Cancer is a group of diseases characterized by damage to cellular DNA and abnormal cell proliferation. One of the common and curative treatment modalities used in cancer therapy is radiotherapy, which represents a primary approach in cancer management. Radiotherapy aims to deliver a sufficient dose of radiation to destroy tumor cells (target tissue) while minimizing the damage to surrounding at-risk tissues. Understanding the effects of ionizing radiation on living tissues is crucial for justifying the principles of radioprotection for patients, the public, and healthcare professionals, and for developing new therapeutic strategies. A better understanding of the radiobiological mechanisms underlying the response to high-dose radiation therapy—known as the 5Rs—is essential to predict the short- and long-term effects on both the tumor and the surrounding healthy tissues, and thus to improve the therapeutic index.

The 5Rs of radiobiology can be summarized from a simplified perspective as: repair, repopulation, reoxygenation, redistribution (within the cell cycle), and radiosensitivity. This study aims to examine the 5Rs, which describe the cellular response to high-dose ionizing radiation used in radiation therapy, and to discuss their relationship with the cell cycle. Certain factors reduce the efficacy of radiation therapy, such as tumor cell repopulation and sublethal damage repair. Others enhance local tumor control, such as reoxygenation processes and the redistribution of tumor cells into more radiosensitive phases of the cell cycle. The influence of each individual factor varies across different tissues; however, it is essential to consider all of these elements when developing an effective radiotherapy model. In particular, more comparative studies involving the 5Rs should be conducted across all fields of radiation treatment in order to enable better implementation of personalized, targeted therapies.