Exploring γH2AX as a key biomarker for DNA Damage in cancer therapy.

Exploring γH2AX as a key biomarker for DNA Damage in cancer therapy.

Phosphorylation of H2AX at Serine 139 signals DNA double-strand breaks, resulting in the formation of γH2AX – an essential biomarker for DNA damage in cancer therapy. To date, it has been utilised in over 50 clinical trials, guiding the assessment of treatment efficacy and strategy.

While peripheral blood lymphocytes are commonly used for γH2AX studies, this spotlight explores why skin and hair biopsies may offer more relevant insights for solid tumour types.

• γH2AX is a key biomarker in clinical trials, crucial for assessing DNA damage in cancer therapies. Its detection of DNA double-strand breaks (DSBs) provides vital insights into treatment efficacy, guiding personalised treatment strategies.
• Blood is the most commonly used biomarker source for detecting γH2AX in clinical trials. However, it may not accurately represent tissues of epithelial origin, such as solid tumours, as it fails to reflect the tumour’s biological environment and therapy response.
• Skin – of epithelial origin – offer an effective alternative for detecting γH2AX in solid tumours. Used in clinical trials for several cancer types, immunofluorescence methods visualise γH2AX foci, providing vital insights into tumour responses to treatment
• Although skin biopsies can be invasive, hair provides a less invasive alternative for measuring γH2AX in clinical settings. Studies demonstrate that plucked hair follicles effectively assess DNA damage and monitor treatment responses in both preclinical and clinical trials.
• Studies using eyebrow hair have successfully detected γH2AX induction after treatment in solid tumours. However, the short anagen phase of eyebrow hair limits its effectiveness, highlighting the need for better detection methods to improve biomarker analysis.
• Plucked scalp hair, abundant in anagen-phase follicles, is ideal for assessing γH2AX. This approach is valuable in oncology for evaluating cell proliferation and cell death, and it can also be used in conditions like alopecia, providing insights into cellular responses.
• At Epistem, we employ human hair for ex vivo, proof-of-concept studies that allow rapid assessment of biomarker expression and modulation post treatment.
• See below an image highlighting γH2AX induction after Epirubicin treatment.

• Watch our recent webinar to learn more about Epistem’s clinical and preclinical ex-vivo plucked hair platform to detect γH2AX and other disease-relevant targets. (Link to webinar page).
• Book your free consultation. Get in touch to discuss your next hair biomarker study at Epistem. (Link to Contact us page).