Overall, BH3 functional profiling of mechanistically heterogeneous TIS phenotypes in A549 (p16-null and p53/BAX-proficient) and LoVo (p16/p53-proficient and BAX-deficient) cancer cells revealed the occurrence of the three major BCL-2/BH3 interactome categories, namely: primed, unprimed-competent, and unprimed-incompetent. Here, TP53 is linked to cancer.