Articles in 2019

Gene gating is the tethering of genes to nuclear pores to facilitate rapid nuclear export of transcripts. Scholz et al. show that gene gating of MYC increases nuclear export and overall expression of MYC transcripts in human colon cancer cells.

This Focus issue highlights current research into the unique biology of brain tumours and brain metastasis and how this research might improve therapy of these often devastating diseases.

Lin et al. and Lambo et al. report in-depth therapeutic screening and genomic profiling, respectively, of two types of aggressive paediatric central nervous system tumours, and both groups identify vulnerabilities of these tumours that might be exploited therapeutically.

Moya et al. have uncovered a non-cell autonomous, tumour suppressive mechanism of competition driven by the Hippo pathway effectors YAP and TAZ in peritumoural hepatocytes that limits liver cancer in mice.

This Review summarizes the epidemiology literature linking data-driven and investigator-defined dietary patterns to cancer risk, providing expert appraisal of new developments in the field and highlighting both emerging mechanistic insights and key areas for future research.

The majority of cancers arise in individuals over the age of 60. This Review discusses how ageing tissues through changes in the extracellular matrix as well as in the functions of fibroblasts and immune cells can impact tumour initiation, progression and response to therapy.

This Review discusses recent genomic, epigenomic, transcriptomic and proteomic profiling studies of human medulloblastoma that have advanced our understanding of its disease subgroups. These efforts have provided new insights into the diverse biology of medulloblastomas that will hopefully lead to improved diagnosis and therapy.

This Review discusses altered cellular metabolism in gliomas, with particular regard to the interaction between tumour genotype and the brain microenvironment, and how advances in studying glioma metabolism have contributed to the discovery of potential drug targets.

This Review discusses how advances in our understanding of the immune system within the brain have implications for the successful implementation of immunotherapy to treat brain tumours, despite challenges such as effective delivery, target specificity and intratumour heterogeneity.

This Review discusses the role of bodily fluids and their underlying forces and imposed stresses in metastasis, highlighting the contributions of fluid mechanics to tumour cell intravasation, intravascular arrest and extravasation as well as to dissemination of tumour-derived factors.

In this Viewpoint article, we asked four experts to provide their opinions on important aspects of brain metastasis biology, focusing on the unique microenvironment and therapeutic targets in the brain, preclinical models and how studying brain metastases could inform primary brain tumour biology.

Strickley, Messerschmidt et al. show that beta human papilloma virus (β-HPV) infection itself is not causal in cutaneous squamous cell carcinoma (SCC) development in the context of immunosuppression — instead, the loss of β-HPV-mediated T cell immunity promotes SCC.

Two papers report the discovery and preclinical analyses of two different covalent inhibitors of KRAS-G12C (AMG 510 and MRTX849) as well as the first data on the efficacy of these inhibitors in cancer patients.

This Review discusses the PI3K–AKT signalling network and its control of cancer cell metabolism through both direct and indirect regulation of nutrient transport and metabolic enzymes, thereby connecting oncogenic signalling and metabolic reprogramming to support cancer cell survival and proliferation.

Research by Chemi at al. highlights the potential of using pulmonary venous circulating tumour cells from patients with NSCLC, collected during tumour resection, to predict relapse and to explore mechanisms of early dissemination.

This Review discusses the complex and context-dependent role of the complement system in cancer, highlighting the opposing effects of complement activation in both promoting and restraining tumour progression. A novel analysis of publicly available transcriptomic data to provide an overview of the prognostic value of complement gene expression in cancer is also included.

In this Perspectives article, the authors outline the preclinical and clinical evidence for epithelial–mesenchymal plasticity (EMP) in cancer progression and metastasis, focusing on recent challenges and controversies, and highlight strategies to therapeutically target the EMP process.

To date, studies investigating mechanisms of therapy resistance have primarily focused on tumour-intrinsic changes, yet it is now clear that host responses to different cancer therapies can contribute to tumour regrowth, spread and resistance to therapy. This Review discusses the recent advances in understanding host-mediated pro-tumorigenic responses to cancer therapy, with an emphasis on therapy-induced immunological, angiogenic and metastatic effects.

The microbiome is more than just bacteria. Now, the groups of Deepak Saxena and George Miller at New York University have linked alterations in the fungal component of the pancreatic microbiome, which activate the complement cascade, to pancreatic ductal adenocarcinoma growth and progression

Burr et al. report an evolutionarily conserved, tumour-intrinsic role for Polycomb repressive complex 2 (PRC2) in the epigenetic silencing of MHC class I antigen presentation pathway genes, illustrating that cancer cells can co-opt the immunomodulatory functions of PRC2 to evade immune surveillance.