Articles in 2013

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?

Seluanov, Gorbunova and colleagues find that high-molecular-mass hyaluronan — a component of the extracellular matrix — activates early contact inhibition, which suppresses tumorigenesis in naked mole rats.

Data recently published by Karen Vousden and colleagues indicate that TIGAR aids tumour development in the intestine.

A secreted translational variant of PTEN (PTEN-Long) can be taken up by neighbouring cells, where it can inhibit PI3K signalling, and administration of purified PTEN-Long to tumour-bearing mice induces tumour regression.

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?

A new drug shows promise for patients with triple-negative breast cancer.

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.

Two new studies emphasize links between metabolism and the epigenome by showing that various cancers with mutations in the Krebs cycle enzyme succinate dehydrogenase have a characteristic DNA hypermethylation phenotype.

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.

Macropinocytosis by RAS-mutant cells and tumours can supply cells with amino acids that can then be used in metabolic pathways.