Volume 24 Issue 9, September 2025

Neutrophils are abundant in the tumour microenvironment and often correlate with poor prognosis. This Review explores neutrophil subtypes — including those with antitumour activity — their polarization potential and mechanisms influencing tumour progression. Therapeutic targets and signalling pathways are discussed, alongside clinical trials assessing neutrophil-targeted approaches on patient outcomes.

The gut microbiome is a key modulator of immunotherapy efficacy. This Review discusses clinical advances in microbiome profiling, recent trials of microbiome-based interventions and the challenges of translating these findings into the clinic. Future directions for optimizing microbiome-targeted therapies in oncology are outlined, including safety, efficacy and patient stratification. 

New approach methodologies (NAMs) offer the promise of greater predictivity of potential safety risks of drug candidates, especially for newer types of therapeutics for which animal models alone have limited or no applicability for safety testing. This article identifies four categories of drug candidate for which NAMs are applicable and discusses progress in their use based on case studies from recent projects, as well as initiatives to promote the advancement and use of NAMs for more human-relevant safety assessment.