Researchers at the University of Florida College of Medicine have discovered how common age-related changes in the blood system can make certain colon cancers grow faster. The study, to be published August 24 in the Journal of Experimental Medicine (JEM), also suggests how these effects might be therapeutically targeted to reduce tumor growth and improve patient survival.
As we age, the hematopoietic stem cells that reside in the bone marrow and give rise to all of the body’s different blood cells gradually acquire mutations in their DNA. Most of these mutations have no effect, but some can enhance a particular stem cell’s ability to survive and proliferate, resulting in large numbers of blood cells that carry the same mutation. This phenomenon, known as clonal hematopoiesis, is seen in 10–20% of elderly people and is associated with an increased risk of developing blood cancers. But clonal hematopoiesis is even more frequently seen in patients with many other types of cancer outside of the blood system and is associated with faster tumor progression and shorter survival times.
Guryanova and colleagues decided to investigate the role of clonal hematopoiesis in colitis-associated colon cancer (CAC). Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, is a well-known risk factor for colon cancer, and clonal hematopoiesis is prevalent in both IBD and colon cancer patients.
The researchers generated mice with clonal hematopoiesis by transplanting them with blood stem cells lacking one copy of Dnmt3a, the most frequently mutated gene in clonal hematopoiesis patients. The mice were then treated with drugs that induce the development of CAC. Guryanova’s team found that CAC occurred more frequently, and developed more rapidly, in mice with clonal hematopoiesis, resulting in larger tumors with a worse histopathology.
Guryanova and colleagues determined that one way clonal hematopoiesis promotes the development of CAC is by increasing the number of blood vessels that supply the intestinal tumors with the nutrients and oxygen they need to grow. Blocking the formation of these extra blood vessels with axitinib, a drug approved by the FDA to treat advanced kidney cancer, inhibited the growth of CAC tumors in mice with clonal hematopoiesis. In contrast, axitinib had little effect on the growth of CAC tumors in mice without clonal hematopoiesis.
(RN/Newswise)
