Directly targeting transcriptional dysregulation in cancer - PubMed (original) (raw)

Review

. 2015 Nov;15(11):686-94.

doi: 10.1038/nrc4018.

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Review

Directly targeting transcriptional dysregulation in cancer

Thomas J Gonda et al. Nat Rev Cancer. 2015 Nov.

Abstract

Drugs that target intracellular signalling pathways have markedly improved progression-free survival of patients with cancers who were previously regarded as untreatable. However, the rapid emergence of therapeutic resistance, as a result of bypass signalling or downstream mutation within kinase-mediated signalling cascades, has curtailed the benefit gained from these therapies. Such resistance mechanisms are facilitated by the linearity and redundancy of kinase signalling pathways. We argue that, in each cancer, the dysregulation of key transcriptional regulators not only defines the cancer phenotype but is essential for its development and maintenance. Furthermore, we propose that, as therapeutic targets, these transcriptional regulators are less prone to bypass by alternative mutational events or clonal heterogeneity, and therefore we must rekindle our efforts to directly target transcriptional regulation across a broad range of cancers.

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