Fibrosis is a key characteristic of a range of chronic diseases that has been challenging to target with drugs. This Review highlights core pathways active in fibrotic conditions across organs, as well as specific mechanisms and characteristics of fibrotic diseases in the lung, gut, kidney, skin and liver, and provides proposals for strategies to improve the translation of potential antifibrotic therapies.

Hundreds of computational resources have been developed that can be applied to repurposing existing drugs for new indications, making it challenging to select the right resource for a specific project. To help address this challenge, this article provides an overview of computational approaches to drug repurposing based on a comprehensive survey of available resources classified into hierarchical categories for a web catalogue, and presents an expert evaluation of selected resources, as well as case studies to illustrate their application.

Multiple tumour-agnostic kinase inhibitors have been approved that are clinically effective regardless of tumour location. This Review describes the origins of tumour-agnostic drug development, focusing on small-molecule inhibitors that target kinase pathway aberrations, and discusses the challenges in developing tissue-agnostic agents.

Since its discovery 30 years ago, NRF2 has emerged as a master regulator of cellular homeostasis and has been implicated in a broad range of pathologies. This Review analyses NRF2 regulation, signalling and cross-talk, and assesses the role of this transcription factor in health and disease. The development of therapeutic NRF2 modulators and the associated challenges are also discussed.

New approach methodologies (NAMs) have the potential to progressively transform medicines development by reducing reliance on animal testing while increasing the relevance of nonclinical data to patients. However, achieving regulatory acceptance of NAMs demands enhanced collaboration, clear guidance and continuous, science-based adaptation of the regulatory environment to accommodate emerging innovation.