Reviews & Analysis

This Review provides an update of interleukins in tumour biology, covering the milestones of the latest discoveries of interleukin-related mechanisms in cancer, together with their application in clinical practice. It includes an overview of current clinical trials and breakthrough preclinical concepts.

Variation in mitochondrial DNA (mtDNA) is common in certain tumours. This Review discusses the relevance of heritable, somatic and ancient mtDNA variants to cancer and how subtle changes in mtDNA result in metabolic, epigenetic and transcriptional changes that affect carcinogenesis.

Deregulation of chromatin modification underlies a myriad of oncogenic processes. This Review synthesizes the many connections between chromatin modifications and cancer, discussing recent advances and highlighting options for therapeutic targeting.

This Review discusses how long noncoding RNAs influence metastasis by functioning in discrete pro-metastatic steps including the epithelial–mesenchymal transition, invasion and migration and organotrophic colonization, and by influencing the tumour microenvironment. Diagnostic and therapeutic potential as well as controversies and ongoing technical challenges are discussed.

This Review broadly discusses therapeutic cancer vaccines, covering resistance mechanisms and strategies to overcome these, how to improve the antigen repertoire for vaccines and vaccine platforms, and approaches for enhancing immunotherapy efficacy.

An improved understanding of tumour immunology and therapy must assess the systemic immune landscape beyond the tumour microenvironment. This Review outlines peripheral immune cell reorganization in response to tumour growth and therapy, their contribution to immunotherapy responses and their potential as diagnostic or predictive biomarkers.

Autophagy is induced by stress signals in cancer cells as well as immune cells in the tumour microenvironment. This Review discusses how autophagy modulates antitumour immunity in cancer cell autonomous and non-autonomous ways, and potential approaches for targeting autophagy to enhance the antitumour immune response.

Focal adhesion kinase (FAK) is overexpressed in many cancers and is involved in a multitude of oncogenic processes and resistance mechanisms. This Review discusses the rationale and preclinical evidence for FAK-based combination therapies and strategies for future development.

This Review discusses the role of functional (impacting tumour phenotype) and non-functional intra-tumour heterogeneity (ITH) in cancer evolution, highlighting the importance of considering genetic and non-genetic factors and their impact on patient outcomes.

Immune checkpoint inhibition does not benefit all patients. This Review discusses how antigen presentation, which is crucial for the success of this therapy, may be disrupted in tumours and dendritic cells of patients, and how tumours may further evade natural killer cell recognition.

Clonal expansion in phenotypically normal or non-cancer tissues is commonly seen in association with ageing and/or in response to environmental insults and chronic inflammation, but does not necessarily indicate cancer development. This Review discusses recent findings on clonal expansion in these tissues and their biological significance in cancer development, ageing and inflammatory diseases.

Alterations in the extracellular matrix at the biochemical, biomechanical, architectural and topographical levels contribute to the development and progression of solid tumours. Our increased understanding of matrix biology is leading to the development of new approaches that co-target the matrix in cancer, including in metastasis.

Histone variants are critical for maintenance of genome integrity, nuclear architecture and cell identity. Emerging evidence implicates histone variants and their dedicated chaperones in cancer initiation and progression; this Review examines the key players, their mechanisms of action and strategies to target these therapeutically.

This Review outlines the major advances that have been made to the efficacy and safety of chimeric antigen receptor (CAR) T cell therapies over the past 3 years and looks to new findings that will have consequences for the future of this immunotherapy.

This Review describes the metabolic rewiring that occurs in cancer cells transitioning through the metastatic cascade and discusses the evidence for metabolically distinct features of primary tumours and metastases.

Aberrant signalling of ERBB family members plays an important role in tumorigenesis and in the escape from antitumour immunity in multiple malignancies. This Review discusses the mechanisms by which this signalling affects antitumour immune responses and the potential application of immune-genome precision medicine in this context.

This Review discusses the diverse facets of cancer biology that are shaped by aneuploidy and highlights the distinct roles of aneuploidy as both a tumour promoter and an anticancer vulnerability.