Cell Cycle Effects in Radiation Oncology

Abstract

Cells in the human body can be either dividing or nondividing. In order to undergo cell division, the cycling cells sequentially enter four different cell cycle phases: G1, S, G2, and M. It has long been known that cells in different cell cycle phases display different radiosensitivity. Cells in late S phase are usually most radioresistant and cells in M phase most radiosensitive. One of the classical four “R”s describing the rationale behind fractionated radiotherapy is based on such cell cycle differences, as fractionation allows tumor cells in a radioresistant cell cycle phase to “Redistribute” into more radiosensitive phases before the next fractions. Furthermore, some chemotherapeutic or targeted drugs applied in combination with radiation therapy can cause the tumor cells to accumulate in radioresistant or radiosensitive cell cycle phases, thereby altering the tumor radiosensitivity. It is also well known that radiation halts cell cycle progression through inducing arrest at the cell cycle checkpoints. Three major radiation-induced cell cycle checkpoints exist, in G1, S, and G2 phase. Because most irradiated tumor cells do not die before attempting to divide, the checkpoints are important to allow time for repair of the radiation damage. The G1 checkpoint is dependent on the tumor suppressor p53 and is often deficient or lacking in tumor cells. Tumor cells may therefore rely more on the S and G2 checkpoints for repair of radiation damage compared to normal cells. One strategy for obtaining tumor selective radiosensitization is thus to combine radiation with drugs that abrogate the G2 checkpoint.