Thursday, December 1, 2011

Hot off the presses! Dec 01 Nat Rev Cancer

The Dec 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:

  • - Nat Rev Cancer 11(12):825 (2011)

  • - Nat Rev Cancer 11(12):827 (2011)
  • Lymphoma: Suppressive EPH-ect | PDF (219 KB)
    - Nat Rev Cancer 11(12):829 (2011)
    Follicular lymphoma, one of the most common non-Hodgkin's lymphomas, is characterized by a chromosomal translocation that increases the expression of the anti-apoptotic protein BCL-2, but additional events are required for lymphomagenesis. Hans-Guido Wendel and colleagues have further investigated the molecular pathogenesis of follicular lymphoma using functional genomics.
  • Epigenetics: Layer by layer | PDF (170 KB)
    - Nat Rev Cancer 11(12):830 (2011)
    The view that cancer is purely a genetic disease has taken a battering over recent years, perhaps most extensively from the recent discovery that between transcription and translation sits a whole host of regulatory RNAs, chiefly in the guise of microRNAs (miRNAs). Now, we can add yet another layer of regulation: the evidence from three papers that protein-coding and non-coding RNAs influence the interaction of miRNAs with their target RNAs.
  • Cancer stem cells: VEGF promotes stemness | PDF (189 KB)
    - Nat Rev Cancer 11(12):831 (2011)
    In addition to inducing angiogenesis, vascular endothelial growth factor (VEGF) signalling may directly affect tumour cells. Using a mouse model of chemically induced skin tumours, C ric Blanpain and colleagues have investigated the role of VEGF in cancer stem cells (CSCs).
  • Genetics: BRCA inequality | PDF (208 KB)
    - Nat Rev Cancer 11(12):831 (2011)
    There is a continued debate regarding the clinical predictive value of lesions in BRCA1 and BRCA2 in ovarian cancer. A new study suggests that BRCA1 and BRCA2 may have more divergent clinical relevance than was previously thought.
  • Senescence: NF-κB shows its beneficial side | PDF (258 KB)
    - Nat Rev Cancer 11(12):832 (2011)
    The nuclear factor-κB (NF-κB) transcription factor has long been linked with cancer, primarily through oncogenic functions that suppress apoptosis or that promote tumour growth and invasiveness. However, two new studies highlight the context dependence of NF-κB signalling by characterizing important tumour suppressive roles for NF-κB during senescence.
  • Therapeutics: Another tool in the BCR–ABL kit? | PDF (234 KB)
    - Nat Rev Cancer 11(12):832 (2011)
    Despite the success of treating chronic myelogenous leukaemia (CML) with the tyrosine kinase inhibitors (TKIs) imatinib, nilotinib and dasatinib, which inhibit the BCR–ABL fusion kinase, resistance and suboptimal responses in patients with advanced disease are still problematic. The ABL kinase contains an SH2 domain, which, in addition to mediating protein–protein interactions, facilitates the activation of the adjacent tyrosine kinase domain.
  • Kidney tumours: 'NRF said | PDF (196 KB)
    - Nat Rev Cancer 11(12):833 (2011)
    The tumour suppressor gene fumarate hydratase (FH) is just one of several genes to be implicated in the development of kidney tumours. Two papers published in Cancer Cell have identified a new pathway through which FH deficiency might promote tumour development.
  • Choline metabolism in malignant transformation
    - Nat Rev Cancer 11(12):835 (2011)
    Abnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, the modulation of enzymes that control anabolic and catabolic pathways causes increased levels of choline-containing precursors and breakdown products of membrane phospholipids. These increased levels are associated with proliferation, and recent studies emphasize the complex reciprocal interactions between oncogenic signalling and choline metabolism. Because choline-containing compounds are detected by non-invasive magnetic resonance spectroscopy (MRS), increased levels of these compounds provide a non-invasive biomarker of transformation, staging and response to therapy. Furthermore, enzymes of choline metabolism, such as choline kinase, present novel targets for image-guided cancer therapy.
  • MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy
    - Nat Rev Cancer 11(12):849 (2011)
    In normal cells multiple microRNAs (miRNAs) converge to maintain a proper balance of various processes, including proliferation, differentiation and cell death. miRNA dysregulation can have profound cellular consequences, especially because individual miRNAs can bind to and regulate multiple mRNAs. In cancer, the loss of tumour-suppressive miRNAs enhances the expression of target oncogenes, whereas increased expression of oncogenic miRNAs (known as oncomirs) can repress target tumour suppressor genes. This realization has resulted in a quest to understand the pathways that are regulated by these miRNAs using in vivo model systems, and to comprehend the feasibility of targeting oncogenic miRNAs and restoring tumour-suppressive miRNAs for cancer therapy. Here we discuss progress in using mouse models to understand the roles of miRNAs in cancer and the potential for manipulating miRNAs for cancer therapy as these molecules make their way towards clinical trials.
  • Gastrointestinal stromal tumours: origin and molecular oncology
    - Nat Rev Cancer 11(12):865 (2011)
    Gastrointestinal stromal tumours (GISTs) are a paradigm for the development of personalized treatment for cancer patients. The nearly simultaneous discovery of a biomarker that is reflective of their origin and the presence of gain-of-function kinase mutations in these tumours set the stage for more accurate diagnosis and the development of kinase inhibitor therapy. Subsequent studies of genotype and phenotype have led to a molecular classification of GIST and to treatment optimization on the basis of molecular subtype. The study of drug-resistant tumours has advanced our understanding of kinase biology, enabling the development of novel kinase inhibitors. Further improvements in GIST treatment may require targeting GIST stem cell populations and/or additional genomic events.
  • An intermittent approach for cancer chemoprevention
    - Nat Rev Cancer 11(12):879 (2011)
    Cancer chemoprevention approaches generally use long-term, continuous treatment, which can produce major preventive effects but which can also have unexpected serious adverse events. This raises the question of whether intermittent dosing schedules might reduce toxicity while retaining benefit, a concept that we call short-term intermittent therapy to eliminate premalignancy (SITEP). Recent preclinical studies support a novel SITEP approach whereby short-term, intermittent therapy eliminates premalignant cells via apoptosis that is induced by synthetic lethal interactions. Synthetic lethality allows personalized, selective elimination of premalignant clones without harming normal cells. This Opinion article provides a detailed discussion of the principle, method and future development of the SITEP approach.
  • Molecular mechanisms of cancer development in obesity
    - Nat Rev Cancer 11(12):886 (2011)
    The increasing incidence of obesity and its co-morbid conditions poses a great challenge to global health. In addition to cardiovascular disease and diabetes, epidemiological data demonstrate a link between obesity and multiple types of cancer. The molecular mechanisms underlying how obesity causes an increased risk of cancer are poorly understood. Obesity disrupts the dynamic role of the adipocyte in energy homeostasis, resulting in inflammation and alteration of adipokine (for example, leptin and adiponectin) signalling. Additionally, obesity causes secondary changes that are related to insulin signalling and lipid deregulation that may also foster cancer development. Understanding these molecular links may provide an avenue for preventive and therapeutic strategies to reduce cancer risk and mortality in an increasingly obese population.
  • Correspondence: The BIO-PIN paradigm: 'access to' or 'return of' results?
    - Nat Rev Cancer 11(12):895 (2011)
    With the increasing importance of biobank infrastructures for research, new ways to deal with personal data are being developed. The 'Bio-PIN' as proposed in the recent article by J.

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