Reviews & Analysis

This Review discusses molecular circuitry underlying adaptive plasticity in brain cancer stem cells, highlighting the transcriptional classification of the stem cell state, neoplastic evolution and development of therapeutic resilience, and critical brain-specific microenvironmental inputs with the goal of informing next-generation stem-targeted treatment paradigms.

Nonsense-mediated RNA decay (NMD) is a highly conserved RNA surveillance pathway that selectively degrades both normal and mutant mRNAs harbouring stop codons in specific contexts. In this Review, Tan et al. present recent evidence that NMD has a dichotomous role in tumour growth and progression that supports the future use of NMD-modulatory therapy to treat cancer.

This Review discusses the metabolic alterations and vulnerabilities across multiple types of cancer, and describes how these could potentially be targeted using diet in conjunction with pharmacologic therapies.

This Perspective discusses the role of multicellular tumour networks, formed by tumour microtubes and tunnelling nanotubes, in brain tumours. It also discusses their relevance to therapy resistance and how these networks might be therapeutically targeted, and their potential relevance in other cancer types.

This Perspective discusses how polyamines, polyamine metabolism, the microbiota and the diet interconnect to establish a tumour microenvironment that facilitates the initiation and progression of cancer. It also details ways in which polyamine metabolism and function can be targeted for therapeutic benefit, including specifically enhancing the antitumour immune response.

This Review discusses our current understanding of tumour-infiltrating B lymphocytes (TIL-Bs) in human cancers, considering the role of TIL-Bs across the major facets of cancer immunity. The authors also discuss strategies to harness the cell-based and antibody-based effector mechanisms of TIL-Bs to enable a new generation of cancer immunotherapies.

This Review provides an overview of cancer-related actions of pattern recognition receptors, including both immune and non-immune functions that influence cancer mechanisms as well as the potential to target pattern recognition receptors for cancer drug development and biomarker discovery.

In recent years, research in the field of ferroptosis in cancer has risen steeply in part owing to its potential to be targeted. In this Review, Lei et al. provide an up-to-date synthesis of the roles and mechanisms of ferroptosis in tumour growth and progression, including its function in tumour immunity, highlighting it as a vulnerability that can be exploited for cancer therapy.

Dysregulation of cyclin-dependent kinase 4 (CDK4) and CDK6, regulators of the cell cycle, favours the growth and survival of several cancer types. Owing to this, CDK4 and CDK6 inhibitors were developed and are currently approved for the treatment of advanced hormone receptor-positive breast cancer. This Review describes how we are only now beginning to fully understand their mechanisms of action and provides a new framework for conceptualizing their activity, which might enable expansion of the clinical opportunities of these agents.

This Review discusses mechanisms by which tumour ecosystems adapt to therapeutic stresses and how these could be exploited, as well as challenges associated with tumour heterogeneity. It provides an integrative framework to identify and target vulnerabilities that arise from adaptive responses to overcome cancer therapy resistance.

This Review discusses how senescence can be induced in cancer cells and how distinctive features of senescent cancer cells might be exploited for their selective eradication as a potential cancer therapy.

This Review examines recent developments in proteogenomics, key findings from the proteogenomic analyses of a wide range of cancers and emerging applications of proteogenomics to translational studies and immuno-oncology, as well as discussing future prospects regarding integration into clinical trials and patient care.

The advent of CRISPR technologies has enabled programmable nucleic acid editing in mammalian cells. In this Review, Katti et al. outline the enormous progress that has been made in the application of CRISPR tools to the study of cancer and also describe the potential use of CRISPR systems in clinical cancer management including diagnosis and treatment.

Liquid–liquid phase separation (LLPS) has been revealed as a widespread mechanism underlying the spatiotemporal coordination of biological activities in cells. This Perspective discusses how LLPS shapes the biochemical landscape of cancer cells, providing insight into emerging findings of dysregulated LLPS promoting cancer pathology.

This Review discusses the mechanisms underlying the immune response to melanomas, as well as the mechanisms of response and resistance of these tumours to immunotherapies. The lessons learned in melanoma may apply to other tumour types.

This Review discusses the complex biology of the family of kallikrein-related peptidases and their context-dependent functions in cancer and the tumour microenvironment, as well as their role in tumour immune suppression and resistance to cancer therapy.

Reactive oxygen species (ROS) are highly reactive molecules derived from oxygen during cellular metabolism, which regulate various cell phenotypes. In this Review, Cheung and Vousden outline how pathways controlling ROS production and limitation can contribute to tumorigenesis and how the complexities in the responses of both cancer cells and stromal components to ROS might determine the success or failure of ROS modulating therapies.

Cancer cell-intrinsic PDL1 signals present novel drug discovery targets and also have potential as treatment response biomarkers. This Perspective discusses our understanding of cancer cell-intrinsic PDL1 signals, mechanisms for signal controls and immunopathological consequences including resistance to cytotoxic agents, targeted small molecules and immunotherapies.

Our understanding of ependymomas, which are rare tumours of the central nervous system, has increased substantially over the past 10 years. This Review discusses important biological features of ependymoma as well as key oncogenes, tumour suppressors and epigenetic changes that could potentially be exploited to improve therapy.

This Perspective outlines how the signalling pathways enabling metastasis are often shared with those supporting resistance to cancer therapies. Identifying nodes within these shared signalling networks that could be targeted might result in more effective therapies for the treatment of rapidly growing solid tumours.