Articles in 2013

Cancer of unknown primary site is both a challenging clinical problem and a disease that provides potential insight into the mechanisms that underlie early metastasis.

Potassium channels are transmembrane proteins that selectively facilitate the flow of potassium ions down an electrochemical gradient. Their roles in cell proliferation, angiogenesis and cell migration have only recently been assessed. Thus, the potential importance of these channels for tumour biology is only now becoming evident.

A paper inNaturereports the design of small molecules that can irreversibly bind to and block the activity of oncogenic KRAS-G12C, but not wild-type KRAS.

A new study by Emerling and colleagues has shown that phosphatidylinositol 5-phosphate 4-kinase type-2α (PIP4K2α) and PIP4K2β are essential for the growth of p53-null cells and may represent a pharmaceutical target for cancers that have non-functional p53.

Although survival rates for most paediatric cancers have improved at a remarkable pace over the past four decades, the vast majority of these cancer survivors will have at least one chronic health condition by 40 years of age. How can we best understand and treat the long-term morbidity and mortality that is associated with currently successful treatments?

Three groups have sequenced samples of ER-positive and hormone therapy-resistant breast cancers and found point mutations inESR1, the gene encoding ERα.

A coordinately published set of papers inNature, Nature Geneticsand other journals report data from up to 5,000 individual cancers, including cancers of the breast, uterus, ovaries, lung, brain, head and neck, colon and rectum, bladder, kidney and blood.

The bone marrow microenvironment can support the growth and activity of leukaemia stem cells, and two recent papers suggest several ways in which these interactions might be targeted for therapeutic benefit.

Mammalian basic HLH (helix–loop–helix)–PER–ARNT–SIM (bHLH–PAS) proteins are heterodimeric transcription factors. Recently determined structures of their PAS domains and successful small-molecule screening programmes are now providing new opportunities to discover selective agonists and antagonists directed against this multitasking family of transcription factors.

The roles of vascular endothelial growth factor (VEGF) in cancer go beyond effects on the vasculature. VEGF signalling in tumour cells, which is mediated by VEGF receptor tyrosine kinases and the neuropilins, contributes to many aspects of tumorigenesis, as highlighted in this Review.

The processes of intravasation and extravasation are thought to be crucial for cancer cell dissemination and metastasis. This Review describes how cancer cells cross the endothelial barrier, with a focus on the extravasation step.

A new study identifies the tumour suppressor folliculin as a GTPase-activating protein that regulates the nucleotide status of the RAG proteins, which are important regulators of mTOR complex 1 kinase activity.

Several studies have recently highlighted a crucial role for adenosine signalling in regulating various aspects of the cell-intrinsic and cell-extrinsic processes of cancer development. This Review critically discusses adenosine and its effects on immune, endothelial and cancer cells during the course of neoplastic disease.

A paper by Dmitry Bulavin and colleagues shows that WIP1 is involved in regulating DNA methylation-mediated silencing of heterochromatin and might contribute to C-to-T substitutions and mutation load in breast cancers.

Evolutionary life history theory posits that some organisms reproduce rapidly whereas others invest more resources in survival. This framework might help us to understand the diversity of phenotypes that are displayed by tumour cells, including stem cell-like phenotypes, and could have important clinical implications.

Three papers report the discovery of recurring deleterious mutations in the cohesin subunitSTAG2in urothelial bladder cancers, but the evidence for the contribution of STAG2 loss to aneuploidy is conflicting.