Radiation-induced DNA damage enhancement

Radiation-induced DNA damage enhancement refers to strategies that increase the lethality of IR by either amplifying DNA lesions—especially double-strand breaks—or by suppressing cellular DNA damage responses and repair pathways such as homologous recombination and non-homologous end joining, thereby promoting apoptosis, checkpoint failure, and replication catastrophe in cancer cells. It is operationalized via radiosensitizing agents, including checkpoint inhibitors, signaling pathway inhibitors (e.g., MEK1/2 inhibitors), and DNA-interacting drugs (e.g., camptothecin derivatives), with effects often assessed by persistent γH2AX foci as a DSB biomarker. While effective for overcoming radioresistance in cancer, these approaches must balance increased tumor kill with the risk of normal tissue toxicity.

Other names

Radiation-induced DNA damage sensitizationRadiosensitization (by enhancing DNA damage)Enhancement of IR-induced DNA double-strand breaks

Inhibition of HR and/or NHEJ DNA double-strand break repair after IR, leading to persistent DSBs and enhanced cell killing. Checkpoint inhibition to both inhibit repair and increase replication stress during/after IR. Increasing formation of DSBs or preventing their resolution, monitored by γH2AX foci persistence.