Articles in 2009

The selective pressures for the retention of primordial p53 genes predated the appearance of cancer. Therefore, wild-type tumour suppressive functions were probably co-opted from unrelated primordial activities. Is it possible to deduce what these early functions might have been?

The Rb–E2f and MDM2–p53 pathways are both defective in most human tumours, indicating that these pathways function independently in the control of cell fate. However, extensive crosstalk between these two pathways also exists. How do they coordinately affect tumour biology?

Target response element sequences are a crucial part of the p53 network. This Review describes how functional response elements can be defined and discusses the implications of non-canonical p53 response elements, which greatly expand the universe of p53-regulated genes, on the part that p53 plays as a tumour suppressor.

When p53 was first discovered, it received relatively little attention from cancer researchers. The road leading to p53's rise to fame, and the recognition ofTP53as the most frequently altered gene in human cancer, has been long and winding. This Timeline examines the rich history of this pivotal tumour suppressor.

p53 is an evolutionarily ancient coordinator of metazoan stress responses and its role in tumour suppression is likely to be a relatively recent adaptation. This Review discusses how such evolutionary retooling of this venerable transcription factor entails compromises that restrict its efficacy as a tumour suppressor.

Understanding the activities of p53 in tumour suppression and in other processes has been substantially aided by the use of mouse models. How have these models evolved and what have they taught us about p53 and tumour suppression?

p53 can regulate numerous aspects of metabolic pathways and thereby influence the metabolic alterations exhibited by tumour cells. However, the contribution of p53 is complex and in some cases might promote, rather than inhibit, tumour progression. So, just what is p53 doing?

How important is the DNA damage response in mobilizing the tumour suppression function of p53? This Review considers how supporting and conflicting evidence about the role of DNA damage response signalling in cancer can be reconciled.

The efficacy of endocrine therapies (such as tamoxifen) in breast cancer is limited by intrinsic and acquired therapeutic resistance. What do we know about the genetic lesions and molecular processes that determine endocrine resistance in the clinic, and how can we use this to improve therapy?

The failure of three Phase III randomized trials that assessed the efficacy of anti-idiotype vaccines for the treatment of follicular lymphoma has raised many questions and controversies. In this article, Maurizio Bendandi expresses his thoughts on these findings and argues that new trials are necessary.

Recent work has indicated that the p160 SRC family of transcriptional co-activators are subject to amplification and overexpression in various human cancers. This Review discusses the molecular mechanisms responsible, along with the mechanisms by which SRCs promote breast and prostate cancer cell proliferation and survival.

How does therapeutic resistance affect disease relapse? Here the authors argue that the tumour microenvironment mediates a complex form ofde novodrug resistance and that adjuvant inhibition of key stromal factors could prevent the emergence of therapeutic resistance and relapse.

Death due to smoking — from cancer, vascular disease or tuberculosis — is growing worldwide, particularly in low- and middle-income countries, in which the prevalence of smoking is increasing. How many people could die from smoking before 2050 and how might this be avoided?

Mutant p53 proteins not only lose their tumour suppressive ability, but also gain new properties that promote tumorigenesis. What are these properties and what are the clinical implications?