When turned on, the gene p53 turns off cancer. However, when existing drugs boost p53, only a few tumors die — the rest resist the challenge. A new study shows how: tumors that live even in the face of p53 reactivation create more of the protein p21 than the protein PUMA; tumors that die have more PUMA than p21. And, for the first time, the current study shows a handful of genes that control this ratio.