Perspectives in 2018

Genomic instability in cancer models presents a major challenge in the design and reproducibility of research and its clinical translation. This Opinion article discusses the causes and consequences of intra-tumour genomic heterogeneity and instability in commonly used models and implications thereof.

This Opinion argues that understanding the interactions between cells that occur in tumours requires concepts from evolutionary game theory. Game theory can provide insights into the stability of cooperation among cells in a tumour and how this might be used therapeutically.

This Opinion describes cell-in-cell processes in cancer, providing insight into their functional purpose in tumour tissue. Entosis is a unique process in which cancer cells are actively invaded by other cells, conferring them a competitive advantage that may drive cancer evolution.

In this Opinion, Li et al. put forward the idea that there is a narrow window or ‘sweet spot’ in which oncogenic RAS signalling can promote tumour initiation in normal cells and present the evidence that RAS mutation patterns are the product of selection for optimal RAS mutations to achieve the ideal level of signalling.

This Opinion discusses the potential of fasting and fasting-mimicking diets to help overcome toxicities induced by anticancer therapy. The differential response of normal and cancer cells undergoing starvation is argued to make normal cells less sensitive to therapy-induced toxicity, while cancer cells become more sensitive to therapy-induced cell death.

This Opinion provides insight into the potential of targeting the replication stress response in cancer and discusses the strategy of inhibiting ataxia telangiectasia and Rad3-related protein (ATR) and the need for reliable biomarkers to enable patient stratification.

This Opinion proposes that temporal variations in intratumoural blood flow are the result of eco-evolutionary dynamics. It describes adaptive strategies to stochastically varying environments that may strongly affect observed cancer phenotypes and clinical outcomes including formation of metastases and response to treatment.

This Opinion discusses the role of the primary cilium as a platform for pathways implicated in cancer and how changes in the ciliation of cells in the tumour microenvironment can affect cancer progression.

In this Opinion, Joshi et al. argue that in cancer cells, a state of chaperome hyperconnectivity is obtained by increasing the interaction strength among chaperome machinery members. These chaperome scaffolding platforms act to increase the functional diversity of oncogenic processes and have implications for the development of chaperome inhibitors.

In this Opinion article, Hosny et al. discuss the application of artificial intelligence to image-based tasks in the field of radiology and consider the advantages and challenges of its clinical implementation.

In this Timeline article, Maman and Witz describe how much progress has been made in understanding how the tumour microenvironment influences tumour progression since its initial description, highlighting the controversies in the field and the potential of targeting components of the microenvironment for cancer therapy.

In this Opinion article, Twumasi-Boateng et al. discuss the use of oncolytic viruses as multiplexed immune-modulating platforms with the potential to improve the effectiveness of immunotherapies through novel synergistic mechanisms promoting antitumour immune activity.

This Opinion discusses studies indicating a direct role of RB in chromatin regulation and DNA repair. The authors propose that a non-canonical RB pathway exists, which is independent of the function of RB in cell cycle regulation and which contributes to cancer progression.

This Opinion article highlights how activating mutations in the gene encoding oestrogen receptor-α (ERα), a major driver in breast cancer, undermine structural features of wild-type ERα that maintain the ‘off-state’ in the absence of oestrogens, thus making ERα constitutively active and endocrine-therapy resistant.

This Opinion argues for a new look at the role of ABC transporters in cancer multidrug resistance to push forward their clinical application as biomarkers and as targets in combination therapies in order to improve anticancer drug efficiency.

This Perspective provides an update on targeted therapy development for neuroblastoma and proposes that clinical trial design needs to be rethought in order to provide rigorous, evidence-based assessment of these new therapies in this rare and often deadly paediatric tumour.

In this Opinion article, Seluanov et al. discuss the diverse mechanisms of cancer resistance found in long-lived mammals and argue that studies of unconventional long-lived and cancer-resistant animal species could provide breakthroughs in cancer therapy and prevention.