Nature Cancer, Published online: 01 October 2026; doi:10.1038/s43018-026-01254-8

TP53 gene alterations are common cancer drivers and a focus of intense translational and clinical research. However, effective p53-targeted therapies remain elusive. This Clinical Outlook examines the evolving clinical landscape, highlighting recent advances and emerging strategies for improving outcomes in TP53-mutated malignancies.