Gastroenterology

The researches find that the colorectal cancer outcomes may improve by genetically altering an immune-regulatory protein in cancer cells, making the cells more vulnerable to chemotherapy. That’s according to new Mayo Clinic research. The findings; published this month in Oncogene; indicate that increasing the expression of the PD-L1 protein in colorectal cancer cells can improve the effectiveness of chemotherapy.

The colorectal cancer outcomes

“These findings, if verified by subsequent research; suggest that the level of tumor cell PD-L1 may be important in drug sensitivity and suggest that enhancing PD-L1 expression may be a potential strategy to improve treatment outcomes in this malignancy;” says Frank Sinicrope, M.D., a Mayo Clinic medical oncologist and gastroenterologist. Dr. Sinicrope is co-director of the Gastrointestinal Cancer Program at Mayo Clinic and corresponding author of the study.

PD-L1 is an immune checkpoint protein that interacts with another protein, PD-1, to negatively affect cell functions and enable tumor cells to evade the body’s immune system. Therefore Research has shown that interrupting the PD-L1/PD-1 interaction can enhance attacks on anti-tumor immunity. However; the Mayo Clinic study describes another function of PD-L1: its effect on proteins that regulate tumor cell death. Deleting the PD-L1 gene suppress two proteins that are associate with increase chemotherapy-induce cell death. In contrast; restoring PD-L1 expression reversed the suppression of these proteins.

The body’s immune system

“They sought to determine the relevance of our findings for PD-L1 in patients with colorectal cancer;” Dr. Sinicrope says. “To do so, we utilized the Cancer Genome Atlas database of the National Cancer Institute to examine the association of PD-L1 expression with the survival of patients with colon cancer.” Because Colorectal cancer, also called colon cancer or large bowel cancer, includes cancerous growths in the colon, rectum and appendix. With 655,000 deaths worldwide per year, it is the third most common form of cancer and the second leading cause of cancer-related death in the Western world.

Many colorectal cancers are thought to arise from adenomatous polyps in the colon. These mushroom-shaped growths are usually benign, but some may develop into cancer over time. Therefore The majority of the time, the diagnosis of localized colon cancer is through colonoscopy. Therapy is usually through surgery; which in many cases is follow by chemotherapy. The study find that increase tumor cell PD-L1 expression was associated with better survival among patients expect to have received chemotherapy, which is the standard of care for patients with stage 3 and stage 4 cancers, according to Dr. Sinicrope.

“This suggests a broader role for PD-L1 as a possible predictive biomarker for how patients will respond to cancer treatment, though more research is needed to address this issue;” he says. The study also found that the BRAF oncogene, a gene that can transform a cell into a cancer cell; can regulate the expression of PD-L1. When the BRAF oncogene is mutate, it can increase PD-L1 expression in colorectal cancer cells, according to the study.