Fig. 8: Schematic of ETV5-mediated anti-VEGF therapy resistance in ETV5+ CRC.

In CRC, ETV5 could promote angiogenesis via the secretion of VEGFA and CCL2. When ETV5+ CRC was treated with Bevacizumab, paracrine CCL2 could induce angiogenesis by activating the MAPK and AKT pathways in human umbilical vein endothelial cells, ultimately resulting in Bevacizumab resistance. Therefore, a combination using Bevacizumab and antiCCL2 treatment could synergistically suppress angiogenesis by simultaneously neutralizing ETV5-induced VEGFA and CCL2 in CRC, and this combined therapy might provide promising anti-angiogenic strategy for ETV5+ CRCs.