According to the American Society of Radiation Oncologists, two-thirds of all cancers are currently treated with some form of radiation. Radiation, or "radiotherapy," may be used as the primary treatment or as an adjunct to surgery or chemotherapy. In terminal cancer, radiation therapy may be used palliatively, either to prolong life or to improve quality of life when there is no expectation of cure. Radiation has the following effect on cancer cells in humans.
Growth Arrest
The life cycle of human cells is divided into five phases: G0, G1, S, G2, and M. Normal cells divide infrequently and spend 90% or more of their lifespan in G0, the resting phase. Cancer cells, by contrast, divide continuously and spend all of their time in G1-M. Radiation exerts the most damage on cells in G1-M, making it relatively selective for cancer cells.
This is because during G0, DNA is tightly coiled within the nucleus, with only the most frequently transcribed genes relatively exposed. During the G1-M phases, DNA unfurls, exponentially increasing the surface area that will be exposed to ionizing radiation. This unfurled DNA sustains more severe damage and damage at multiple points compared with nondividing DNA in G0. In particular, unfurled DNA is vulnerable to double-strand breaks through each of the two DNA strands. Although the cell can repair most kinds of damage, it has difficulty with double-strand breaks. When the cell can't repair the damage, the result is cell cycle or growth arrest. The cell will eventually die without reproducing itself.
Apoptosis
For a smaller fraction of cancer cells, the damage induced by ionizing radiation is so catastrophic that it triggers a process known as apoptosis. Apoptosis is programmed cell death in which enzymes in a cellular organelle called a lysozyme essentially cause the cell to digest itself, producing harmless byproducts called "blebs."
Apoptosis is a normal process that occurs when the cell recognizes that is irretrievably damaged. Unfortunately, cancer also renders a cell relatively resistant to apoptosis by allowing it to "override" some of the most common apoptotic signal cascades. In addition, many of the enzymes involved in apoptosis rely on oxygen. However, cancer cells characteristically overgrow their blood supply and therefore exist in relatively oxygen-deprived environments.
Adjuvant Therapy and Directions for Future Research
Radiation results in cancer cell death by one of two means: cell cycle arrest or apoptosis. In growth arrest, the cell is rendered unable to divide, an essential feature of cancer cells. In addition, the lifespan of the cell is usually (but not always) significantly shortened. In apoptosis, cell death occurs within a few hours.
Unfortunately, some cancer cells are able to evade these fates. Some cancer cells succeed in repairing radiation-induced DNA damage and continue to reproduce. Others escape the apoptotic signal cascade.
Currently, radiation oncologists use systemic chemotherapy as an adjuvant to increase the total cell damage and tip the scales in favor of cell death and irreparable DNA damage. Future targets include drugs that selectively target DNA repair enzymes and gene therapy to restore "p53" and other pro-apoptotic genes that are lost or inactivated in more than 90% of cancers.
References
- American Society for Therapeutic Radiology & Oncology. "Radiation Therapy." Encyclopedia of Cancer and Society. 2007
- Sharma RA, Vallis KA, McKenna WG. "Basics of Radiation Therapy". In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG (eds). Abeloff's Clinical Oncology, 4th ed. Churchill Livingstone Elsevier; Philadelphia, PA. (2008)
