According to a story from Newswise, scientists have previously discovered that there are two pathways that colorectal polyps may utilize as they transform into colorectal cancer. These are dubbed the ‘conventional’ and ‘alternative’ pathways. The alternative pathway, which is linked to about 15 to 30 percent of cases, causes a more dangerous form called serrated colorectal cancer that is resistant to treatment. The latest research has revealed that the disappearance of two genes appears to be responsible for the appearance of this type.
About Colorectal Cancer
Colorectal cancer, which is also known as colon or bowel cancer, appears in the large intestine. There are a number of potential risk factors that can increase a person’s risk of getting colorectal cancer, such as inflammatory bowel disease, an inactive lifestyle, old age, being male, smoking, a diet high in fat, processed meat, alcohol, and red meat, obesity, and family history. Some patients often do not present with symptoms early in the disease; when symptoms appear, they can include fatigue, bloody stool, changes in bowel movements, weight loss, constipation, loss of appetite, rectal bleeding, and nausea/vomiting. Treatment options for colorectal cancer include surgery, immunotherapy, chemotherapy, and radiation therapy. The five year survival rate in the US is 65 percent. Screening for this cancer is recommended by age 50 or even earlier. To learn more about colorectal cancer, click here.
Research Findings
Colorectal cancer is not generally rare, particularly in developed countries, but serrated colorectal cancer is less common. The discovery that the loss of two genes can lead to this type has also revealed potential biomarkers that could be valuable in the treatment of the cancer. The researchers also identified a possible combination therapy, which they tested in a mouse model of the disease. The two genes that were identified are protein kinase C zeta and protein kinase C lambda/iota.
In animal models, mice without these genes got serrated colorectal cancer. The expression of the two genes was also reduced in tissue samples from human patients with the disease. Serrated colorectal cancer tumors were also identified as being in an “activated” state, which is characteristic of aggressive tumors; they also expressed PD-L1, which that allows the tumor to escape immune system attack.
With this knowledge, mice with the disease were treated with a TGF-beta receptor inhibitor, which “deactivates” the tumor, and an anti PD-L1 compound that allowed the immune system to attack the tumor. This combination appeared to be effective in treating the mice.
The findings also suggest that patients with inflammatory bowel disease may be at greater risk for serrated colorectal cancer, because people these diseases often have reduced expression of protein kinase C lambda/iota.
Check out the original study here.
