Review Articles in 2015

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.

Immunotherapy has undoubtedly become an effective treatment for many cancers, but how can we make the most of this approach? In this Review, Meleroet al. discuss how immune-targeted therapies can be synergistically combined to provide maximal benefit to patients.

Although most cancers exhibit some degree of intratumour heterogeneity, we are far from understanding the dynamics that operate among subclonal populations within tumours. This Review discusses the growing evidence that cooperative behaviour of tumour subclones can influence disease progression.

This Review discusses what we have learned about the biology of rhabdomyosarcoma using various model systems, and how these models might be used to discover new targetable pathogenic mechanisms.

'Cellular senescence' has been broadened to describe durable states of proliferative arrest induced by disparate stress factors. This Review discusses the limitations of senescence-associated biomarkers and provides suggestions for how to improve the phenotypic description of senescence.

In this Review, Barker and colleagues describe the mechanisms of radioresistance that are mediated by the tumour stroma and explore how these mechanisms can be targeted to improve radiotherapy responses.

Histone–lysineN-methyltransferase 2 (KMT2) family proteins, initially named the mixed lineage leukaemia (MLL) family, are altered in many types of cancers beyond MLL. Inhibitors of KMT2 function are being developed and could work as therapeutics in a variety of cancer types.