Ionizing radiation-induced DNA damage response pathway

Ionizing radiation-induced DNA damage response pathways encompass the cellular mechanisms activated in tumor cells after exposure to ionizing radiation, primarily used in cancer therapy. Radiation produces various types of DNA lesions, and the most lethal are double-strand breaks (DSBs). Cells recognize DNA damage through sensor proteins (ATM, ATR, DNA-PKcs), which initiate signaling cascades, checkpoint activation (G1, S, G2/M), and trigger repair by homologous recombination (HR), non-homologous end joining (NHEJ), or base excision repair (BER). Failure to repair DNA causes cell death, which is the desired outcome for tumor cells in radiotherapy. Drugs that inhibit specific components of these pathways—such as PARP inhibitors, ATM/ATR inhibitors, and WEE1 inhibitors—increase tumor cell sensitivity to radiation. Accurate targeting of these responses remains challenging, as normal cell toxicity and repair compensation can limit efficacy.

Other names

DNA damage response (DDR) pathwayDNA repair pathwayIR-induced DDRRadiation-induced DDR

Inhibit DNA damage repair pathways to increase radiosensitivity. Block cell cycle checkpoints to induce mitotic catastrophe. Trap PARP on DNA to prevent single-strand break repair (PARP inhibitors).