Purpose: Peggy Olive of the BC cancer research center (BCCRC), Vancouver, Canada, dedicated her career to improving the efficiency of radiation in the treatment of cancer. Keenly interested in the study of hypoxic cell radiosensitizers, she recognized the importance of DNA repair in improving the efficacy of radiotherapy. At the BCCRC she developed two methods for clinical practice that detect and quantitate DNA damage in mammalian cells. The alkaline comet assay and phosphorylated gamma histone H2AX (γH2AX) protein foci staining were two sensitive and attractive techniques that she attempted to apply in clinical practice.
Conclusion: Peggy Olive was able to establish the comet and the γH2AX assays as prospective predictive biomarkers in the application of personalized radiation treatment and improved cancer treatment outcomes. Nevertheless, several studies with a large number of samples are required before application of these biomarkers in routine radiotherapy could become a reality. The advent of 'omis' and microchip technologies envisage successful outcomes of future research in this direction.
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Retention of γH2AX foci as an indication of lethal DNA damage.
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The application of biological responses of tumours to predict clinical responses to treatment represents a challenging goal with the potential to inform treatment decisions and improve outcome. If tumour cell death is the result of the inability of a cell to repair complex DNA damage, and if γH2AX foci mark sites of unrepaired double-strand breaks, then it may be possible to use residual γH2AX foci to identify treatment-resistant tumour cells early in the course of therapy. This review will highlight some of the evidence that supports the idea that residual γH2AX foci, within certain limitations, may be useful as an early indicator of tumour response to radiotherapy in situ, either alone or in combination with chemotherapy.
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