Reviews & Analysis

Inherited inactivating mutations inBRCA1 or BRCA2seem to cause a similar predisposition to breast and ovarian cancer, but a closer look reveals many differences as well. This Perspective discusses the similarities and differences between BRCA1 and BRCA2 and their effects on cancer phenotypes.

Metastasis accounts for the vast majority of cancer deaths. The potential of using nanoparticles to diagnose and to treat metastatic cancer is highlighted in this Review.

The regulation of cell polarity has pleiotropic effects on cell morphology and function, which has implications for tumorigenesis and tumour progression. This Review discusses how polarity complexes affect tumour cell biology and their crosstalk with other important cancer pathways.

The α-subunits that form the oxygen-sensitive component of the hypoxia-inducible factor (HIF) transcription factor have unique and overlapping roles in mediating cellular responses to hypoxia. Surprisingly, they can also have opposing roles, and the differences between HIF1α and HIF2α are discussed in this Review.

Recent evidence indicates that successful cancer clones must have overcome programmed cell removal. In this Opinion article, the authors explore the role of programmed cell removal in both normal and neoplastic cells.

Human cell engineering has made considerable progress, but where to insert foreign sequences in the human genome to maximize safety and efficacy is still uncertain. This Opinion article discusses genomic safe harbours, which are chromosomal locations where therapeutic transgenes can integrate and function without perturbing endogenous gene activity or promoting cancer.

Many different microRNAs (miRNAs) have now been linked to cancer, but our understanding of the pathways that are regulated by these miRNAsin vivois still limited. This Review discusses progress in using mouse models to understand the roles of miRNAs in cancer and the therapeutic potential of these molecules.

Obesity is increasing in the developed world, and epidemiological studies indicate that this is accompanied by an increased risk of cancer. This Opinion article discusses the possible mechanisms by which obesity might promote tumorigenesis.

Choline metabolism is commonly deregulated in cancer, leading to increased levels of choline metabolites. This Review discusses the deregulation of choline metabolism in cancer, its reciprocal interaction with oncogenic signalling and the possible clinical applications in diagnostics and therapy.

Although gastrointestinal stromal tumours (GISTs) are genetically heterogeneous, the identification of receptor tyrosine kinase mutations has led to improved treatments using targeted therapy. This Review discusses how the underlying genetics influences GIST disease progression and therapeutic responses, new insights into the cellular origins of GISTs and strategies for overcoming therapeutic resistance.

Cancer chemoprevention approaches generally use long-term, continuous treatment, which can lead to adverse events. This Opinion article discusses whether short-term, intermittent therapy that exploits synthetic lethal interactions in premalignant cells might reduce the toxicity of chemoprevention while retaining its benefits.

It was hoped that targeting protein prenylation would inhibit the oncogenic signalling of RAS family members. However, preclinical and clinical trials of prenyltransferase inhibitors have conflicting results. This Review discusses why these differences might occur and the future of targeting prenylation.

The US Food and Drug Administration (FDA) recently approved the immunotherapy agents sipuleucel-T and ipilimumab for the treatment of metastatic prostate cancer and melanoma, respectively. This Opinion article discusses how immunotherapy might be improved by understanding the mechanisms that are responsible for clinical benefit, identifying biomarkers that predict response or toxicity and developing combination therapies.

Epidemiological studies indicate that patients with Parkinson's disease seem to have a reduced risk of developing cancer (although exceptions exist). This Opinion article discusses the genes that are associated with Parkinson's disease and their possible roles in cancer biology.

The RAS oncogenes have far-reaching effects when they are oncogenically mutated. This Review discusses our current knowledge about the cell-autonomous and non-cell-autonomous effects of oncogenic RAS and how different RAS isoforms and substitutions seem to have different effects.

Several members of the tripartite motif (TRIM) proteins (one of the subfamilies of the RING type E3 ubiquitin ligases) seem to function as important regulators for carcinogenesis. This Review focuses on TRIM proteins that are involved in tumour development and progression.

Epigenetic alterations are leading candidates for the development of specific markers for cancer detection, diagnosis and prognosis, as well as new targets for cancer therapy. Which of the discoveries in the past 10 years are ready for advancement?

This Opinion article outlines nine major recommendations for improving our understanding of ovarian cancer and the outcomes of women with this group of diseases.

Will genomic and other systems level approaches help to overcome gaps in our understanding of metastasis?

Perineural invasion (PNI) is a prominent characteristic of pancreatic cancer that is involved in the generation of pain, and correlates with poor prognosis in most studies. This Review discusses the signalling molecules and pathways that are involved in PNI and whether knowledge of these could be used to alleviate pain and to reduce the incidence of PNI.