The blind spot of p53

Inactivation of the p53 tumour-suppressor pathway is a common feature of human cancers, prompting suggestions that restoring p53 function in established tumours might be an effective therapy. However, two papers in this week’s Nature highlight a practical limitation of p53-directed cancer therapeutics. They show in a K-Ras-driven lung-cancer model that p53-mediated tumour suppression is engaged only at a late stage of tumour progression, when the K-Ras oncogenic signal reaches a threshold that is sufficient to activate the ARF-p53 pathway. This means that p53 re-expression fails to restrict the early stages of tumorigenesis, although it does induce regression of more aggressive tumours.