In this Review, Dey and colleagues discuss the key findings from studies of Hippo pathway signalling across biological processes and diseases, and discuss new strategies and therapeutic implications of targeting this pathway.

RAS proteins, which are frequently altered in cancer, were once considered undruggable, but compounds targeting some mutant RAS proteins have recently demonstrated clinical efficacy. In this Review, Malek and colleagues explore how these and other drugs that target RAS or associated pathways might be used effectively, particularly in combinations, and discuss other RAS-targeted therapies in the pipeline.

Several biological phenomena alter the ageing process. This Review discusses the most promising agents to slow ageing, separating them into two tiers based on their efficacy and evidence. The potential use of some interventions in clinical trials to expand overall healthspan as well as how those interventions could be assessed are also discussed.

This Review highlights the challenges of using mouse models to advance drug discovery in Alzheimer disease, discussing the emerging opportunities to optimize disease modelling and alternative preclinical research systems to test therapeutic approaches in this highly prevalent disease.

Primary stem cells have long been used therapeutically for applications such as bone marrow transplantation. This Review discusses how cell-engineering approaches are enabling the development of next-generation stem cell therapies with improved function, specificity and responsiveness, thereby expanding their applications into areas such as delivering drugs and oncolytic viruses to tumours and promoting tissue repair in various diseases.

Many G protein-coupled receptors (GPCRs) have endogenous peptide agonists, and modifying the sequence of these peptides has led to some successful therapeutics. In this Review, Davenport and colleagues discuss strategies to generate effective GPCR-targeted peptide therapeutics by introducing chemical novelty, extending plasma half-life, improving a therapeutic’s drug-like properties or generating biased ligands. These approaches could overcome some of the challenges in developing peptide therapeutics.