Exploring the molecular mechanism of cancer radiosensitization: the impact of physical stimulation therapy

Radiotherapy for cancer is a local treatment method that uses radiation to treat tumors. It is one of the main approaches for treating malignant tumors. Radiotherapy uses ionizing radiation on living organisms to cause necrosis of tumor cells. However, the DNA damage repair mechanisms of tumor cells and the hypoxic microenvironment of tumors limit the effectiveness of radiotherapy. Tumor cells can also achieve radioresistance through a variety of signaling pathways. The radiation tolerance of adjacent tissues also directly affects the effect of radiotherapy. Stimulation of tumor cells through physical methods such as ultrasound, light, heat, electricity, and magnetic fields can not only improve the hypoxic microenvironment of tumors and directly damage DNA but can also solve the problem of radioresistance by regulating a variety of signaling molecules. Physical stimulation therapy has high specificity and targeted effects, making it widely used in radiosensitization applications. However, the molecular mechanisms underlying the radiosensitizing effects of physical stimulation therapy are not fully understood at a practical level. In this review, we summarize the signaling pathways related to radioresistance as well as the established and potential molecular mechanisms responsible for radiosensitization induced by physical stimulation to provide insights for future radiosensitivity studies on physical stimulation therapies.