Review Articles

This Review discusses recent studies that offer quantitative insights into the dynamics of intestinal stem cell behaviour that govern homeostasis. These studies provide the necessary baseline parameters such that we can begin to understand stem cell behaviour during colorectal cancer development.

There is a clinical need for biomarkers to identify women with progressive cervical intraepithelial neoplasia (CIN) lesions to tailor clinical management and prevent overtreatment. This Review discusses the advances in understanding genetic and epigenetic alterations that underlie cervical cancer development, which offer opportunities for the molecular distinction of cervical cancer precursor lesions.

This Review highlights how intravital microscopy techniques have been used in living animals (predominantly mice) to unravel fundamental and dynamic aspects of several processes that are crucial for the initiation and progression of tumours, and it discusses future perspectives for these techniques.

Combined analyses of molecular data, such as DNA copy-number alteration, mRNA and protein expression, point to biological functions and molecular pathways being deregulated in multiple cancers. The integrative genomics methodologies that are used to interpret these data can seem daunting, but are discussed in this Review in simplistic terms and in the context of their use in cancer research.

Conway and colleagues provide a comprehensive overview of imaging techniques as pertaining to their use in identifying new drugs for cancer therapy.

The family of insulin-like growth factor (IGF) binding proteins (IGFBPs) have many actions beyond their endocrine role in IGF transport. IGFBPs regulate cell growth and survival, gene transcription, induction of apoptosis and DNA damage repair. These findings point to the intimate involvement of IGFBPs in tumour development, progression and resistance to treatment.

Although epidemiological and early clinical trials are inconsistent, and randomized control trials in humans do not yet exist to conclusively support a beneficial role for vitamin D, this Review assesses the evidence that vitamin D is important in cancer prevention.

F-box proteins, which are the substrate-recognition subunits of SKP1–cullin 1–F-box protein (SCF) E3 ubiquitin ligase complexes, have pivotal roles in multiple cellular processes. This Review discusses how dysregulation of F-box protein-mediated proteolysis contributes to tumorigenesis.

Bruton's tyrosine kinase (BTK) is important in B cell receptor (BCR) signalling, and so BTK is altered in many types of B cell-derived malignancy. This Review discusses the molecular biology of BTK, its involvement in the pathogenesis of B cell malignancies and the current efforts to therapeutically target it.

The glucose-regulated proteins (GRPs) are stress-inducible chaperones that mostly reside in the endoplasmic reticulum or the mitochondria. Recent advances have shown that the GRPs are involved in the regulation of cell signalling, proliferation, invasion, apoptosis, inflammation and immunity. Agents that target the GRPs are being developed as potential cancer therapies.

This Review describes some of the latest techniques that are being used to discover modulators of protein–protein interactions and how current drug discovery approaches have been adapted to successfully target these interfaces.

RET is a single-pass transmembrane receptor tyrosine kinase (RTK) that is required for normal development, maturation and maintenance of several tissues and cell types. This Review focuses on our understanding of RET biology and function in cancer, and it highlights recent advances that have suggested a broader role for RET in oncogenesis.

The past decade has been exciting in terms of research into the molecular and cellular biology of lymphatic vessels in cancer. This Review discusses the specific roles of distinct lymphatic vessel subtypes in cancer, and the potential diagnostic and therapeutic opportunities.

The latest large-scale genomic and epigenomic profiling studies have yielded an unprecedented abundance of novel data and provided deeper insights into gliomagenesis across all age groups. These studies have highlighted key distinctions, but also some commonalities, which are discussed in this Review.

Patricia L. M. Dahia gives an overview of insights learned from the study of pheochromocytomas and paragangliomas, which carry the highest degree of heritability of all human tumours.

Inhibitor of DNA binding (ID) proteins are transcriptional regulators that control the timing of cell fate determination and differentiation in stem and progenitor cells. The ability of ID proteins to function as central 'hubs' for the coordination of multiple cancer hallmarks is establishing them as therapeutic targets and biomarkers in specific types of human tumours.

p21-activated kinases (PAKs) have important roles in several oncogenic signalling pathways. How are PAKs activated in cancer, what are their key substrates, and how might small molecules against these enzymes best be developed and deployed for the treatment of cancer?

This Review discusses the elucidation of mechanisms whereby oestrogen drives both oestrogen receptor-α transactivation and receptor proteolysis, which might have important therapeutic implications not only for breast cancer but also for other hormone-regulated cancers.

This Review discusses recent evidence, particularly from mouse models, showing that some tetraspanin proteins have important roles in tumour initiation, promotion, metastasis and angiogenesis, and that they might therefore be valid therapeutic targets.

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.