Bevacizumab is used in metastatic colorectal cancer. It is a monoclonal antibody targeting VEGF-A. The predominant mechanism by which bevacizumab enhances the efficacy of co-administered chemotherapy (beyond direct antitumour effects) is:

• A Upregulating P-glycoprotein in tumour endothelial cells to reduce chemotherapy efflux from the tumour vasculature
• B Inducing apoptosis of tumour endothelial cells, creating pores that allow chemotherapy to access the tumour stroma
• C Normalising the chaotic tumour vasculature by pruning immature vessels, transiently improving drug delivery and reducing interstitial fluid pressure ✓
• D Activating tumour-infiltrating lymphocytes by blocking PD-L1 expressed on VEGF-stimulated endothelium

Explanation

Bevacizumab's synergy with chemotherapy involves a concept called 'vascular normalisation'. Tumour vasculature is structurally abnormal (leaky, tortuous, poor pericyte coverage) causing elevated interstitial fluid pressure and hypoxia that impair drug penetration. Blocking VEGF-A pruning of immature vessels transiently normalises vascular architecture, reduces IFP, and improves oxygenation and drug delivery during a therapeutic window. This paradoxically enhances chemotherapy access despite reducing total vessel density. P-glycoprotein efflux is not modulated by bevacizumab; PD-L1 blockade is immunotherapy (pembrolizumab), not bevacizumab.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.