The Biologic Effect of Radiation
Radiation exerts its biologic effect mainly by directly and indirectly damaging the critical target, DNA, within the cell. As it travels through the patient, radiation deposits energy that produces ionizations (principally by interacting with water molecules in the cell), which results in the breaking of chemical bonds and damage to intracellular molecules. With sufficient accumulated radiation damage to the DNA backbone that tumor cells are unable to adequately repair, the cancer cells undergo cell death, or a process whereby they can no longer replicate. Tumor and normal cells demonstrate differential radiosensitivity which can ideally be harnessed to achieve a therapeutic effect (tumor kill) within an acceptable range of toxicity to normal tissue, also known as the therapeutic index.
Used with permission from Macmillan Publishers Ltd: Nature Reviews Cancer, 4: 737-747, copyright 2004
In fact, many traditional chemotherapy drugs similarly work by affecting DNA synthesis or function, although the various mechanisms whereby various classes of chemotherapy lead to tumor cell kill is complex and dependent on a number of factors including cell cycle phase, time of drug exposure, cell population kinetics and other drug resistance and sensitivity mechanisms.
A number of factors have been observed to modify the responses of cells and tissues to radiation. Oxygen is the best characterized modifier of radiation sensitivity, and a hypoxic tumor microenvironment is more resistant to radiation than well-oxygenated conditions, where higher levels of cell kill can be achieved through production of free radicals from water molecules, indirectly leading to DNA damage. To this end, a number of agents have been developed to affect the tumor microenvironment and enhance the sensitivity of tumor to the effects of radiation, with varying results. Newer classes of drugs that specifically target the mechanisms that promote tumor growth and survival have emerged, with a number of agents demonstrating an improvement in outcome, prolonged survival and often less toxicity than traditional chemotherapy.
