The 3rd-generation thiosemicarbazone COTI-2 functions similarly through both p53-mediated pathways and p53-independent redox homeostatic mechanisms (43) and has entered a Phase II clinical trial (NCT02433626), although it is of note that thiosemicarbazone cancer drug candidates have known nonspecific cytotoxicity and effects on iron metabolic pathways (44). This evidence concerns the gene TP53 and cancer.