We then evaluated whether combined inhibition of vessel co - option and angiogenesis is more effective at limiting tumor growth when compared to angiogenesis inhibition alone . Mice with established control - or ARPC3 - knockdown tumors were treated with the VEGF - A inhibitory antibody B20 - 4.1.128 combined with capecitabine ( Fig . 6f - h ) . In control tumors , which have a predominantly replacement HGP ( Fig . 6f ) , no significant inhibition of tumor burden was observed in response to treatment when compared to vehicle control ( Fig .   6 g ) . However , in ARPC3 knockdown tumors , which have a predominantly desmoplastic HGP ( Fig . 6f ) , tumor burden was significantly suppressed by treatment ( Fig . 6 g ) . In addition , although treatment with B20 - 4.1.1 led to a reduced tumor vessel density in both control - and ARPC3 knockdown - tumors , this effect was more pronounced when vessel cooption was suppressed by knockdown of ARPC3 ( Fig . 6h , Supplementary Fig . 14 ) . The administration of capecitabine alone did not significantly suppress tumor burden or tumor vessel density in either control - or ARPC3 - knockdown tumors ( Supplementary Fig . 15 ) . These data suggest that simultaneous inhibition of angiogenesis and vessel co - option may be a more effective strategy for the treatment of advanced liver metastases than current strategies which target angiogenesis alone .