Fragility of precision: resistance to mutant p53 reactivation

In a recent study published in Cancer Discovery , Fece de la Cruz et al. 1 show that cancer patients treated with rezatapopt, a Y220C-selective mutant p53 reactivator, rapidly acquire diverse secondary TP53 mutations. These findings confirm on-target activity in patients and highlight how the molecular precision of tumor suppressor reactivation creates evolutionary fragility.