Antiangiogenic Therapies in Metastatic Colorectal Cancer

Angiogenesis, the formation of new blood vessels, is a central driver of tumour growth and metastatic spread in colorectal cancer. Therapeutic strategies targeting vascular endothelial growth factor (VEGF) signalling have transformed the management of metastatic disease by inhibiting endothelial proliferation and reducing tumour perfusion. Monoclonal antibodies such as bevacizumab, aflibercept and ramucirumab bind VEGF ligands or receptors to prevent angiogenic signalling, while small-molecule tyrosine kinase inhibitors block downstream kinase activity. These agents have demonstrated improvements in progression-free and overall survival when combined with standard chemotherapy regimens such as FOLFIRI and FOLFOX. Despite these gains, primary and acquired resistance remain major challenges. Research has therefore focused on predictive biomarkers—from genetic polymorphisms to circulating tumour DNA and radiomic signatures—to personalise antiangiogenic therapy and anticipate treatment failure. Emerging combinations with novel tyrosine kinase inhibitors and optimisation of treatment sequencing aim to overcome adaptive resistance and extend clinical benefit. Ongoing efforts to integrate functional imaging, biomarker-driven patient selection and new molecular targets promise further improvements in the management of metastatic colorectal cancer.

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Antiangiogenic Therapies in Metastatic Colorectal Cancer publication trend

The graph below shows the total number of articles in antiangiogenic therapies in metastatic colorectal cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Angiogenesis: The physiological process of new blood vessel formation, exploited by tumours to secure nutrients and oxygen.

Vascular endothelial growth factor (VEGF): A family of signalling proteins that promote angiogenesis by binding to VEGF receptors on endothelial cells.

Monoclonal antibody: A laboratory-produced molecule designed to bind specifically to a target antigen, such as VEGF or VEGF receptors.

Tyrosine kinase inhibitor: A small-molecule drug that blocks the intracellular kinase activity of receptor tyrosine kinases involved in signalling pathways.

Predictive biomarker: A biological measurable indicator that forecasts the likely benefit from a specific therapy, aiding in personalised treatment selection.

References

1. Prediction of Response to Anti-Angiogenic Treatment for Advanced Colorectal Cancer Patients: From Biological Factors to Functional Imaging. Cancers (2024).
2. A phase I/II study of nintedanib and capecitabine for refractory metastatic colorectal cancer. JNCI Cancer Spectrum (2024).
3. Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study. Annals of Oncology (2017).