Dysregulation of inflammatory pathways in human colorectal diseases

Colorectal cancer (CRC) is one of the most common cancers worldwide. CRC is a multifactorial disease due to the combined effect of genetic and environmental factors. The majority of cases of CRC are sporadic and result from risk factors, such as a sedentary lifestyle, obesity, processed diets, alcohol consumption and smoking, but a small percentage is hereditary, estimated at 5-10%. In both, the tumor interacts with heterogeneous cell populations, such as endothelial, stromal and immune cells, secreting different signals (cytokines, chemokines or growth factors) to generate a tumor microenvironment favorable for invasion and metastasis of cancer cells. There is extensive evidence that inflammatory processes play a key role in carcinogenesis and tumor progression in CCR. In fact, CRC arises from 3 major pathways: i) The adenoma‑carcinoma sequence; ii) serrated pathway; and iii) the inflammatory pathway.Different cellular activation profiles of the tumor microenvironment can promote pro or anti-tumor pathways; Genetic alterations cause the dysregulation of signaling pathways leading to drug resistance, the inhibition of apoptosis and the induction of proliferation, invasion and migration, resulting in CRC development and metastasis.A heterogeneous disease, such as CRC resulting from the activation of numerous signaling pathways, is therapeutically challenging, and cannot be targeted with a single agent. A combination of conventional therapeutics with novel inhibitors targeting dysregulated pathways is required for a better outcome.

14/03/2025