Extrachromosomal DNA (ecDNA) is now accepted as a major contributor to cancer pathogenesis. In this Review, Yan, Mischel and Chang highlight the recent advancements in ecDNA research, providing new insights into the biogenesis and maintenance of ecDNA, as well as its role in altering gene expression and promoting tumour heterogeneity.

Sex differences impact various non-reproductive organ cancers, often leading to higher cancer incidence and poorer outcomes in male individuals. In this Perspective article, Xiao, Lee et al. outline the biological factors contributing to sex bias in immuno-oncology, emphasizing the need for future research to offer a fuller understanding of sex disparities in cancer.

Ageing is a well-accepted risk factor for developing cancer. Yan et al. used a preclinical rat model to study the mechanisms facilitating the age-associated increase in breast tumorigenesis.

In this Tools of the Trade article, Carly Tyer describes the development of Telo-seq, a method to enrich and sequence all telomeres within a sample, and highlights its use in distinguishing between the two telomere maintenance mechanisms used in cancer cells.

In this Journal Club, Sabarinathan discusses a study suggesting immunoproteasome expression as a potential biomarker of response to immune checkpoint inhibition in melanoma.

In this Tools of the Trade article, Siyu He describes the development of Starfysh, a computational toolbox that integrates histology of complex tissues in spatial transcriptomic data analysis to characterize cell states.

In a recent study published in Cell, Chhabra et al. identify age- and sex-dependent changes in skin fibroblasts that drive melanoma aggressiveness, with aged male fibroblasts promoting a slow-cycling, invasive state and resistance to targeted therapy in melanoma cells.

Chibaya, DeMarco et al. investigated a combinatorial approach of delivering innate immune agonists and RAS pathway-targeted therapies to remodel the tumour microenvironment and improve PDAC drug response.