Hot off the presses! Nov 01 Nat Rev Cancer

The Nov 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 10(11):735 (2010)
  
• Chromosomal instability: Coping with extra copies | PDF (390 KB)
  - Nat Rev Cancer 10(11):737 (2010)
  Aneuploidy — an abnormal number of chromosomes — has severe consequences for an organism and is associated with developmental abnormalities and cell death. Despite these disadvantages, cancer cells are frequently aneuploid and have a high proliferative capacity, suggesting that they implement mechanisms to allow them to survive the aneuploid state.
• Tumorigenesis: Joining the RANKs | PDF (277 KB)
  - Nat Rev Cancer 10(11):738 (2010)
  Receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) and its receptor RANK are better known for their role in the development and activation of osteoclasts and breast cancer metastasis to the bone. However, RANKL and RANK are also expressed in primary breast tumours and can induce proliferation in mammary epithelial cells (MECs), particularly in response to progesterone.
• Signalling: The calcium connection | PDF (237 KB)
  - Nat Rev Cancer 10(11):738 (2010)
  Changes in the cytosolic concentrations of Ca2+ can induce signalling pathways that regulate a broad range of cellular events, including those important in tumorigenesis. A recent study has characterized a new mechanism of constitutive Ca2+ signalling that involves the Ca2+ store-operated channel ORAI1 and ATP-powered calcium pumps.
• Tumour suppression: Ejector seat | PDF (227 KB)
  - Nat Rev Cancer 10(11):739 (2010)
  Exosomes are small vesicles that are secreted by various cells under certain conditions. They have recently gained prominence in cancer research owing to their capacity to carry mRNAs, microRNAs, and pro-oncogenic and pro-angiogenic proteins and deliver them to surrounding cells.
• Epigenetics: Demethylation links cell fate and cancer | PDF (257 KB)
  - Nat Rev Cancer 10(11):740 (2010)
  Genome-wide loss of DNA methylation is characteristic of many cancers; however, mutations in DNA methyltransferases (DNMTs) have not been linked with human tumours, so it has been unclear how this hypomethylation arises. New insights have been provided by a study in zebrafish showing that a tumour suppressor acts through a demethylase system to regulate cell fate decisions, and that loss of the normal control of demethylation contributes to tumorigenesis.
• Metabolism: Less is sometimes more | PDF (192 KB)
  - Nat Rev Cancer 10(11):740 (2010)
  In 1924, Otto Warburg noticed changes in the way cancer cells metabolized glucose compared with the metabolism of their healthy counterparts. Not only did they show increased glucose uptake, but they also used less glucose for oxidative phosphorylation, opting instead for fermentation.
• Improved chemotherapies | PDF (162 KB)
  - Nat Rev Cancer 10(11):740 (2010)
  Neuroblastoma is characterized by poor long-term survival as tumours normally relapse and disseminate after chemotherapy in more than 50% of the patients. A system of risk stratification established for this heterogeneous disease has helped to tailor chemotherapy to minimize therapeutic side effects, which can severely affect quality of life, and improve outcome.
• Tumour suppression | Invasion | Tumorigenesis | Oncogenes | PDF (161 KB)
  - Nat Rev Cancer 10(11):741 (2010)
  Glioma oncoprotein Bcl2L12 inhibits the p53 tumor suppressor Stegh, A. H.et al. Genes Dev. 24, 2194–2204 (2010)
• Immunology: In need of a boost? | PDF (232 KB)
  - Nat Rev Cancer 10(11):742 (2010)
  The inhibitor of apoptosis (IAP) proteins are involved in the induction of tumour cell survival, making them important new anticancer drug targets. IAPs are also implicated in the modulation of the adaptive and innate immune responses, and Glenn Dranoff, Michael Dougan and colleagues have found that the inhibition of IAPs increases T cell activation.
• Stem cells: Out for the count | PDF (218 KB)
  - Nat Rev Cancer 10(11):742 (2010)
  As more methods are published on how to generate induced pluripotent stem (iPS) cells from differentiated, mature cells, so increases the need to carefully analyse the DNA content of these cells. A recent paper published in Cell Stem Cell indicates that chromosomal aberrations in human iPS cells are more common than previously thought.
• Genetics: Partners in crime | PDF (166 KB)
  - Nat Rev Cancer 10(11):743 (2010)
  Over the past few years, genome-wide association studies (GWAS) have been useful in identifying genetic variations that are associated with risk for several types of cancer. Three GWAS recently reported in the same issue of Nature Genetics identify several new susceptibility loci for breast and ovarian cancer.
• The renin–angiotensin system and cancer: old dog, new tricks
  - Nat Rev Cancer 10(11):745 (2010)
  For cancers to develop, sustain and spread, the appropriation of key homeostatic physiological systems that influence cell growth, migration and death, as well as inflammation and the expansion of vascular networks are required. There is accumulating molecular and in vivo evidence to indicate that the expression and actions of the renin–angiotensin system (RAS) influence malignancy and also predict that RAS inhibitors, which are currently used to treat hypertension and cardiovascular disease, might augment cancer therapies. To appreciate this potential hegemony of the RAS in cancer, an expanded comprehension of the cellular actions of this system is needed, as well as a greater focus on translational and in vivo research.
• Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer
  - Nat Rev Cancer 10(11):760 (2010)
  Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) was first recognized in 2004 as a distinct, clinically relevant molecular subset of lung cancer. The disease has been the subject of intensive research at both the basic scientific and clinical levels, becoming a paradigm for how to understand and treat oncogene-driven carcinomas. Although patients with EGFR-mutant tumours have increased sensitivity to tyrosine kinase inhibitors (TKIs), primary and acquired resistance to these agents remains a major clinical problem. This Review summarizes recent developments aimed at treating and ultimately curing the disease.
• Acute promyelocytic leukaemia: novel insights into the mechanisms of cure
  - Nat Rev Cancer 10(11):775 (2010)
  The fusion oncogene, promyelocytic leukaemia (PML)–retinoic acid receptor-α (RARA), initiates acute promyelocytic leukaemia (APL) through both a block to differentiation and increased self-renewal of leukaemic progenitor cells. The current standard of care is retinoic acid (RA) and chemotherapy, but arsenic trioxide also cures many patients with APL, and an RA plus arsenic trioxide combination cures most patients. This Review discusses the recent evidence that reveals surprising new insights into how RA and arsenic trioxide cure this leukaemia, by targeting PML–RARα for degradation. Drug-triggered oncoprotein degradation may be a strategy that is applicable to many cancers.
• Engineering the perfect (bacterial) cancer therapy
  - Nat Rev Cancer 10(11):785 (2010)
  Bacterial therapies possess many unique mechanisms for treating cancer that are unachievable with standard methods. Bacteria can specifically target tumours, actively penetrate tissue, are easily detected and can controllably induce cytotoxicity. Over the past decade, Salmonella, Clostridium and other genera have been shown to control tumour growth and promote survival in animal models. In this Innovation article I propose that synthetic biology techniques can be used to solve many of the key challenges that are associated with bacterial therapies, such as toxicity, stability and efficiency, and can be used to tune their beneficial features, allowing the engineering of 'perfect' cancer therapies.
• Walls around tumours — why plants do not develop cancer
  - Nat Rev Cancer 10(11):794 (2010)
  In plants, as in animals, most cells that constitute the organism limit their reproductive potential in order to provide collective support for the immortal germ line. And, as in animals, the mechanisms that restrict the proliferation of somatic cells in plants can fail, leading to tumours. There are intriguing similarities in tumorigenesis between plants and animals, including the involvement of the retinoblastoma pathway as well as overlap with mechanisms that are used for stem cell maintenance. However, plant tumours are less frequent and are not as lethal as those in animals. We argue that fundamental differences between plant and animal development make it much more difficult for individual plant cells to escape communal controls.
• The genesis and evolution of high-grade serous ovarian cancer
  - Nat Rev Cancer 10(11):803 (2010)
  Germline mutation in either BRCA1 or BRCA2 is associated with an increased risk of ovarian cancer, particularly the most common invasive histotype — serous carcinoma. In addition, serous ovarian cancers have an unusually high frequency of other molecular events involving BRCA pathway dysfunction. Recent findings show a high frequency of TP53 mutation, chromosomal instability, distinct molecular subtypes and DNA copy number-driven changes in gene expression. These findings suggest a model in which homologous recombination repair deficiency initiates a cascade of molecular events that sculpt the evolution of high-grade serous ovarian cancer and dictate its response to therapy.