TP53 and cancer: Previous mechanistic studies investigating the role of chronic stress in cancer progression have primarily focused on the hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system.47,48 For instance, Zhou et al. demonstrated that adrenaline produced by the HPA axis promotes CRC stemness through the CEBPB-TRIM2-P53 pathway.49 However, Cao et al. did not report any significant difference in adrenaline and cortisol levels between the intestinal regions of stressed and non-stressed mice,33 suggesting the existence of additional contributing factors that remain unknown.