Review Articles in 2019

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.

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.

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.

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.

This Review discusses the structure and function of the blood–brain barrier (BBB) and how brain tumours and brain metastases compromise BBB integrity. It also discusses the challenges the BBB poses for cancer therapy and how these might be overcome.

The research autopsy is an underused approach to investigate fundamental questions in cancer biology. This Review discusses the rationale for using research autopsies in cancer research, highlighting how this approach has improved knowledge of cancer biology and its tremendous potential to inform future precision medicine strategies.

Methionine uptake and metabolism contributes to cancer pathogenesis through functions in methylation reactions and one-carbon metabolism. This Review discusses methionine metabolism in the context of nutrition and the potential of targeting methionine metabolism in cancer through dietary or pharmacological intervention.

This Review discusses the various approaches that are being explored to target transcription factors in cancer, with many of the inhibitors developed from such approaches now advancing to early clinical trials.

Previous nanomedicine approaches have attempted to concentrate the action of cytotoxic therapies at tumours, generally with limited success. This Review discusses how the field is evolving to use nanoparticles and biomaterials to program the location, pharmacokinetics and co-delivery of immunotherapies, eliciting responses that cannot be achieved upon administration of such compounds in solution.

Innate immune checkpoints, including those regulating tumour detection and phagocytosis, have emerged as potential cancer immunotherapy targets. This Review discusses the role of phagocytosis checkpoints in cancer immune evasion, highlighting the preclinical and early clinical evidence supporting phagocytosis checkpoint blockade.

This Review discusses how circulating tumour cell (CTC) analysis at single-cell resolution provides unique insights into tumour heterogeneity that are not revealed by analysis of circulating tumour DNA (ctDNA) derived from liquid biopsies.

Human germ cell tumours are a heterogeneous group of neoplasms that occur in the gonads and extragonadal sites along the midline of the body. This Review outlines a developmental pathogenetic model for the origin of all germ cell tumours, which is based on the unscheduled reprogramming of cells of the early embryo and germ line.

Co-occurring genomic alterations contribute to the heterogeneity of driver oncogene-defined non-small-cell lung cancer subgroups. This Review discusses the effects of co-mutations on the pathogenesis, biology, microenvironmental interactions and therapeutic vulnerabilities of non-small-cell lung cancer.

Endometrial cancer is histologically and molecularly complex, and effective clinical strategies for aggressive forms of the disease are needed. This Review discusses the identification and potential use of molecular features of endometrial cancer for early detection, treatment and risk stratification.

Paediatric solid tumours are known to be divergent from adult malignancies. This Review describes the molecular landscape of paediatric solid tumours, the therapeutic vulnerabilities that can be targeted and the preclinical models available to test the efficacy of investigational drugs with a view to accelerating translational progress.