Articles in 2020

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.

Johnstone, Reyes et al. find that colorectal cancer cells undergo substantial compartmental reorganization and that this likely supresses, rather than promotes, tumorigenesis.

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.

Two studies have now provided evidence of differences, dependent on patient sex, in oncogenic features, such as frequencies of driver gene mutations, mutation load and mutational signatures, as well as immune selection.

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.

Gomes et al. show that age-dependent upregulation of levels of the metabolite methylmalonic acid (MMA) in serum from healthy donors can promote tumour progression in mice via SOX4-dependent regulation of cell fate decisions.

Disseminated cancer cells in the cerebrospinal fluid of leptomeningeal metastasis not only face survival on limited resources but must also escape activation of an immune response. Chi et al. suggest cancer cells can accomplish this by outcompeting macrophages for an essential micronutrient, iron.

Li, W., Hu, J., Shi, B. et al. showed that the appropriate phase separation property of the protein AKAP95 was required for its regulation of splicing and expression of cancer-related genes, thereby contributing to tumorigenesis.

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.

Koelwyn et al. investigated the connection between cardiovascular events and cancer progression and found that systemic changes induced by myocardial infarction can promote breast tumour growth and increase the risk of cancer-specific death.

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.

Two papers in Nature Medicine report studies that validate the utility of cell-free methylated DNA analysis for early detection of renal cell carcinomas and diagnosis of central nervous system tumours.

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.

Aitken et al. have used mutagen-induced liver tumours to trace individual strands of the DNA double helix to which damage occurred and correlate this with mutational patterns to inform upon tumour evolution.

Using a rapid mass-spectrometry based approach to analyse aerosol released during surgical cauterization of tumour tissue, Koundouros et al. derived metabolic signatures associated with the tumour genotype. Based on these signatures, they identified a new mechanism by which oncogenic PI3K signalling promotes tumour growth.

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.

This Review discusses our current understanding of adaptive and innate immune cell metabolism in the context of the tumour microenvironment, providing insight into the interaction of cancer cell metabolism and immune metabolism, as well as the potential for leveraging metabolic vulnerabilities to enhance the antitumour immune response.