Thursday, April 21, 2011

Hot off the presses! May 01 Nat Rev Cancer

The May 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(5):309 (2011)
  • Immunology: Bad company | PDF (196 KB)
    - Nat Rev Cancer 11(5):311 (2011)
    The presence or absence of different types of immune cells is known to influence outcome for cancer patients, but we are still some way from understanding the complex interaction between immune cell subsets and how they affect tumour growth and regression. A paper published in Cancer Discovery shows that the response of patients with breast cancer to specific chemotherapies is influenced by the subsets of leukocytes that are present in the tumour.
  • Tumour profiling: Multiple myeloma in the spotlight | PDF (225 KB)
    - Nat Rev Cancer 11(5):312 (2011)
    Identifying the acquired somatic mutations in a tumour is a powerful approach for elucidating the molecular mechanisms of cancer progression. A study recently published in Nature describes the full genome sequencing analysis of multiple myeloma, a cancer of mature B lymphoid cells.
  • Genomics: One cell at a time | PDF (263 KB)
    - Nat Rev Cancer 11(5):312 (2011)
    Genomic analyses of tumour samples can provide insight into tumour progression but they are complicated to interpret as such samples are genetically heterogeneous and can be comprised of various cell types. So, Michael Wigler and colleagues used single nucleus sequencing (SNS) of cells from two human breast cancers to investigate tumour progression.
  • Autophagy: Limiting factors | PDF (122 KB)
    - Nat Rev Cancer 11(5):313 (2011)
    NRAS, KRAS and HRAS are often deregulated in cancer; however, increased RAS activity does not guarantee tumour formation, as other pathways, such as cell death or senescence, limit the effects of oncogenic RAS. Three recent papers have indicated that autophagy is induced by oncogenic RAS and both limits and enables cellular survival.
  • Tumorigenesis: Neighbourhood watch | PDF (326 KB)
    - Nat Rev Cancer 11(5):314 (2011)
    Multiple observations suggest that host tissues possess intrinsic tumour-suppressive activity that can eliminate premalignant cells (a type of cell competition). However, the mechanisms by which this occurs are unknown.
  • Breast cancer: SRC hits the mark | PDF (214 KB)
    - Nat Rev Cancer 11(5):314 (2011)
    Trastuzumab (Herceptin; Genentech) is a therapeutic monoclonal antibody targeting ERBB2 (also known as HER2), a receptor tyrosine kinase (RTK) that is overexpressed in ~30% of breast cancers. Various molecular mechanisms of de novo and acquired resistance are major limitations of the clinical efficacy of this and other anticancer therapies.
  • Tumour microenvironment: Target practice | PDF (349 KB)
    - Nat Rev Cancer 11(5):315 (2011)
    The many adventures of MYC continue this month with a new publication by Laura Soucek, Gerard Evan and colleagues, which indicates that blocking the activity of endogenous LMYC, NMYC and MYC (collectively referred to as Myc) suppresses tumour development by eliciting effects both on tumour cells and on the tumour microenvironment.
  • Desmosomes: new perpetrators in tumour suppression
    - Nat Rev Cancer 11(5):317 (2011)
    Adherens junctions, which are intercellular adhesive complexes that are crucial for maintaining epithelial homeostasis, are downregulated in many cancers to promote tumour progression. However, the role of desmosomes — adhesion complexes that are related to adherens junctions — in carcinogenesis has remained elusive. Recent studies using mouse genetic approaches have uncovered a role for desmosomes in tumour suppression, demonstrating that desmosome downregulation occurs before that of adherens junctions to drive tumour development and early invasion, suggesting a two-step model of adhesion dysfunction in cancer progression.
  • Otto Warburg's contributions to current concepts of cancer metabolism
    - Nat Rev Cancer 11(5):325 (2011)
    Otto Warburg pioneered quantitative investigations of cancer cell metabolism, as well as photosynthesis and respiration. Warburg and co-workers showed in the 1920s that, under aerobic conditions, tumour tissues metabolize approximately tenfold more glucose to lactate in a given time than normal tissues, a phenomenon known as the Warburg effect. However, this increase in aerobic glycolysis in cancer cells is often erroneously thought to occur instead of mitochondrial respiration and has been misinterpreted as evidence for damage to respiration instead of damage to the regulation of glycolysis. In fact, many cancers exhibit the Warburg effect while retaining mitochondrial respiration. We re-examine Warburg's observations in relation to the current concepts of cancer metabolism as being intimately linked to alterations of mitochondrial DNA, oncogenes and tumour suppressors, and thus readily exploitable for cancer therapy.
  • Notch signalling in solid tumours: a little bit of everything but not all the time
    - Nat Rev Cancer 11(5):338 (2011)
    The discovery of Notch in Drosophila melanogaster nearly a century ago opened the door to an ever-widening understanding of cellular processes that are controlled or influenced by Notch signalling. As would be expected with such a pleiotropic pathway, the deregulation of Notch signalling leads to several pathological conditions, including cancer. A role for Notch is well established in haematological malignancies, and more recent studies have provided evidence for the importance of Notch activity in solid tumours. As it is thought to act as an oncogene in some cancers but as a tumour suppressor in others, the role of Notch in solid tumours seems to be highly context dependent.
  • Brain metastases as preventive and therapeutic targets
    - Nat Rev Cancer 11(5):352 (2011)
    The incidence of metastasis to the brain is apparently rising in cancer patients and threatens to limit the gains that have been made by new systemic treatments. The brain is considered a 'sanctuary site' as the blood–tumour barrier limits the ability of drugs to enter and kill tumour cells. Translational research examining metastasis to the brain needs to be multi-disciplinary, marrying advanced chemistry, blood–brain barrier pharmacokinetics, neurocognitive testing and radiation biology with metastasis biology, to develop and implement new clinical trial designs. Advances in the chemoprevention of brain metastases, the validation of tumour radiation sensitizers and the amelioration of cognitive deficits caused by whole-brain radiation therapy are discussed.
  • The calpain system and cancer
    - Nat Rev Cancer 11(5):364 (2011)
    The calpains are a conserved family of cysteine proteinases that catalyse the controlled proteolysis of many specific substrates. Calpain activity is implicated in several fundamental physiological processes, including cytoskeletal remodelling, cellular signalling, apoptosis and cell survival. Calpain expression is altered during tumorigenesis, and the proteolysis of numerous substrates, such as inhibitors of nuclear factor-κB (IκB), focal adhesion proteins (including, focal adhesion kinase and talin) and proto-oncogenes (for example, MYC), has been implicated in tumour pathogenesis. Recent evidence indicates that the increased expression of certain family members might influence the response to cancer therapies, providing justification for the development of novel calpain inhibitors.
  • An analogy between the evolution of drug resistance in bacterial communities and malignant tissues
    - Nat Rev Cancer 11(5):375 (2011)
    Cancer cells rapidly evolve drug resistance through somatic evolution and, in order to continue growth in the metastatic phase, violate the organism-wide consensus of regulated growth and beneficial communal interactions. We suggest that there is a fundamental mechanistic connection between the rapid evolution of resistance to chemotherapy in cellular communities within malignant tissues and the rapid evolution of antibiotic resistance in bacterial communities. We propose that this evolution is the result of a programmed and collective stress response performed by interacting cells, and that, given this fundamental connection, studying bacterial communities can provide deeper insights into the dynamics of adaptation and the evolution of cells within tumours.
  • Correspondence: The role of the tumour microenvironment in the biology of head and neck cancer: lessons from mobile tongue cancer
    - Nat Rev Cancer 11(5):382 (2011)
    We read with great interest the Review by Leemans and colleagues (The molecular biology of head and neck cancer. Nature Rev. Cancer11, 9–22 (2011)

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