Hot off the presses! Oct 01 Nat Rev Cancer

The Oct 01 issue of the Nat Rev Cancer is now up on Pubget (About Nat Rev Cancer): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• From the editors
  - Nat Rev Cancer 9(10):683 (2009)
  
• Tumorigenesis: No frills attached
  - Nat Rev Cancer 9(10):685 (2009)
  
• Therapeutics: One and one makes...
  - Nat Rev Cancer 9(10):686 (2009)
  
• Metabolism: Giving antioxidants a bad rap
  - Nat Rev Cancer 9(10):686 (2009)
  
• In brief: Signalling, Epigenetics, Diabetes, Non-coding RNAs
  - Nat Rev Cancer 9(10):687 (2009)
  
• Senescence: The more the merrier
  - Nat Rev Cancer 9(10):688 (2009)
  
• Chondrosarcoma: p53 and Gli combine forces
  - Nat Rev Cancer 9(10):688 (2009)
  
• Transcription: Reaching a consensus
  - Nat Rev Cancer 9(10):689 (2009)
  
• p53 and metabolism
  - Nat Rev Cancer 9(10):691-700 (2009)
  Although metabolic alterations have been observed in cancer for almost a century, only recently have the mechanisms underlying these changes been identified and the importance of metabolic transformation realized. p53 has been shown to respond to metabolic changes and to influence metabolic pathways through several mechanisms. The contributions of these activities to tumour suppression are complex and potentially rather surprising: some reflect the function of basal p53 levels that do not require overt activation and others might even promote, rather than inhibit, tumour progression.
• When mutants gain new powers: news from the mutant p53 field
  - Nat Rev Cancer 9(10):701-713 (2009)
  Ample data indicate that mutant p53 proteins not only lose their tumour suppressive functions, but also gain new abilities that promote tumorigenesis. Moreover, recent studies have modified our view of mutant p53 proteins, portraying them not as inert mutants, but rather as regulated proteins that influence the cancer cell transcriptome and phenotype. This influence is clinically manifested as association of TP53 mutations with poor prognosis and drug resistance in a growing array of malignancies. Here, we review recent studies on mutant p53 regulation, gain-of-function mechanisms, transcriptional effects and prognostic association, with a focus on the clinical implications of these findings.
• Tumour suppression by p53: a role for the DNA damage response?
  - Nat Rev Cancer 9(10):714-723 (2009)
  Loss of p53 function occurs during the development of most, if not all, tumour types. This paves the way for genomic instability, tumour-associated changes in metabolism, insensitivity to apoptotic signals, invasiveness and motility. However, the nature of the causal link between early tumorigenic events and the induction of the p53-mediated checkpoints that constitute a barrier to tumour progression remains uncertain. This Review considers the role of the DNA damage response, which is activated during the early stages of tumour development, in mobilizing the tumour suppression function of p53. The relationship between these events and oncogene-induced p53 activation through the ARF pathway is also discussed.
• The expanding universe of p53 targets
  - Nat Rev Cancer 9(10):724-737 (2009)
  The p53 tumour suppressor is modified through mutation or changes in expression in most cancers, leading to the altered regulation of hundreds of genes that are directly influenced by this sequence-specific transcription factor. Central to the p53 master regulatory network are the target response element (RE) sequences. The extent of p53 transactivation and transcriptional repression is influenced by many factors, including p53 levels, cofactors and the specific RE sequences, all of which contribute to the role that p53 has in the aetiology of cancer. This Review describes the identification and functionality of REs and highlights the inclusion of non-canonical REs that expand the universe of genes and regulation mechanisms in the p53 tumour suppressor network.
• p53 and E2f: partners in life and death
  - Nat Rev Cancer 9(10):738-748 (2009)
  During tumour development cells sustain mutations that disrupt normal mechanisms controlling proliferation. Remarkably, the Rb–E2f and MDM2–p53 pathways are both defective in most, if not all, human tumours, which underscores the crucial role of these pathways in regulating cell cycle progression and viability. A simple interpretation of the observation that both pathways are deregulated is that they function independently in the control of cell fate. However, a large body of evidence indicates that, in addition to their independent effects on cell fate, there is extensive crosstalk between these two pathways, and specifically between the transcription factors E2F1 and p53, which influences vital cellular decisions. This Review discusses the molecular mechanisms that underlie the intricate interactions between E2f and p53.
• The first 30 years of p53: growing ever more complex
  - Nat Rev Cancer 9(10):749-758 (2009)
  Thirty years ago p53 was discovered as a cellular partner of simian virus 40 large T-antigen, the oncoprotein of this tumour virus. The first decade of p53 research saw the cloning of p53 DNA and the realization that p53 is not an oncogene but a tumour suppressor that is very frequently mutated in human cancer. In the second decade of research, the function of p53 was uncovered: it is a transcription factor induced by stress, which can promote cell cycle arrest, apoptosis and senescence. In the third decade after its discovery new functions of this protein were revealed, including the regulation of metabolic pathways and cytokines that are required for embryo implantation. The fourth decade of research may see new p53-based drugs to treat cancer. What is next is anybody's guess.
• p53 ancestry: gazing through an evolutionary lens
  - Nat Rev Cancer 9(10):758-762 (2009)
  Evolutionary patterns indicate that primordial p53 genes predated the appearance of cancer. Therefore, wild-type tumour suppressive functions and mutant oncogenic functions that give celebrity status to this gene family were probably co-opted from unrelated primordial activities. Is it possible to deduce what these early functions might have been? And might this knowledge provide a platform for therapeutic opportunities?