Single-cell epigenomic technologies are refining our understanding of cancer evolution. Here Laisné et al. describe how epigenomic heterogeneity generates dynamic reservoirs of tumour cell states, through epigenomic reprogramming and selection among stochastic changes, which can be leveraged in the design of novel therapies.

In this Review, Rabas et al. describe the mechanisms by which primary tumours precondition distal organs to favour metastatic colonization — a limiting step of metastasis — and discuss how non-cancer-dependent perturbations of tissue homeostasis are also able to trigger pro-metastatic conditioning, emphasizing the need for a holistic view to identify preventive or therapeutic opportunities.

In this Tools of the Trade article, Xiaoxuan Meng describes the development of cf-EpiTracing, a highly sensitive and automated epigenetic liquid-biopsy platform that captures histone modifications on cell-free chromatin from plasma, enabling unbiased monitoring of cancer.

Colitis predisposes to colorectal cancer, but how inflammation promotes tumour initiation has remained unclear. Nagaraja et al. show that inflammatory injury imprints a heritable epigenetic memory in colonic stem cells that enhances AP-1-driven proliferative programs and accelerates malignant outgrowth following oncogenic mutation.

Microplastics and nanoplastics (MNPs) are increasingly recognized as pervasive environmental exposures. Li et al. analysed human brain tumour samples and post-mortem healthy brain tissue to quantify MNP burden, and characterize particle composition and spatial distribution.

The established link between congenital anomalies and cancer could lead to improved surveillance and therapeutic strategies. However, we must first expand population-based studies to confirm these patterns, along with detailed molecular assessments to identify risk markers and deeper patient profiling to support precision medicine.

In this Tools of the Trade article, Zhengyuan Pang describes the development and use of volumetric clearing-assisted tissue click chemistry (vCATCH), a pipeline that enables mapping of covalent drug binding at cellular resolution across a mouse body.

In a recent study, Gudenas et al. map pineoblastoma subgroups to pinealocyte progenitors and identify a shared photoreceptor-like transcriptional network across pineoblastoma, retinoblastoma and group 3 medulloblastoma, revealing a developmental vulnerability with therapeutic potential.