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Circulating tumour cells (CTCs) offer a minimally invasive biopsy strategy for prostate cancer monitoring. This Review discusses the use of CTCs at all stages of prostate cancer development and treatment, from CTC isolation and enrichment strategies to the prognostic and clinical utility of these cells in prostate cancer.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Single-cell studies of human white adipose tissue (WAT) provide insights into the specialized cell types in the tissue. Here the authors combine publicly available and newly generated high-resolution and bulk transcriptomic results from multiple human datasets to provide a comprehensive cellular map of white adipose tissue.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Cancer of unknown primary is difficult to treat due to high heterogeneity in treatment response depending on the original site. Here, the authors use DNA methylation data to develop a machine learning classifier to predict the tissue of origin from a single blood draw, allowing potential treatment changes to improve efficacy.

AgRP neurons of the arcuate nucleus of the hypothalamus promote homeostatic feeding yet are rapidly suppressed by food-related sensory cues. The authors identify a population of inhibitory DMH-LepR neurons that relays real-time information about the nature and availability of food to dynamically modulate ARC-AgRP neuron activity and feeding behavior.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Adipocyte-expressed long non-coding RNAs (lncRNAs) have been shown to regulate the transcription of genes involved in lipid metabolism. Here the authors describe a human adipocyte-specific lncRNA, ADIPINT, which regulates lipid metabolism in white adipocytes in part through its interaction with the metabolic enzyme pyruvate carboxylase.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

Maqdasy, Lecoutre et al. show that increased an phosphocreatine/creatine ratio in white adipocytes drives changes in AMP-activated protein kinase activity and promotes white adipocyte inflammation during obesity.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Most human gene promoters are embedded within CpG islands that lack DNA methylation and coincide with sites at which histone H3 lysine 4 is trimethylated (H3K4me3 sites). Here, a zinc-finger protein, Cfp1, is found to be associated with non-methylated CpG islands and H3K4me3 sites throughout the genome in the mouse brain. A primary function of non-methylated CpG islands might be to genetically determine the local chromatin modification state by interaction with Cfp1 and perhaps other CpG-binding proteins.

The three-dimensional structure of pericentromeres in budding yeast is defined by convergent genes, which mark pericentromere borders and trap cohesin complexes loaded at centromeres, generating an architecture that allows correct chromosome segregation.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

The emergence of acquired resistance to standard platinum-etoposide chemotherapy in small cell lung cancer (SCLC) is a common event. Here, the authors using paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models reveal a mechanism of drug resistance in SCLC mediated by Notch and nitric oxide activation of soluble guanylate cyclase signalling.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

TD-60 (RCC2) structurally resembles a guanine nucleotide exchange factor (GEF), but its target GTPase was unknown. Here Papini et al.show that TD-60 is a GEF for RalA, and that RalA helps to regulate the chromosomal passenger complex and kinetochore–microtubule interactions in mitosis.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

Current outcomes are reported from the ongoing National Lung Matrix Trial, an umbrella trial for the treatment of non-small-cell lung cancer in which patients are triaged according to their tumour genotype and matched with targeted therapeutic agents.

Yuan and colleagues developed an artificial intelligence-based method to derive growth patterns and morphological features from hematoxylin and eosin-stained slides of lung adenocarcinoma samples, for improved tumor grading and patient prognostication.

Dive and colleagues develop an approach for genome-wide cell-free DNA methylation profiling, which can sensitively detect small cell lung cancer in liquid biopsy of patient samples, including stage I disease and molecularly defined SCLC subtypes.

Simpson et al. present a living biobank of 38 small cell lung cancer circulating-tumor-cell-derived explants and use them to study tumor heterogeneity. These models can be used further to study SCLC biology, progression and therapy responses.