The article discusses the role of histone H2AX phosphorylation, specifically γH2AX, in detecting DNA double-strand breaks (DSBs) and its implications for cancer. γH2AX is a sensitive marker for DSBs, which can lead to genomic instability and cancer. However, paradoxically, DSBs are also used as a therapeutic strategy to kill cancer cells. The detection of γH2AX foci can help in detecting precancerous cells, staging cancers, monitoring treatment effectiveness, and developing new anticancer drugs. The article also explores the sources of DSBs, including direct attacks on DNA, reactive oxygen species (ROS), metabolic processes, deficient repair, telomere erosion, and programmed biological processes. It highlights the clinical and therapeutic applications of γH2AX, such as diagnostic tools for detecting precancerous lesions and assessing treatment responses. Additionally, the article discusses the potential of γH2AX as a biomarker in drug development and phase 0 protocols to tailor treatments to individual patients.The article discusses the role of histone H2AX phosphorylation, specifically γH2AX, in detecting DNA double-strand breaks (DSBs) and its implications for cancer. γH2AX is a sensitive marker for DSBs, which can lead to genomic instability and cancer. However, paradoxically, DSBs are also used as a therapeutic strategy to kill cancer cells. The detection of γH2AX foci can help in detecting precancerous cells, staging cancers, monitoring treatment effectiveness, and developing new anticancer drugs. The article also explores the sources of DSBs, including direct attacks on DNA, reactive oxygen species (ROS), metabolic processes, deficient repair, telomere erosion, and programmed biological processes. It highlights the clinical and therapeutic applications of γH2AX, such as diagnostic tools for detecting precancerous lesions and assessing treatment responses. Additionally, the article discusses the potential of γH2AX as a biomarker in drug development and phase 0 protocols to tailor treatments to individual patients.