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Association between non-angiogenic tumours and resistance has been also illustrated in a different mouse model in which an orthotopic model of hepatocellular carcinoma is initially sensitive to Sorafenib, another Tyrosine Kinase inhibitor blocking the VEGF induced signalling, only to develop resistance after one month, by switching to an invasive phenotype, with upregulation of EMT-associated genes and co-option of sinusoidal and portal-tract vessels [42]