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Clinical Pharmacology and Toxicology Research

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Can γH2AX assay be an endpoint in drug discovery?

Author(s): M. H. Yashavarddhan, Sandeep Kumar Shukla* and Ajay Kumar Sharma

Biomarker development is essential in the drug discovery field for effectiveness, toxicity, and optimization of doses when a drug is translated during pre-clinical to clinical trials. The present review highlights the prospective application of the γH2AX assay for pharmacological and toxicological evaluation in drug development. γH2AX is a phosphorylated form of H2AX protein belongs to the family H2A and is a well-known biomarker for measurement of DNA double strand breaks (DSBs). During chemotherapy, cancer cells are targeted by drugs that induce DSBs thereby result in cell death. In such scenario, γH2AX could be an informative marker for the effectiveness of the chemotherapeutic drug as wells as its associated toxicity in surrounding normal cells. Moreover, the canonical calculation of dose conversion of a drug from pre-clinical animal models to clinical trials in humans or non-human primates may not be effective all the time. The γH2AX assay may be used as one of possible marker for such dose conversion for any drug capable to generate DSBs. Besides, it can also be used as an effective biomarker in radiation countermeasures and bio-dosimeter which has been substantiated in many research articles. Considering the importance of γH2AX in various fields, this biomarker could be helpful in safety and efficacy assessment of new drugs.

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