Review Articles

Tumour metastasis is a major contributor to the mortality of cancer patients, so why is this phase of cancer pathogenesis not routinely targeted? This Review discusses the possible strategies — including preclinical research, combination therapies and clinical trial designs — that could be developed to target metastasis.

This Review discusses technological and biologically based advances in radiotherapy. The authors envisage that these two major strategies will act synergistically to further widen the therapeutic window of radiation oncology in the era of precision medicine.

This Review summarizes immune evasion mechanisms that limit the therapeutic efficacy of cancer vaccines. The authors discuss how improving vaccine design and using vaccines in combination with other anticancer therapies can boost treatment efficacy in patients with established cancers.

This Review discusses the molecular biology underlying chronic lymphocytic leukaemia (CLL). Emphasizing the role of genetic lesions in CLL initiation and clinical progression, the article also considers the clinical implications of these findings.

Interferons (IFNs) activate and regulate antitumour immune responses. This Review discusses lessons that can be learnt from using type I IFNs in oncology and our current understanding of the interferome in modifying antitumour immune responses.

Recent studies have shown that germline and somatic mutations in the proofreading exonuclease domains of the replicative DNA polymerases Pol δ and Pol ε are associated with several cancers. This Review summarizes what these mutations are and how they might drive tumorigenesis, and highlights their potential as novel biomarkers and therapeutic targets.

This Review discusses the role of natural killer (NK) cells in immunosurveillance of tumour cells, highlighting the new therapeutic approaches to NK cell targeting in the treatment of cancer and improvement of NK cell-mediated antitumour immune responses.

Understanding how DNA damage determines cell fate — DNA repair and cell survival or death — is important for gaining insight into carcinogenesis and in promoting successful cancer therapy. This Review describes key decision-making nodes in the complex interplay between DNA damage responses and cell fate signalling.

Increased activity and aberrant localization of cysteine cathepsin proteases within the tumour microenvironment have potent roles in driving cancer progression. This Review discusses the roles of cathepsins and provides a roadmap for the rational integration of cathepsin-targeting agents into clinical treatment.

This Review discusses mathematical modelling approaches in cancer research. These models can complement experimental and clinical studies, but can also challenge current paradigms, redefine our understanding of mechanisms driving tumorigenesis and shape future research.

This Review highlights emerging mechanisms of acquired resistance to agents targeting the androgen receptor in castration-resistant prostate cancer, which fall into the three broad categories of restored androgen receptor (AR) signalling, AR bypass signalling and complete AR independence.

Liver tumorigenesis is complex and depends on the cellular origin of a tumour as well as on environmental influences. This Review discusses the origins of various primary liver cancers, integrating our current understanding of cells of origin, liver tumour genomics and the disrupted hepatic microenvironment.

This Review discusses recent advances that shed new light on the relationship between centrosomes and cancer, raising the possibility that centrosome aberrations contribute to this disease in different ways than initially envisaged.

MEK1 and MEK2 have key roles in tumorigenesis and, therefore, represent promising targets for cancer therapy. This Review discusses the mechanisms of action of different inhibitors of MEK1 and MEK2, the mechanisms of resistance to these inhibitors and their current clinical progress.

The transcription factor MYC upregulates and downregulates distinct sets of target genes, promoting cell growth and proliferation, increased metabolic rate and RNA biogenesis. This Review discusses MYC-mediated transcriptional regulation in normal growth control, as well as in tumour development and maintenance.

This Review discusses the roles of members of the sirtuin (SIRT) family in cancer biology, which have dichotomous, context-dependent functions as tumour suppressors and oncogenes. Furthermore, the authors discuss the possibility of targeting the sirtuins for anticancer therapy.

This Review discusses nucleotide metabolism and how fluctuations in deoxyribonucleoside triphosphate (dNTP) pools affect genomic instability. Drugs that target this system have been in use for many years and some of these are discussed, as well as newer approaches to manipulating deoxyribonucleotide metabolism for cancer treatment.

This Review discusses the importance of glycobiology in cancer research, given its role in cancer development and progression, and provides an overview of possible targets for diagnostic application and therapeutic strategies.

Cancer cells exhibit huge phenotypic plasticity, which can lead to adaptations to the tumour microenvironment and therapy. Much of this plasticity seems to be encoded in signal transduction networks, such that alterations in signalling dynamics can affect many cancer-associated phenotypes and therapeutic response.

Obesity is associated with increased (and occasionally decreased) risk of developing several types of cancer. This Review discusses the epidemiological evidence available for, and the possible mechanisms that might lead to, this altered risk.