Reviews & Analysis

This Opinion article discusses the contributions of bioengineering, especially biomaterials engineering, to our understanding of cancer biology and to the development of emerging therapeutic strategies such as cancer immunotherapy.

This Review discusses the role of natural killer (NK) cells in immunosurveillance of tumour cells, highlighting the new therapeutic approaches to NK cell targeting in the treatment of cancer and improvement of NK cell-mediated antitumour immune responses.

Understanding how DNA damage determines cell fate — DNA repair and cell survival or death — is important for gaining insight into carcinogenesis and in promoting successful cancer therapy. This Review describes key decision-making nodes in the complex interplay between DNA damage responses and cell fate signalling.

Somatic genetic mosaicism has been demonstrated in many tissues, leading to interactions between functionally diverse cell populations that could contribute to homeostasis ('clonal health') or influence disease states. These authors argue that embryonic somatic mosaicism can contribute to adult cancers.

Research into the DNA damage response (DDR) was recently honoured by the Nobel Prize in Chemistry and the Lasker Award. In this Timeline article, the authors provide a historical perspective on our understanding of the role of the DDR in cancer.

Increased activity and aberrant localization of cysteine cathepsin proteases within the tumour microenvironment have potent roles in driving cancer progression. This Review discusses the roles of cathepsins and provides a roadmap for the rational integration of cathepsin-targeting agents into clinical treatment.

This Review discusses mathematical modelling approaches in cancer research. These models can complement experimental and clinical studies, but can also challenge current paradigms, redefine our understanding of mechanisms driving tumorigenesis and shape future research.

This Review highlights emerging mechanisms of acquired resistance to agents targeting the androgen receptor in castration-resistant prostate cancer, which fall into the three broad categories of restored androgen receptor (AR) signalling, AR bypass signalling and complete AR independence.

Genome-based cancer therapeutic matching is limited by incomplete biological understanding of the relationship between phenotype and cancer genotype. This Opinion article proposes that this limitation can be addressed by functional testing of live patient tumour cells exposed to potential therapies.

Liver tumorigenesis is complex and depends on the cellular origin of a tumour as well as on environmental influences. This Review discusses the origins of various primary liver cancers, integrating our current understanding of cells of origin, liver tumour genomics and the disrupted hepatic microenvironment.

This Opinion article outlines a set of research priorities, based on discussions held at the 2015 Helene Harris Memorial Trust Ovarian Cancer Action meeting, that the authors believe will reduce incidence and improve outcomes for women with high-grade serous ovarian cancer.

What is the best approach to avoid resistance to therapies that target intracellular signalling pathways? In this Opinion article, Gonda and Ramsay argue that increased effort should be made to target transcriptional regulators directly.

This Review discusses recent advances that shed new light on the relationship between centrosomes and cancer, raising the possibility that centrosome aberrations contribute to this disease in different ways than initially envisaged.

Most cancer genomics studies have focused on identifying the most important somatic mutations ('major drivers') that promote tumour growth. However, many cancer-associated mutations might instead have relatively weak tumour-promoting effects. This Opinion article highlights the existence of these mutations (termed 'mini drivers') and the functional effects that they might have.

MEK1 and MEK2 have key roles in tumorigenesis and, therefore, represent promising targets for cancer therapy. This Review discusses the mechanisms of action of different inhibitors of MEK1 and MEK2, the mechanisms of resistance to these inhibitors and their current clinical progress.

The transcription factor MYC upregulates and downregulates distinct sets of target genes, promoting cell growth and proliferation, increased metabolic rate and RNA biogenesis. This Review discusses MYC-mediated transcriptional regulation in normal growth control, as well as in tumour development and maintenance.

Aberrations in gene expression due to an altered epigenotype that is widely distributed in normal tissues are referred to as constitutional epimutations. This Opinion article discusses the potential contribution of constitutional epimutations to the 'missing' causality and heritability of cancer.

This Review discusses the roles of members of the sirtuin (SIRT) family in cancer biology, which have dichotomous, context-dependent functions as tumour suppressors and oncogenes. Furthermore, the authors discuss the possibility of targeting the sirtuins for anticancer therapy.

Activation of the peripheral nervous system can promote metastasis of primary tumours. This Opinion article discusses the molecular mechanisms through which physiological stress can have an effect on cancer, and how pharmacological antagonism of β-adrenergic signalling might represent a therapeutic opportunity to target cancer progression.

This Review discusses nucleotide metabolism and how fluctuations in deoxyribonucleoside triphosphate (dNTP) pools affect genomic instability. Drugs that target this system have been in use for many years and some of these are discussed, as well as newer approaches to manipulating deoxyribonucleotide metabolism for cancer treatment.