Reviews & Analysis

This Review highlights the different genetic pathways impacted by germline mutations that can lead to the development of familial and sporadic haematological malignancies, with a particular focus on recent advances in acute lymphoblastic leukaemia, acute myeloid leukaemia and myelodysplastic syndromes.

This Review examines recent developments in the molecular and translational aspects of bladder cancer biology and discusses their current or potential future clinical applications in the management of bladder cancer.

The hostile microenvironment of the tumour can disrupt endoplasmic reticulum (ER) homeostasis in cancer cells and infiltrating immune cells to result in a state of ER stress. This Review discusses how ER stress can influence not only the pro-tumoural features of cancer cells but also reprogramme the function of innate and adaptive immune cells, creating vulnerabilities that could be targeted by emerging therapeutic strategies.

This Review discusses protein kinase C (PKC) isoforms in cancer, in particular focusing on their functional properties in the context of tumour suppression or promotion, target validation, PKC pharmacology and therapeutic exploitation.

Platinum chemotherapy agents remain among the most widely used anticancer drugs, but there is still room to maximize their efficacy. This Review discusses newer findings related to sensitivity and resistance to these drugs as well as recent advances in platinum drug development.

Activation of WNT–β-catenin signalling via mutations is a recurrent driver event in human cancer. In this Review, Bugter et al. discuss the influence of different mutational subsets of WNT tumour suppressor genes on cancer growth, clinical outcomes and treatment approaches.

This Review discusses the metabolic regulation of 2-oxoglutarate-dependent dioxygenases (2OGDDs) and how dysregulation of 2OGDDs in cancer, by genetic aberrations or environmental factors including hypoxia and/or the action of oncometabolites, can contribute to tumour development and growth.

This Review discusses how altered processing or activity of coding and non-coding RNAs contributes to cancer, introducing the regulation of gene expression by coding and non-coding RNA and discussing both established and emerging roles for RNAs in cancer.

This Perspective discusses how therapeutic resistance is not only driven by genetic evolution but often involves non-genetic adaptive mechanisms that are intimately linked. Acknowledging these adaptive processes will enable the development of innovative strategies to monitor and counteract non-genetic therapy resistance as well as provide novel therapeutic avenues.

Metastatic dissemination can occur early during cancer progression, yet clinically overt metastases are often not detected for many years after surgical removal of the primary tumour. In this Perspective, Klein argues that understanding the ‘invisible’ phase of metastatic colonization is necessary to explain this phenomenon and develop better therapies to prevent metastasis.

This Review discusses the potential use of cancer-derived extracellular vesicles for cancer biomarkers and novel therapeutics, with a focus on evolving translational applications, and their roles during cancer progression.

This Review discusses the role of comparative oncology studies between pet dogs and humans with an emphasis on selected canine tumour types that represent those with the most translational benefit to humans and those possessing important molecular intersections with human malignancies.

This Review discusses the current understanding of how insulin and insulin receptor signalling contribute to cancer growth, in the context of the rising prevalence of obesity and diabetes worldwide and the realization that hyperinsulinaemia may contribute to therapeutic failures.

Perturbations of circadian rhythms can promote cancer, and expression of core clock genes and proteins is attenuated in many tumours. Furthermore, metabolic control by the circadian clock may influence cancer metabolism. This Review outlines recent discoveries related to the interplay between circadian rhythms, proliferative metabolism and cancer.

This Review discusses how the disease biology of many sarcomas is driven by chromatin pathway alterations ranging from dysregulation of DNA methylation, histone modifications and nucleosome remodelling to disruption of higher-order, 3D chromatin structure, with a view to use this knowledge to better develop targeted therapies for patients with sarcoma.

This Review provides a brief historical perspective of our understanding of the role of cancer genes before presenting the Integrative OncoGenomics (IntOGen) platform, a bioinformatics method of mutational driver identification, which is beginning to reveal the compendium of driver genes across many tumour types as well as alluding to their tumorigenic mechanisms.

This Review discusses the main immune parameters positively or negatively shaping cancer development, and their prognostic and predictive value. The authors advocate the need to assess a combination of immune determinants and the importance of evaluating the functional status of specific cell populations to increase prognostic and/or predictive power.

This Review discusses the emerging dual role played by neutrophils in the tumour microenvironment as part of tumour-promoting inflammation, while also mediating antitumour immune responses, and suggests that neutrophil function could be manipulated in myeloid cell-based therapeutic approaches to improve patient outcomes.

This Review outlines how eosinophils influence the tumour microenvironment and examines the diverse pro-tumorigenic and antitumorigenic functions of these cells. It also discusses the use of eosinophils as predictive biomarkers and effector cells in immunotherapy.

This Review discusses functional screening strategies in mice, which use genetic perturbation or chemical mutagenesis to delineate genomic and regulatory features in oncogenesis, metastasis and drug resistance, which might in turn help to identify targetable cancer vulnerabilities.