Prophylactic use of colchicine in preventing radiation induced coronary artery disease.
Radiation therapy is one of the primary treatments in fighting breast cancer, one of the most common cancers in the US. One of the dose limiting factors of this therapy is radiation induced heart damage that results from mediastinal radiation. Recently statins, a medication typically used to lower cholesterol levels, have been suggested as a prophylactic treatment to potentially mitigate this process. Similarly, we hypothesized whether colchicine, an anti-inflammatory medication that is presently used in the treatment of gout and pericarditis, might be used to prevent coronary artery disease induced by radiation therapy. We hypothesize that colchicine may help prevent the deleterious effect on coronary arteries induced by radiation therapy by inhibiting inflammation and platelet aggregation. The pathophysiology of radiation induced coronary artery disease is similar to that of coronary artery disease in the general population. Inflammation, fibrosis and platelet aggregation play a key role in this process. After radiation therapy, inflammation occurs, recruiting leukocytes, particularly neutrophils and monocytes. Neutrophils are fibrotic mediators, and macrophages form foam cells in the intimal layer of the vessel wall, leading to the build-up of atherosclerotic plaques. Platelet aggregation, both initially and upon plaque rupture, is also a culprit in exacerbating radiation damage. Colchicine is known to inhibit microtubule polymerization and therefore inhibits mitosis, neutrophil motility and has been shown to decrease platelet aggregation. Its anti-inflammatory properties have been attributed to several different effects based on microtubule dysfunction. Colchicine has also been shown to affect the expression of adhesion molecules on endothelial cells, leukocytes, and to decrease activation of thrombin induced platelet aggregation. There is evidence to suggest that colchicine may be beneficial in the treatment of radiation induced coronary artery disease due to its anti-inflammatory and anti-coagulant properties. This idea would be beneficial for future studies.