Volume 24 Issue 11, November 2025

Can Pfizer’s GDF15-blocking, appetite-boosting antibody ponsegromab address a cancer-induced wasting syndrome — and help patients live longer in the process?

Chemical modification represents an effective strategy to improve the stability, efficiency and specificity of RNA therapeutics, while reducing their immunogenicity. This Review discusses approaches for manufacturing three major categories of RNA — small RNA, translatable RNA and CRISPR guide RNA — and assesses chemical modifications being applied to their broad therapeutic applications. Clinical examples and potential future opportunities are discussed.

The Hippo signalling pathway fulfils a vital role in the regulation of tissue homeostasis and organ development and its dysregulation is associated with several diseases. This Review provides an overview of Hippo pathway signalling and regulation, highlighting its biological functions and role in diseases. Recent advances and future directions in the development of Hippo pathway-targeted therapies, primarily in cancer, are discussed.

Medicinal chemistry optimizations in the progression from hit to lead to drug candidate affect properties of small-molecule drugs such as their molecular weight and lipophilicity. This Perspective analyses the properties of orally administered small-molecule drug candidates reported in the period 2015–2022 and their corresponding hit and lead compounds, and compares them with the properties of drug candidates identified between 2000 and 2010 and their hits and leads, with the aim of improving understanding of the evolution of hit finding and optimization strategies.