Through dynamic deacetylation of both histone (e.g., H3K9, H4K16) and non-histone substrates (e.g., p53, STAT3, HIF-1α), HDACs mechanistically govern six hallmark cancer pathways: (1) cell cycle progression via CDK inhibitor silencing, (2) apoptosis resistance through Bcl-2 family modulation, (3) DNA damage tolerance by repair factor inactivation, (4) autophagic flux dysregulation, (5), VEGF-driven angiogenesis, and (6) EMT-mediated metastatic dissemination. Here, VEGFA is linked to cancer.