Target intelligence / Profile preview

DNA Damage Induced by Ionizing Radiation (IR-DNA Damage)

Target
IR-DNA Damage
Molecular classification
DNA, Genomic Instability, DNA Damage Response (DDR)
01

Overview

Ionizing radiation is a cancer therapy that targets tumor cells by inducing DNA damage, primarily double-strand breaks (DSBs). The damage arises from direct interaction of radiation with DNA or indirectly via reactive oxygen species (ROS) generated by the radiation. Cells respond via the DNA Damage Response (DDR), leading to cell cycle arrest, repair, apoptosis, or senescence. Surviving cells can exhibit genomic instability. Radiation induces immunogenic cell death. Therapeutic strategies involve radiosensitizers that inhibit DDR components to enhance tumor kill. Safety concerns include damage to normal tissues and secondary malignancies.

Other names
Radiation-induced DNA damageIonizing radiation-induced DNA lesionsDNA strand breaks from irradiation
02

Mechanism of action

Ionizing radiation induces DNA damage primarily through the generation of double-strand breaks (DSBs), single-strand breaks (SSBs), base modifications, and DNA crosslinks via direct bond cleavage and indirect action through reactive oxygen species (ROS). This activates the DNA Damage Response (DDR) pathways, leading to cell cycle arrest, DNA repair, and ultimately, apoptosis, mitotic catastrophe, senescence, or genomic instability if repair fails. The immunogenic cell death pathway is also activated to promote immune recognition and clearance of damaged tumor cells.

03

Biological functions

Cell deathApoptosisCell cycle arrestDNA repairGenomic instabilityImmune response
04

Disease associations

CancerSecondary malignancies
05

Safety considerations

Secondary malignanciesDamage to normal tissuesGenomic instabilityOff-target effects of radiosensitizers
06

Interacting drugs

ATM inhibitors

4 more in the full profile.

07

Biomarkers

p53 statusATM/ATR kinase expressionPARP expressioncGAS-STING pathway activationType I interferon levels

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