Nature Reviews Cancer 9, 849 (2009). doi:10.1038/nrc2733

Authors: Tracy A. Brooks & Laurence H. Hurley

MYC is deregulated in most tumour types, but an effective means to selectively target its aberrant expression is not yet available. Supercoiling that is induced by transcription has been demonstrated to have dynamic effects on DNA in the MYC promoter element: it converts duplex

Nature Reviews Cancer 9, 897 (2009). doi:10.1038/nrc2745

Author: Sharad Kumar

Aberrations in proteins that control apoptosis and cell survival are common in cancer. These aberrations often reside in signalling proteins that control the activation of the apoptotic machinery or in the Bcl-2 family of proteins that control caspase activation. Recent evidence suggests that caspase 2,

Nature Reviews Cancer 9, 886 (2009). doi:10.1038/nrc2747

Authors: Saurabh Sahar & Paolo Sassone-Corsi

Circadian rhythms govern a remarkable variety of metabolic and physiological functions. Accumulating epidemiological and genetic evidence indicates that the disruption of circadian rhythms might be directly linked to cancer. Intriguingly, several molecular gears constituting the clock machinery have been found to establish functional interplays with

Nature Reviews Cancer 9, 874 (2009). doi:10.1038/nrc2761

Author: Donald W. Kufe

Epithelia are protected from adverse conditions by a mucous barrier. The secreted and transmembrane mucins that constitute the mucous barrier are largely unrecognized as effectors of carcinogenesis. However, both types of mucins are intimately involved in inflammation and cancer. Moreover, diverse human malignancies overexpress transmembrane

Nature Reviews Cancer 9, 862 (2009). doi:10.1038/nrc2763

Authors: Christopher J. Brown, Sonia Lain, Chandra S. Verma, Alan R. Fersht & David P. Lane

Currently, around 11 million people are living with a tumour that contains an inactivating mutation of TP53 (the human gene that encodes p53) and another 11 million have tumours in which the p53 pathway is partially abrogated through the inactivation of other signalling or

Nature Reviews Cancer 9, 847 (2009). doi:10.1038/nrc2766

Author: Emily J. Chenette

Non-small-cell lung cancer (NSCLC) is a leading cause of cancer death worldwide. Small-molecule inhibitors that target epidermal growth factor receptor (EGFR) have shown some clinical success; however, mutations in KRAS, which are detected in 20–30% of NSCLC adenocarcinomas, render these therapeutics mostly

Nature Reviews Cancer 9, 846 (2009). doi:10.1038/nrc2767

Author: Iley Ozerlat

Regulation of cell motility is important for the metastatic dissemination of tumour cells from their primary location to lymph or blood vessels. Transforming growth factor-β (TGFβ) signalling — which is mediated by Smad transcription factors — enhances cell motility andtumour progression. Erik Sahai and colleagues

Nature Reviews Cancer 9, 846 (2009). doi:10.1038/nrc2768

Author: Nicola McCarthy

Not all cell types are amenable to transformation by the overexpression, deletion or deregulation of specific genes. Some cell types require multiple genetic and epigenetic changes before becoming tumorigenic, whereas others appear inert, irrespective of the genetic insult. Changes to the surrounding microenvironment can also

Nature Reviews Cancer 9, 845 (2009). doi:10.1038/nrc2769

Author: Sarah Seton-Rogers

Although it is generally accepted that the tumour microenvironment influences tumour formation and progression, how stromal cells communicate with epithelial tumour cells is not well understood. Gustavo Leone, Michael Ostrowski and colleagues have now shown that PTEN in stromal cells provides an important tumour

Nature Reviews Cancer 9, 843 (2009). doi:10.1038/nrc2770

We end this year contemplating what history can teach us, with a particular focus on transcription factors and anticancer drug development. This issue comes with a Poster that highlights some of the key discoveries from the past 30 years of p53 research and how these