BCL2 and colorectal carcinoma: By contrast, low p53 often reflects TP53 deletion, loss-of-function mutation, or enhanced degradation, all of which are associated with aggressive tumor behavior in CRC and perhaps override any pro-apoptotic influence of PUMA [22,34,49,50,51] Cohort-specific patterns may include BAX dysfunction, altered BCL-2 family activity, or post-translational disruption of PUMA, any of which may further uncouple PUMA abundance from apoptotic competence [22,48,49].