Opinion

Nerve invasion frequently occurs in tumours and has traditionally been viewed as a passive process; however, recent studies have revealed active migration of cancer cells along axons (neural tracking). This Opinion article describes possible molecular mechanisms of neural tracking.

This Opinion article discusses the challenges in determining which genomic events in tumours are actionable and thus expected to affect treatment response. The authors summarize published classification approaches and propose a new framework to classify mutation actionability in early-phase clinical trials.

The incidence of many cancer types in non-reproductive tissues is higher in males than in females. This Opinion article discusses the cellular and molecular differences between the two sexes that might contribute to this discrepancy.

Current cancer therapies exert selective pressures that drive the evolution of drug-resistant clones. In this Opinion article, the authors argue that induction of stable tumour reversion represents an alternative strategy that could reduce resistance and thus effectively and durably treat cancer.

This Opinion article discusses the opportunities and challenges for 'precision mouse modelling', including the proposed essential criteria of mouse models for prevention research, representative success stories and opportunities for improved analyses in future studies of precision cancer prevention.

This Opinion article summarizes the evidence supporting the use of aspirin to prevent colorectal cancer. By considering the pathways that mediate the anticancer effects of aspirin, the authors evaluate potential biomarkers that may enable a precision medicine approach to aspirin chemoprevention.

The development of therapeutic approaches that target BRCA-mutant tumours has led to the possibility of expanding the range of patients who may benefit from such strategies. Tumours with 'BRCAness', a similar phenotype to germline BRCA-mutant tumours, are increasingly being identified, and this Opinion article discusses the advances and challenges in this context.

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.

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.

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.

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.

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.

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.

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 Opinion describes the early interactions between immune cells and pre-neoplastic cells observed in translucent zebrafish andDrosophila melanogastermodels, and speculates on their potential implications in human cancer.

In this Opinion article, Brocket al. analyse how intrinsic variability in gene expression in proliferating cells, as well as microenvironmental signals, can drive cells to transform into a neoplastic state or revert to a normalized state.

Inborn errors of metabolism are inherited monogenic disorders caused by mutations in genes encoding metabolic enzymes that can result in malignancy. This Opinion article discusses how studying these rare diseases might provide insight into how specific metabolic changes contribute to cancer initiation, development, diagnosis and treatment.

Heterogeneous expression of the epidermal growth factor receptor (EGFR) in glioblastoma poses an important challenge for the effective use of EGFR-targeted therapies. In this Opinion article, Furnariet al. highlight the possible mechanisms underlying EGFR heterogeneity, and the importance in understanding these mechanisms to improve treatment outcome in glioblastoma.

This Opinion article advocates therapeutically targeting the niches that harbour dormant disseminated tumour cells in order to make them susceptible to cytotoxic agents. Similar strategies have sensitized leukaemic cells and latent HIV to therapy, and such an approach might delay or even prevent metastasis.