Cellular Stress Responses in Radiotherapy

Abstract

Radiotherapy is one of the major cancer treatment strategies. Exposure to penetrating radiation causes cellular stress, directly or indirectly, due to the generation of reactive oxygen species, DNA damage, and subcellular organelle damage and autophagy. These radiation-induced damage responses cooperatively contribute to cancer cell death, but paradoxically, radiotherapy also causes the activation of damage-repair and survival signaling to alleviate radiation-induced cytotoxic effects in a small percentage of cancer cells, and these activations are responsible for tumor radio-resistance. The present study describes the molecular mechanisms responsible for radiation-induced cellular stress response and radioresistance, and the therapeutic approaches used to overcome radioresistance.

Enhanced Expression of IGFBP-3 Reduces Radiosensitivity and Is Associated with Poor Prognosis in Oral Squamous Cell Carcinoma

“…Second, although radiation-induced DSBs are repaired by two major pathways, namely NHEJ and HR, our analysis focused on the relationship between IGFBP-3 and the NHEJ protein DNA-PKcs. Finally, other mechanisms are involved in radioresistance, not only DNA repair, including several stress-responsive signalling pathways such as reactive oxygen species generation and activation of cytoprotective autophagy [37]. Therefore, further studies are required to confirm the effects of a combination therapy of IGFBP-3-targeting drugs and radiotherapy on in vivo models and to assess the relationship between IGFBP-3 and the HR DNA repair pathway, as well as other stress-responsive signalling pathways, in radioresistance.…”

The Role of α1-Microglobulin (A1M) in Erythropoiesis and Erythrocyte Homeostasis—Therapeutic Opportunities in Hemolytic Conditions

“…Radiation is well known to generate the production of ROS [ 46 ] and has been shown to cause damage to both directly irradiated cells and non-irradiated bystander cells [ 47 ]. Therefore, by reducing oxidative stress, A1M has been suggested to be a potential radioprotector.…”

Overcoming radiation resistance by iron-platinum metal alloy nanoparticles in human copper transport 1-overexpressing cancer cells via mitochondrial targeting

“…Likewise, exposure to ionizing radiation also causes abundant cell stress directly or indirectly, due to the generation of ROS in mitochondria [32]. Excessive levels of ROS can alter mitochondrial membrane permeability to disrupt the electron transport chain and cause imbalance of the intracellular redox system [33][34][35]. Therefore, combination of NPs with ionizing radiation triggering ROS burst that leads to mitochondrial dysfunction may be an effective approach for cancer treatment using FePt NPs/radiation strategy [36,37].…”