Regarding colon cancer, several studies have demonstrated in vitro and in tumor xenografts that HIPK2 inhibition: (i) increases tumor progression and reduces tumor response to therapies through inactivation of the p53 apoptotic activity; (ii) induces VEGF production and angiogenesis by means of HIF-1, β-catenin or COX-2 activation; (iii) induces a pro-inflammatory phenotype that favors tumor progression and immune evasion; and (iv) induces CAF differentiation in the tumor–host interaction. This evidence concerns the gene TP53 and colonic neoplasm.