Reviews & Analysis

The zebrafish has emerged as an important model system with which to investigate cancer, particularly for validating genomics data and for undertaking screens for oncogenes and drivers of tumour progression and metastasis. This Review outlines what we have learned and could still learn from cancer research using the zebrafish.

Many therapeutic agents target the ERBB family of receptor tyrosine kinases in various cancers. This Opinion article describes our latest understanding of the value of combining inhibitors directed towards an individual ERBB family member, including the molecular mechanisms of synergy and progress in clinical trials.

The efficacy of surgery is dependent on removing the entire tumour and also on not damaging important structures, such as nerves. Strategies, such as fluorescent labelling, are being developed to visually identify tumour cells and crucial structures in order to improve the safe resection of tumours. These methods have the potential to improve the survival of cancer patients, as discussed here.

Endothelin 1 (ET1) is a secreted protein that can function through autocrine and paracrine signalling to modulate various properties of cancer cells and their microenvironment. This Review describes our latest understanding of the biological roles of ET1 in cancer and the results of clinical trials with drugs that target the ET1 signalling pathway.

Adoptive T cell therapy using engineered T cells to improve antitumour responses is showing promise for the treatment of haematological malignancies in particular. This Review discusses the strategies to engineer T cells and the progress that has been made with using gene-modified T cells to treat cancer patients.

Can novel materials, probes and tools, which represent an integration of traditional and new engineering approaches with cancer biology, help us to better understand tumour progression and invasion?

The DREAM complex provides a previously unsuspected unifying role in the cell cycle. This Opinion article explores the functions of the DREAM complex and how they might contribute to tumour development and progression.

Several cancers and genetic disorders are linked to defects in helicases that have roles in genome maintenance and stability. This Review discusses helicase-dependent DNA repair pathways and how targeting these might improve cancer treatments based on DNA-damaging chemotherapy or radiation.

Although the ABL1 kinase is well known as the fusion partner with BCR in chronic myeloid leukaemia (CML), roles for the ABL family (ABL1 and ABL2) in solid tumours are beginning to be uncovered. Small-molecule ABL inhibitors are crucial in CML therapy, but can these kinases be targeted for therapeutic benefit in other cancer types?

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.

In this Perspective article, the authors propose that the construction of a 'precancer niche' is a necessary and early step that is required for tumorigenesis. Because a cancer niche would evolve with the transformed cell, cancer niches potentially represent an emergent property of a tumour that could be a robust target for cancer prevention and therapy.

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.

Feinberg and Timp review cancer-associated epigenetic alterations and propose that epigenetic dysregulation is an initiating force in tumorigenesis that promotes the selection of cancer-associated phenotypes and that can cooperate with genetic alterations, indicating that the gene-centric view of cancer biology is not the whole story.

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 domestic laying hen is the only non-human animal that spontaneously develops ovarian cancer with a high prevalence. This Opinion article discusses how the hen may be used as a potential model of human ovarian cancer, and the advantages and disadvantages of this system.

Allosteric disulphide bonds regulate the function of the mature proteins in which they reside. This Opinion article discusses the progress in our ability to identify and disrupt allosteric disulphide bonds and the potential therapeutic value of targeting these bonds in cancer.