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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.
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.
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.
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.
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.
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.
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.
