VEGFA and lactic acidosis: PARP-1 inhibition blocks the poly(ADP-ribosyl)ation of c-FOS and c-JUN, leading to p62 downregulation, which is associated with the induction of the CAF phenotype.178 Furthermore, several studies have shown that lactic acidosis in hypoxic tumor tissue can activate TGF-β signaling, which subsequently stimulates neovascularization by regulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases.