Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism

摘要: The impact of discontinuation anti-VEGF cancer therapy in promoting metastasis is unknown. Here we show treatment creates a time-window profound structural changes liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes the fenestrated endothelium loss VE-cadherin. drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation extravasation. Discontinuation an antibody-based sunitinib markedly promotes metastasis. Mechanistically, host hepatocyte, but not cell-derived vascular endothelial growth factor (VEGF), responsible for Deletion hepatocyte VEGF ablates 'off-drug'-induced These findings provide mechanistic insights on cessation-induced raise new challenge uninterrupted sustained antiangiogenic human cancers.