Colorectal Cancer

Colorectal cancer is one of the most common malignancies worldwide, and its mortality rate accounts for the third highest tumor-related deaths. Its early symptoms are not significant and 20-25% of patients already have distant metastases by the time colorectal cancer is diagnosed. The common sites of metastases are the liver and lung, and other metastases include bone, brain, and peritoneum. Although brain metastases from colorectal cancer are not common, once they occur, patients' prognosis is extremely poor, with a 5-year survival rate of only 5-10%.

Figure 1. Metastatic patterns in colorectal cancer as determined by the vascular theory. (Mjahed, R. B., et al., 2022)

The underlying tumor microenvironment and molecular mechanisms

• Molecular biology studies have found that the molecular biology of brain metastases is roughly the same as that of primary colorectal cancer, with a high concordance of KRAS, BRAF, and PIK3CA, and the incidence of KRAS mutations is about 56.5%.
• CXCL4 is more strongly expressed in primary colorectal tumors and its ligand CXCL12 is highly expressed at common sites of metastasis in colorectal cancer, and CXCL4 expression in both primary and metastatic tumors correlates with distant metastasis and overall survival.
• CD44 is an integral membrane glycoprotein that acts as a receptor for extracellular matrix glycans. CD44 is frequently expressed in primary brain tumors and brain metastases. Fatty acid synthase inhibits the CD44 signaling pathway and reduces brain metastasis in colorectal cancer.
• Matrix metalloproteinases (MMP) are zinc endopeptidases that degrade extracellular matrix proteins. MMP degrades type I collagen, laminin, and fibronectin, assisting tumor cells to cross the basement membrane of the blood-brain barrier and enhancing the migration of tumor cells. Selective MMP inhibitors significantly reduce the incidence of experimental brain metastases.

Treatment strategies for colorectal cancer brain metastases depend on the number and location of lesions and include local treatments such as surgery, stereotactic radiosurgery, or whole-brain radiotherapy. New treatment modalities are slowly entering this contraindicated and unapproved field, including in particular monoclonal antibodies, tyrosine kinase inhibitors, or combinations of these agents.

• Monoclonal antibodies.
• PARP inhibitors.
• Monoclonal antibodies targeting the extracellular structural domain of HER-2.
• Immunotherapy targeting PD-1/PD-L1 is a potential treatment option.
• Blood-brain barrier permeation enhancement. Transient disruption of the blood-brain barrier itself using hypertonic solutions can increase blood-brain barrier permeability to ensure better access to the central nervous system for larger monoclonal antibodies.

By providing technical services for colorectal cancer brain metastases, Alfa Cytology is contributing to the advancement of more research on colorectal cancer brain metastases, and we hope to bring better prospects for the treatment of colorectal cancer brain metastases. Please feel free to contact us for information on new cytotoxic drugs, molecularly targeted drugs for brain metastases from colorectal cancer.

Reference

1. Mjahed, R. B., et al. (2022). "Where Are We Now and Where Might We Be Headed in Understanding and Managing Brain Metastases in Colorectal Cancer Patients? " Curr Treat Options Oncol, 23(7): 980-1000.