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:

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  - Nat Rev Cancer 11(10):687 (2011)
  
• Epithelial to mesenchymal transition: Layers of regulation | PDF (259 KB)
  - Nat Rev Cancer 11(10):689 (2011)
  Epithelial to mesenchymal transition (EMT), which can enhance the migration and invasion of cancer cells, is known to be regulated transcriptionally, but less is known about other mechanisms that regulate this process. Two recent papers have shown that EMT can be driven by both alternative splicing and chromatin modification.
• Cell migration: Cytokine cues | PDF (208 KB)
  - Nat Rev Cancer 11(10):690 (2011)
  The generation of contractile forces in both tumour cells and the surrounding stromal cells is necessary to create a permissive environment for cancer cell migration and metastasis, but the signals controlling actomyosin contractility are not well understood. Chris Marshall's laboratory working on melanoma cell migration and Cedric Gaggioli's laboratory working on carcinoma-associated fibroblasts (CAFs) in squamous cell carcinoma have shown that a cytokine signalling pathway activating the kinase JAK1 is important in both cell types.
• Ancient dog with new trick? | PDF (74 KB)
  - Nat Rev Cancer 11(10):690 (2011)
  Colchicine, which was first described as a mitotic poison, looks set to make a return to the forefront of cancer research, albeit in disguise as a 'cloaked' vascular-disrupting agent.
• Tumour heterogeneity: That's the theory | PDF (349 KB)
  - Nat Rev Cancer 11(10):691 (2011)
  A new model published as a Theory paper in Cell indicates that breast cancer cells with a stem cell phenotype can arise from differentiated luminal or basal cells to re-establish phenotypic equilibrium within a cell population.
• Genomic instability: Aneuploidy stokes the fire | PDF (413 KB)
  - Nat Rev Cancer 11(10):692 (2011)
  There is considerable debate about whether aneuploidy (irregular numbers of individual chromosomes) is a cause or merely a consequence of the interlinked phenomena of genomic instability and tumorigenesis: two new reports provide further evidence for a causal role for aneuploidy in both.
• Metabolism: Haem is where the heart is | PDF (448 KB)
  - Nat Rev Cancer 11(10):692 (2011)
  Fumarate hydratase (FH), an enzyme in the tricarboxylic acid (TCA) cycle, is mutated in the germline of patients with hereditary leiomyomatosis and renal cell cancer (HLRCC). This mutation results in a non-functional TCA cycle, but kidney cells with this mutation can form aggressive tumours.
• Therapy: Targeting MYC? You BET | PDF (217 KB)
  - Nat Rev Cancer 11(10):693 (2011)
  Targeting the oncogenic effects of MYC could have wide application to treat cancer patients, but so far drug development has proved challenging. Bradner, Mitsiades and colleagues approached this problem by targeting MYC-mediated chromatin modifications.
• Perineural invasion and associated pain in pancreatic cancer
  - Nat Rev Cancer 11(10):695 (2011)
  Perineural invasion (PNI) is a prominent characteristic of pancreatic cancer. PNI is a process whereby cancer cells invade the surrounding nerves, thus providing an alternative route for metastatic spread and pain generation. PNI is thought to be an indicator of aggressive tumour behaviour and has been shown to correlate with poor prognosis of patients with pancreatic cancer. Recent studies demonstrated that some signalling molecules and pathways that are involved in PNI are also involved in pain generation. Targeting these signalling pathways has shown some promise in alleviating pain and reducing PNI, which could potentially improve treatment outcomes for patients with pancreatic cancer.
• Aminoacyl-tRNA synthetases and tumorigenesis: more than housekeeping
  - Nat Rev Cancer 11(10):708 (2011)
  Over the past decade, the identification of cancer-associated factors has been a subject of primary interest not only for understanding the basic mechanisms of tumorigenesis but also for discovering the associated therapeutic targets. However, aminoacyl-tRNA synthetases (ARSs) have been overlooked, mostly because many assumed that they were simply 'housekeepers' that were involved in protein synthesis. Mammalian ARSs have evolved many additional domains that are not necessarily linked to their catalytic activities. With these domains, they interact with diverse regulatory factors. In addition, the expression of some ARSs is dynamically changed depending on various cellular types and stresses. This Analysis article addresses the potential pathophysiological implications of ARSs in tumorigenesis.
• Rethinking ovarian cancer: recommendations for improving outcomes
  - Nat Rev Cancer 11(10):719 (2011)
  There have been major advances in our understanding of the cellular and molecular biology of the human malignancies that are collectively referred to as ovarian cancer. At a recent Helene Harris Memorial Trust meeting, an international group of researchers considered actions that should be taken to improve the outcome for women with ovarian cancer. Nine major recommendations are outlined in this Opinion article.
• A decade of exploring the cancer epigenome — biological and translational implications
  - Nat Rev Cancer 11(10):726 (2011)
  The past decade has highlighted the central role of epigenetic processes in cancer causation, progression and treatment. Next-generation sequencing is providing a window for visualizing the human epigenome and how it is altered in cancer. This view provides many surprises, including linking epigenetic abnormalities to mutations in genes that control DNA methylation, the packaging and the function of DNA in chromatin, and metabolism. Epigenetic alterations are leading candidates for the development of specific markers for cancer detection, diagnosis and prognosis. The enzymatic processes that control the epigenome present new opportunities for deriving therapeutic strategies designed to reverse transcriptional abnormalities that are inherent to the cancer epigenome.
• Unravelling the complexity of metastasis — molecular understanding and targeted therapies
  - Nat Rev Cancer 11(10):735 (2011)
  Despite recognizing the devastating consequences of metastasis, we are not yet able to effectively treat cancer that has spread to vital organs. The inherent complexity of genomic alterations in late-stage cancers, coupled with numerous heterotypic interactions that occur between tumour and stromal cells, represent fundamental challenges in our quest to understand and control metastatic disease. The incorporation of genomic and other systems level approaches, as well as technological breakthroughs in imaging and animal modelling, have galvanized the effort to overcome gaps in our understanding of metastasis. Future research carries with it the potential to translate the wealth of new knowledge and conceptual advances into effective targeted therapies.
• Cancer research: past, present and future
  - Nat Rev Cancer 11(10):749 (2011)
  Research into cancer over the past 10 years has diverged enormously, partly based on the large number of new technologies that are now at our finger tips. With areas of cancer research so disparate, it is not always easy to identify where the next new findings and therapies might come from. With this in mind, we asked four leading cancer researchers from around the world what, in their opinion, we have learnt over the past 10 years and how we should progress in the next 10 years.