Reviews & Analysis

Opinions on where we should progress next with cancer research are diverse. In this article, four top cancer researchers from across the globe discuss their thoughts on the current state of cancer research and what progress might be expected in the next 10 years.

RING finger proteins constitute the largest class of ubiquitin protein ligases (E3s). These function to specifically ubiquitylate target proteins. As discussed in this Review, many RING finger proteins are deregulated in cancer.

β-D-N-acetylglucosamine (GlcNAc) is a post-translational protein modification that has increasingly appreciated roles in many cancer-relevant cellular processes. This Opinion article discusses our current understanding of this modification in cancer biology and in the regulation of transcription factors and chromatin.

Cancer is a complex disease, as has been amply shown by the mass of recently generated 'omics' data. Can the new US National Cancer Institute Physical Sciences-Oncology Centers initiative help us to better understand the complexity of this disease?

Dysregulated pH is emerging as a hallmark of cancer because cancers have a 'reversed' pH gradient, with a constitutively increased intracellular pH that is higher than the extracellular pH. This Perspective highlights the central role of pH sensor proteins in facilitating the adaptations that occur in cancer cells.

RNA-binding proteins include essential regulators of microRNA (miRNA) biogenesis, turnover and activity. RNA–RNA and protein–RNA interactions are essential for post-transcriptional regulation in normal development and could be deregulated in disease. This Review highlights the implications of these complex layers of regulation in cancer initiation and progression.

Chemotaxis confers directionality to migrating tumour cells away from the tumour and recruits various cells to the tumour. This Review discusses the mechanisms of chemotaxis and how this process contributes to tumour progression.

The ubiquitous second messenger Ca²⁺is a crucial regulator of cell migration. This Review discusses recent data on ORAI1, STIM1 and TRP, which have been implicated in tumour cell migration and the metastatic cell phenotype.

Perturbation of oestrogen receptor (ER) subtype-specific expression has been detected in various types of cancer, and these differences correlate with the clinical outcome. The selective restoration or ablation of their activity is one of the major therapeutic approaches for hormone-dependent cancers.

Sarcomas are increasingly classified according to the genetic abnormalities associated with their pathogenesis. What are the mechanisms of sarcomagenesis and how might these genetic abnormalities lead to improved therapy for patients?

Is the ability of D-type cyclins to activate cyclin-dependent kinases an effective means of targeting these oncogenes, and how might the patient subgroups that are most likely to benefit be identified?

The nucleosome remodelling and histone deacetylase (NuRD) complex has been implicated in the regulation of transcriptional events that are integral to oncogenesis and cancer progression. This Review discusses how inappropriate localization of the complex could contribute to tumour biology.

This article describes the importance of key physical and mechanical processes at each step of the metastatic cascade. The emerging insight into these physical interactions may lead to new approaches to developing cancer diagnostics and therapies.

Interstrand crosslinks (ICLs) are a type of DNA damage that is induced by various chemotherapeutics, such as cisplatin. This Review discusses how these lesions are repaired through multiple pathways, including the Fanconi anaemia pathway, and how ICL repair mediates sensitivity to these drugs.

Senescence is becoming increasingly appreciated as a powerful mechanism of tumour suppression. This Opinion article discusses how senescence may be capitalized on for therapeutic benefit, and includes the defining features of senescence signalling pathways and the potential molecular strategies and considerations for senescence induction.

This article introduces some preliminary mathematical models of the basic decision circuits in breast cancer cells, with a view to understanding in greater detail their susceptibility or resistance to endocrine therapy.

Recent studies have identified frequent inactivating mutations in different SWI/SNF subunits in several types of cancer, highlighting the tumour suppressor roles of these chromatin remodellers. This Review discusses the current knowledge regarding inactivating mutations, and silencing, of SWI/SNF subunits in cancer, the molecular mechanisms of their tumour suppressor functions and possibilities for therapeutic intervention in SWI/SNF-mutant cancers.

Research into basic developmental biology has frequently yielded insights into cancer biology. This is particularly true for the Hedgehog (HH) pathway, and both naturally occurring and synthetic inhibitors of HH signalling show great promise. However, it remains unclear how many cancers will ultimately benefit from these new, molecularly targeted therapies.

Hypoxia is common in developing and advanced tumours and could therefore provide a means for drug selectivity. As discussed in this Review, this can be achieved either by using prodrugs that are activated in hypoxic regions, or by directly targeting hypoxia-induced signalling pathways that confer survival to tumour cells.

When cancer metastasizes to bone, considerable pain and deregulated bone remodelling occurs, greatly diminishing the possibility of cure. Understanding how metastasizing tumour cells mobilize and sculpt the bone microenvironment to enhance tumour growth and promote bone invasion has uncovered new therapeutic opportunities.