Articles in 2020

Wieland et al. report that the tumour microenvironment of human papillomavirus (HPV)-positive head and neck squamous cell carcinomas contains HPV-specific B cells that actively secrete HPV-specific antibodies.

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.

Li, He and Peng et al. show how pancreatic inflammation and KRAS mutation cooperate to initiate neoplasia in a transient progenitor cell population.

Banh et al. show that peripheral axons of sensory nerves release serine into the tumour microenvironment, which can support the growth of extracellular serine-dependent pancreatic ductal adenocarcinoma by promoting mRNA translation.

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.

There is evidence of a mounting mental health crisis among researchers, which may be exacerbated by the COVID-19 pandemic. This Comment article discusses what cancer researchers and institutions can do to promote good mental health and wellbeing within their research communities.

Using single-cell multiomics, Zhou et al. show that somatic copy number alterations (SCNAs) are prevalent in non-epithelial cells from colorectal cancers and normal tissues. Tumours were enriched for fibroblasts with SCNAs, in particular whole chromosome 7 gain.

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.

Cerezo-Wallis et al. show that the melanoma-secreted growth factor midkine drives an inflamed, immunosuppressive tumour microenvironment, by promoting tumour-associated macrophage phenotypes that induce CD8⁺ T cell dysfunction.

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.

Riva et al. exposed mice to a range of 20 known or suspected human carcinogens and then profiled the mutational signatures that arose in the tumours induced by them, finding that surprisingly the majority of the chemicals were not directly mutagenic.

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.

Smith, Whitehall et al. report evidence that somatic mutations in mitochondrial DNA that increase with age in the colorectal epithelium and that reduce oxidative phosphorylation can promote colorectal tumorigenesis.

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.