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Cancers 2017, 9(11), 147; doi:10.3390/cancers9110147

Clinical and Functional Assays of Radiosensitivity and Radiation-Induced Second Cancer

1
Cancer Research Division, Peter MacCallum Cancer Centre, 305 Grattan Street, Parkville, VIC 3000, Australia
2
Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia
3
Physical Sciences, Peter MacCallum Cancer Centre, 305 Grattan Street, Parkville, VIC 3000, Australia
4
Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, 305 Grattan Street, Parkville, VIC 3000, Australia
5
The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia
*
Author to whom correspondence should be addressed.
Received: 22 September 2017 / Revised: 24 October 2017 / Accepted: 24 October 2017 / Published: 27 October 2017
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis)
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Abstract

Whilst the near instantaneous physical interaction of radiation energy with living cells leaves little opportunity for inter-individual variation in the initial yield of DNA damage, all the downstream processes in how damage is recognized, repaired or resolved and therefore the ultimate fate of cells can vary across the population. In the clinic, this variability is observed most readily as rare extreme sensitivity to radiotherapy with acute and late tissue toxic reactions. Though some radiosensitivity can be anticipated in individuals with known genetic predispositions manifest through recognizable phenotypes and clinical presentations, others exhibit unexpected radiosensitivity which nevertheless has an underlying genetic cause. Currently, functional assays for cellular radiosensitivity represent a strategy to identify patients with potential radiosensitivity before radiotherapy begins, without needing to discover or evaluate the impact of the precise genetic determinants. Yet, some of the genes responsible for extreme radiosensitivity would also be expected to confer susceptibility to radiation-induced cancer, which can be considered another late adverse event associated with radiotherapy. Here, the utility of functional assays of radiosensitivity for identifying individuals susceptible to radiotherapy-induced second cancer is discussed, considering both the common mechanisms and important differences between stochastic radiation carcinogenesis and the range of deterministic acute and late toxic effects of radiotherapy. View Full-Text
Keywords: radiosensitivity; second cancer; radiotherapy; radiogenomics; functional assay radiosensitivity; second cancer; radiotherapy; radiogenomics; functional assay
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Habash, M.; Bohorquez, L.C.; Kyriakou, E.; Kron, T.; Martin, O.A.; Blyth, B.J. Clinical and Functional Assays of Radiosensitivity and Radiation-Induced Second Cancer. Cancers 2017, 9, 147.

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