Review Articles in 2013

This Review reminds us of all those pathways we longed to forget from first year biochemistry: deregulated one-carbon metabolism is a possible driver of oncogenesis. Given the wealth of clinically available agents that target one-carbon metabolism are there opportunities for translation into precision cancer medicine?

Forkhead box (FOX) transcription factors fine-tune the spatial and temporal expression of many genes and integrate a multitude of cellular and environmental signals. Several FOX family transcription factors have been implicated in cancer and may be therapeutic targets or putative biomarkers.

This Review outlines evidence supporting a role for macrophage-stimulating protein (MSP) and its receptor RON in cancer progression and discusses the therapeutic potential of targeting this signalling axis.

Cancer cells are subject to many apoptotic stimuli that would kill them were it not for compensatory prosurvival alterations. BCL-2-like (BCL-2L) proteins contribute to such aberrant behaviour. Targeting these proteins is not a new idea, but might still offer therapeutic efficacy if the phenotype of BCL-2L protein dependence is better understood and can be diagnosed by relevant biomarkers.

Sequencing approaches have confirmed that numerous, non-clonal translocations are a typical feature of cancer cells. The factors and pathways that promote translocations are becoming clearer, with non-homologous end-joining being implicated as a major source of chromosome rearrangements.

Awareness is increasing that progesterone signalling via the progesterone receptor (PR) has important roles in breast biology and breast cancer. Understanding more about this pathway may lead to new therapeutic and preventive options for breast cancer.

Over the past decade, our understanding of neuroblastoma has advanced tremendously. This Review discusses the key discoveries in the developmental biology, molecular genetics and immunology of neuroblastoma, as well as new translational tools to bring these promising scientific advances into the clinic.

The transforming growth factor-β (TGFβ) ligands have important functions in cancer. However, it is now becoming apparent that many of the other TGFβ superfamily members (bone morphogenetic proteins (BMPs), activins, NODAL, and growth and differentiation factors (GDFs)) have crucial roles in tumorigenesis and metastasis; these are the focus of this Review.

Increasing evidence indicates that components of the RNA polymerase complexes are altered in cancer. This Review discusses how all three classes of human RNA polymerase activity are dysregulated in cancer and the opportunities to therapeutically target RNA polymerase activity.

The regulation of iron metabolism is altered in tumour cells. Changes in iron regulation enhance iron influx and retention. This leads to altered cellular processes that foster cancer growth and metastasis, and provides an opportunity for the development of therapeutics that target iron availability.

For more than four decades, cells have been studied in space. This work has provided insight into how normal cells and cancer cells grow and aggregate into complex architectures and respond to extrinsic forces. This Review discusses what we have learned about cell biology from space-based research and how this might be applied to cancer research on Earth.

Pigment epithelium-derived factor (PEDF) has anti-angiogenic, antitumorigenic and antimetastatic properties. If PEDF is to be used for cancer management, a deeper appreciation of its many functions and mechanisms of action is needed, as discussed in this Review.

The presence of chronic obstructive pulmonary disease (COPD) is linked to an increased risk of developing lung cancer, independently of cigarette smoking dosage. This Review discusses the nature of the link between the two diseases and considers specific mechanisms that operate in both COPD and lung cancer.

A wealth of recent studies has characterized roles for the Hippo pathway in diverse cancer-relevant processes. This Review discusses our latest understanding of Hippo pathway signalling in cancer, including mechanisms of pathway disruption in cancer, and the opportunities and challenges for therapeutic intervention.

There have been substantial advances in understanding the molecular pathogenesis of thyroid cancer, which have provided insights into genetic and epigenetic alterations in this cancer and into PI3K and MAPK signalling, for example. This Review discusses these findings and the implications for novel treatment of thyroid cancer.

This Review discusses how genetic lineage tracing can be used to quantify the behaviour of normal, preneoplastic and tumour cells in epithelia in transgenic mice. It also discusses some of the limitations of lineage tracing in mouse models of cancer.

Drosophila melanogasterhas often provided the first glimpse into the mechanism of action of human cancer-related proteins. In addition,D. melanogasterstrains engineered to recapitulate key aspects of specific types of human cancer are providing us with further insights into malignancy, and serving as platforms for drug discovery.

Epithelial to mesenchymal transition (EMT) is essential for driving plasticity during development, but can also occur in tumour cells during cancer progression. This Review discusses the layers of regulation (including the transcriptional and translational machinery, non-coding RNAs, alternative splicing and protein stability) that control the process and plasticity of EMT.

Hepatocellular carcinoma (HCC) is mainly associated with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections. This Review outlines pathogenic mechanisms that seem to be common to both HBV and HCV, in the hope that this might suggest innovative approaches for the prevention and treatment of HCC.

LIM-domain-only (LMO) proteins are a subset of the LIM-domain protein family and function primarily as transcriptional regulators. They are associated with various cancers, including T cell acute lymphoblastic leukaemia (T-ALL) that resulted from unintended activation ofLMO2by insertional mutagenesis in human gene therapy trials. This Review discusses the roles and potential mechanisms of LMO proteins in cancer and the potential for therapeutic targeting.