Browse Articles

Three-dimensional bioprinted cancer models could revolutionize understanding and treatment of cancer. Neufeld, Yeini and Pozzi discuss how such models can reveal novel biomarkers and drug targets, illuminate mechanisms of tumorigenesis and interactions between tumour, stromal and immune cells, and advance personalized cancer therapy.

‘Ductal carcinoma in situ’ (DCIS) describes abnormal cells in the milk ducts. DCIS is often non-invasive, although a small proportion of cases leave the ducts and progress to invasive breast cancer. This Review discusses the existing data for distinguishing progressive and non-progressive DCIS, with a focus on informing current disease management strategies.

The gut microbiota has been shown to regulate responses to various cancer therapies, and the microbial species involved and their underlying mechanisms have begun to be unravelled. In this Perspective, Fernandes and colleagues present this evidence and then outline how it could be used to develop microbiota-based therapies for patients with cancer.

In this Tools of the Trade article, Venkataramani describes the development of in vivo imaging workflows that allow the acquisition of imaging data with improved signal-to-noise matched to single-cell RNA-sequencing data.

Kalkavan et al. find sublethal cytochrome c release leads to a caspase-independent, ATF4-dependent drug-tolerant persister phenotype.

Using single-cell RNA-seq and functional analysis in prostate cancer organoids and mouse models, Chan et al. identify inflammatory JAK–STAT signalling to drive the transition of adenocarcinomas to neuroendocrine prostate cancer.

Luo et al. uncover strong associations between the tumour microbiome and race, a finding that further emphasises the need for race diversity in cancer studies.

Wright et al. reveal how methotrexate binds to the human reduced folate carrier and outline key features that will aid the rational design of targeted antifolate therapeutics.

In this Tools of the Trade article, Luigi Ombrato describes the development of Cherry-niche, a cell labelling system, which enables the unbiased identification of cancer cell-neighbouring cells.

This Perspective outlines the preclinical emergence of smart cell therapeutics, which when paired with machine learning analysis of genomic data could be implemented in the clinic to both enhance tumour recognition and prevent tumour escape.

Ma et al. demonstrate that platelets suppress liver tumour growth in the context of non-alcoholic fatty liver disease through T cell-dependent antitumour immunity.

Xu, Yan et al. show that the hypothalamic–pituitary unit produces α-melanocyte-stimulating hormone in tumour-bearing mice, to promote myelopoiesis and immunosuppression.

In this Tools of the Trade article, Daniela S. Thommen describes the development and use of a patient-derived tumour fragment (PDTF) platform wherein surgically resected tumour lesions are cultured ex vivo, which enables patients’ responses to immunotherapy to be more faithfully modelled.

Using a reporter system in a mouse model of pancreatic cancer, Baslan et al. detail the progression of genomic disruption following p53 loss.

In two studies published concurrently, Pal et al. and Shi et al. reveal that certain gliomas rely on the de novo synthesis of pyrimidines. These studies go on to demonstrate the effectiveness of brain-penetrant inhibitors of de novo pyrimidine synthesis in preclinical models of glioma.

Clinical trials of immunotherapies have so far failed to demonstrate efficacy in high-grade serous ovarian cancers. Here, Kandalaft et al. classify high-grade serous ovarian cancers into distinct immunophenotypes that might account for these failures and could also provide a rational basis for tailored immunotherapy in the future.

Chen et al. have developed a preclinical platform that enables the reprogramming of locoregional macrophages and microglia in situ with CD133-directed chimeric antigen receptors, which leads to the phagocytosis and removal of residual glioma stem cells after tumour debulking.

Barkley and colleagues conducted single-cell RNA sequencing of almost 20,000 malignant cells and identified cancer cell states that are both common and different across tumour types, and revealed how these states interact with the tumour microenvironment.

Seki et al. show that exposure to cold suppresses tumour growth in mice through increasing glucose uptake and thermogenesis in brown adipose tissue.

The increasing size of cancer datasets requires new ways of thinking for analysing and integrating these data. In this Review, Jiang et al. discuss considerations and strategies for wielding ‘big data’ ― large, information-rich datasets ― in basic research and for translational applications such as identifying biomarkers, informing clinical trials and developing new assays and treatments.