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Updated: May 6, 2026

An Automated Microscopic Scoring Method for the γ-H2AX Foci Assay in Human Peripheral Blood Lymphocytes
Published on: December 25, 2021
Can γH2AX be used to personalise cancer treatment?
K Shah1, B Cornelissen, A E Kiltie
1University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK. katherine.vallis@oncology.ox.ac.uk.
Abstract:
Many cancer therapeutics, including radiation therapy, damage DNA eliciting the DNA damage response (DDR). Clinical assays that characterise the DDR could be used to personalise cancer treatment by indicating the extent of damage to tumour and normal tissues and the nature of the cellular response to that damage. The phosphorylated histone γH2AX is generated early in the response to DNA double-strand breaks, the most deleterious form of DNA damage. Translational researchers are developing tissue sampling and assay strategies to apply the measurement of γH2AX to a range of clinical questions, including that of tumour response. The presence of γH2AX is also associated with other cell states including replication stress, hypoxia and apoptosis, which could influence the relationship between γH2AX and clinical endpoints. This review aims to assess the potential of γH2AX as a practical and clinically useful biomarker of tumour and normal tissue responses to therapy.
Insights
The phosphorylated histone gamma-H2AX (γH2AX) biomarker shows promise for assessing DNA damage from cancer therapies. Measuring γH2AX could personalize treatment by evaluating tumor and normal tissue responses to therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cancer therapeutics like radiation therapy induce DNA damage, activating the DNA damage response (DDR).
- The phosphorylated histone γH2AX is an early marker of DNA double-strand breaks, a critical form of DNA damage.
- Current clinical assays for DDR aim to personalize cancer treatment by assessing damage extent and cellular response.
Purpose of the Study:
- To review the potential of γH2AX as a clinically useful biomarker for evaluating tumor and normal tissue responses to cancer therapy.
- To assess the clinical utility of measuring γH2AX in the context of DNA damage response.
Main Methods:
- Review of existing literature on γH2AX as a biomarker in cancer therapy.
- Analysis of translational research strategies for γH2AX measurement in clinical settings.
- Evaluation of the association between γH2AX and other cellular states (replication stress, hypoxia, apoptosis).
Main Results:
- γH2AX is rapidly generated following DNA double-strand breaks, indicating significant DNA damage.
- γH2AX measurement is being developed for clinical assays to assess treatment response.
- The presence of γH2AX can be influenced by other cellular conditions, potentially affecting its interpretation.
Conclusions:
- γH2AX holds significant potential as a practical biomarker for assessing tumor and normal tissue responses to cancer therapies.
- Further development of tissue sampling and assay strategies is needed to fully realize the clinical utility of γH2AX.
- Understanding the influence of confounding cellular states on γH2AX is crucial for accurate clinical application.
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