evolution in radiotherapy practice is leading to greater use of stereotactic body radiotherapy (SBRT), raising the prospect of increased hypoxic cell radioresistance. New clinical interest in nitroimidazole radiosensitisers, combined with appropriate biomarkers, signals a revival for radiosensitisers in the context of SBRT. Our interest in modifiers of radiation therapy led us to revisit this area and we have identified a new class of nitroimidazole radiosensitiser. We have developed an abbreviated screening protocol suitable for an academic drug discovery laboratory which allows expeditious triage of compounds with poor physicochemical and in vitro properties and combines in vitro radiosensitisation data with tumour pharmacokinetic data to efficiently select candidates for further evaluation.

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Acknowledgements

The authors would like to thank Dr Thorsten Melcher (J&J Innovation) and Professor Bill Wilson for helpful discussions and thank Dr Adrian Blaser, Ms Karen Tan and Mr Sisira Kumara for technical assistance. The authors acknowledge support from the University of Auckland’s Biopharma Thematic Research Initiative, UniServices Investment/Ministry of Business, Innovation and Employment Pre-Seed Accelerator Fund and the Cancer Society of New Zealand.

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Authors and Affiliations

  1. Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    Cho Rong Hong, Jingli Wang Ph.D., Kevin O. Hicks Ph.D. & Michael P. Hay Ph.D.

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  1. Cho Rong Hong
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  2. Jingli Wang Ph.D.
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  3. Kevin O. Hicks Ph.D.
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  4. Michael P. Hay Ph.D.
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Correspondence to Michael P. Hay Ph.D. .

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Editors and Affiliations

  1. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Constantinos Koumenis

  2. Cell & Developmental Biology, Oregon Health & Science University, Portland, Oregon, USA

    Lisa M. Coussens

  3. Department of Radiation Oncology, Stanford University School of Medic, Stanford, California, USA

    Amato Giaccia

  4. Department of Oncology, University of Oxford, Oxford, Oxfordshire, United Kingdom

    Ester Hammond

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Hong, C.R., Wang, J., Hicks, K.O., Hay, M.P. (2016). Efficient Protocol for the Identification of Hypoxic Cell Radiosensitisers. In: Koumenis, C., Coussens, L., Giaccia, A., Hammond, E. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 899. Springer, Cham. https://doi.org/10.1007/978-3-319-26666-4_16

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