Ionizing radiation is used extensively to treat many different types of cancer. Especially considering that increased cancer risk follows radiation exposure, the idea that radiation can be used as therapy to fight cancer is intriguing. We will explore how radiation therapy works and why it is sometimes ineffective.
Cancer is defined by unregulated cell growth and division, and many treatments include a combination of chemotherapy, radiation therapy, and surgical removal. Thus, while surgery involves the physical removal of the tumor or even entire organs, the mechanisms of the other treatments can be more complex. Chemotherapy often impairs cell division, thereby damaging or killing cells that divide quickly throughout the body. On the other hand, radiation therapy is typically localized to the affected region and also affects cell division by damaging DNA.
Radiation therapy involves administration of ionizing radiation from an external source, from a source placed inside the body (brachytherapy), or through the use of radioactive drugs (systemic). The ionizing radiation, which forms ions in the cells of the tissues it passes through thereby killing the cells or altering their DNA, comes in two major types: photons (the most common source and comes from cobalt, cesium, or a linear accelerator) and particles (electrons, protons, neutrons, α particles, and β particles). Electron and most particle beams are used for tumors close to the body surface because they do not go deeply into tissues. On the other hand, proton beams are a newer application that causes little damage to tissues they pass through but kill cells at the end of their path, possibly resulting in fewer side effects. [1]
How does the ionizing radiation kills cells and damage DNA? When the cells are ionized, free radicals and reactive oxygen species (ROS) form. Free radicals are simply atoms, molecules, or ions with unpaired electrons, and ROS is a subset of free radicals that involve oxygen. These agents are very chemically reactive due to their free electron. [2] Due to this high reactivity, free radicals and ROS are likely to attack the covalent bonds of the DNA and other cells they encounter, and these reactions typically occur in chains. Enough injury in the cell will result in apoptosis, or programmed cell death. At the same time, if enough DNA is damaged, the cells will be unable to replicate. Thus, when the radiation targets the tumor cells, the affected cells will die or be unable to proliferate, effectively reducing or eliminating the cancer. [3]
Though radiation therapy has often resulted in remission of cancer, recurrence is fairly common. Recent research has found that this might be due to cancer stem cells producing higher level of antioxidant proteins than other cancer cells. The antioxidants capture and disarm ROS before they cause too much damage. Thus, even though it seems that most of the cancer cells have been killed, some cancer stem cells remain and proliferate over time due to the antioxidant defense against ionizing radiation. [4]
Though radiation is a widely accepted treatment, it can potentially have a counterproductive effect due to the effect of radiation on healthy cells. The radiation works to kill cells it encounters, which is a positive result if the encountered cell is cancerous. However, there remains the risk that the radiation will affect other surrounding cells that are healthy. Radiation exposure of vital healthy tissues near the tumor could induce a secondary cancer near the first. [5] In fact, research has shown that a low energy 6 MV dosage using IMRT (a common source of radiotherapy) shows a 15% increase of radiation-induced cancers, while higher energy dosages show larger increases in secondary cancers. For example, a 15 MV IMRT dosage shows a 20% increase in probability of secondary cancer, and an 18 MV dosage shows a 60% increase in probability. [6] For this reason, one major challenge to technologists is to increase the specificity and focus of the delivery of the radiation, so as not to affect non-cancerous cells.
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[1] "Radiation Therapy Principles," American Cancer Society, September 2011.
[2] Y. Z. Fang, S. Yang and G. Wu, "Free Radicals, Antioxidants, and Nutrition," Nutrition 18, 872 (2002).
[3] R. J. Brooker, Genetics: Analysis and Principles, 4th Ed (McGraw-Hill, 2011).
[4] M. Diehn et al., "Association of Reactive Oxygen Species Levels and Radioresistance in Cancer Stem Cells," Nature 458, 780 (2009).
[5] "Second Cancers Caused by Cancer Treatment," American Cancer Society, 30 Jan 12.
[6] U. Schneider et al., "The Impact of IMRT and Proton Radiotherapy on Secondary Cancer Incidence," Strahlenther. Onkol. 182 647 (2006).