Understanding how cell intrinsic and extrinsic factors combine to initiate transformation holds promise for the development of strategies to prevent, detect and treat cancer early. In this Review, Jassim et al. outline the various theories that have currently been proposed for cancer origins, and the determinants of cancer risk upon which they are based.

This Review outlines how the profound intertumoural heterogeneity in immune landscapes of tumours is shaped by cancer cell-intrinsic alterations and highlights how the crosstalk between these two continuously evolving systems not only challenges therapy success of immunomodulatory drugs but also provides the basis for new therapeutic strategies to overcome immune evasion.

Generalist medical artificial intelligence (GMAI) models are gaining momentum in their applications for cancer treatment. In this Comment, Gilbert and Kather advocate for novel regulation of GMAI approaches to ensure patient safety and adequate physician support.

In a recent study published in Nature, Goto et al. explore mechanisms of immune evasion in early colorectal cancers and adenomas and identify SOX17 to be crucial for immune escape through suppression of interferon-γ signalling.

In this recent study, He et al. establish that chronic stress promotes metastasis through stress-induced formation of neutrophil extracellular traps (NETs).

Sánchez-Guixé et al. investigated the possible routes to second malignancies in survivors of paediatric cancer by studying four such clinical cases.

In this Tools of the Trade article, Kaile Wang describes the development and use of Arc-well, a high-throughput single-cell DNA sequencing method tailored to analyse archival formalin-fixed paraffin-embedded (FFPE) materials.