Molecular Aspects of Radiotherapy

ABSTRACT

When tumor cells are exposed to ionizing radiation, various and complicated molecular biological changes take place leading to cell death, mutation, and recovery from sublethal damage. It has been known that DNA is the major critical target of radiation leading to cell death. The radiation-induced DNA damage activates ATM/ATR which then lead to activation and phosphorylation of downstream molecular signals, such as p53. Phosphorylation of p53 leads to inhibition of cell cycle progression, cell death through apoptosis and repair of damaged DNA. Recent evidence clearly demonstrated that p53 is directly involved in activation of cell cycle checkpoints resulting in G1 arrest and G2 arrest. During these arrests, the damaged DNA are repaired. However, when the radiation-induced DNA damage is excessive, cells undergo apoptotic cell death. Here again, p53 is involved in activation of pro-apoptotic signals such as Bax and caspases and inactivation of anti-apoptotic signals such as Bcl-2. Proper activation or intervention of these molecular signals may enable us to enhance the radiation damage in cancer cells and improve the efficacy of radiotherapy of malignant cancer.