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:

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  - Nat Rev Cancer 10(12):809 (2010)
  
• Tumour Suppression: YAP tips the balance | PDF (154 KB)
  - Nat Rev Cancer 10(12):811 (2010)
  Yes-associated protein (YAP) is a transcriptional co-activator that shuttles between the cytoplasm and the nucleus. The role of YAP-mediated gene expression in tumorigenesis is unclear, as there are reports that YAP has both oncogenic and tumour suppressive roles.
• Signalling: Finding your inner activator | PDF (216 KB)
  - Nat Rev Cancer 10(12):812 (2010)
  A recent paper published in Cell extends the current understanding of how ligand-mediated activation ofepidermal growth factor receptors (EGFRs) is regulated by showing that a cytoplasmic family of proteins known as the cytohesins affect the conformation of EGFRs.Cytohesins are guanine–nucleotide exchange factors (GEFs) for the ADP ribosylation factors (ARFs) that are involved in vesicular trafficking and cytoskeletal changes.
• Transcription factors: MYC matters | PDF (293 KB)
  - Nat Rev Cancer 10(12):812 (2010)
  Mutation or aberrant regulation of the transcription factor MYC is a common feature of many cancers. Two new studies have added more details to the complexity of MYC regulation in cell development and growth pathways, underscoring the importance of MYC in tumorigenesis.
• Mutagenesis | Signalling | Oncogenes | Therapeutics | PDF (158 KB)
  - Nat Rev Cancer 10(12):813 (2010)
  PiggyBac transposon mutatgenesis: a tool for cancer gene discovery in mice Rad, R.et al. Science, 14 Oct 2010 (doi: 10.1126/science.1193004)
• Therapy: Expanding the horizons of PARP inhibitors | PDF (192 KB)
  - Nat Rev Cancer 10(12):814 (2010)
  Aberrant vascularity in tumours results in hypoxic tumour regions that are distant from blood vessels, as oxygen is poorly delivered to these areas. As drugs are also not efficiently delivered in these circumstances, intratumoral hypoxia is associated with treatment resistance.
• Lung cancer: A regulator of senescence | PDF (225 KB)
  - Nat Rev Cancer 10(12):814 (2010)
  KRAS mutations are common in cancers, but oncogenic KRAS has differing effects — in some cases, it induces hyperproliferation, whereas in others it leads to senescence. A recent study has identified the transcription factor Wilms tumour 1 (WT1) as a key regulator of these two alternative outcomes, providing new insights that might have therapeutic implications for KRAS-driven lung cancers.
• Tumour suppression: The burning issue of p63 | PDF (187 KB)
  - Nat Rev Cancer 10(12):814 (2010)
  The involvement of the p53 family member p63 in tumour suppression and in promoting tumorigenesis has been a matter of debate, and a new paper in Nature now clarifies the tumour suppressor function of p63.The full-length isoform of p63 that contains the transactivation (TA) domain, TAp63, is thought to be a tumour suppressor; so Su, Chakravarti and colleagues investigated this further with cohorts of knockout mice.
• Development | Therapy | Small RNAs | Therapy | PDF (174 KB)
  - Nat Rev Cancer 10(12):815 (2010)
  Drosophila SPARC is a self-protective signal expressed by loser cells during cell competition Portela, M.et al. Dev. Cell 19, 562–573 (2010)
• Lymphomagenesis: The ARTS of cell death | PDF (158 KB)
  - Nat Rev Cancer 10(12):816 (2010)
  The importance of apoptosis as a tumour suppressive mechanism is well documented, especially in the haematopoietic system, but which components of the apoptotic pathway, through either their gain or their loss of function, can promote tumour development is still being established. A recent paper in Genes and Development indicates that reduced expression of the pro-apoptotic protein ARTS, which is an inhibitor of X-linked inhibitor of apoptosis (XIAP), can promote the development of leukaemia and lymphoma by enabling the aberrant survival of haematopoietic stem and progenitor cells.
• Signalling: Without the sun | PDF (179 KB)
  - Nat Rev Cancer 10(12):816 (2010)
  The second messenger cyclic AMP (cAMP) has a key role in numerous cellular processes. In response to melanocyte-stimulating hormone (MSH) cAMP enhances skin pigmentation and protects against ultraviolet (UV)-induced damage, features that imply it would be an attractive skin cancer prevention agent.
• ALK and resistance | PDF (165 KB)
  - Nat Rev Cancer 10(12):817 (2010)
  A small proportion of non-small-cell lung cancers (between 2% and 7%) have a chromosomal translocation that results in the fusion of echinoderm microtubule-associated protein-like kinase 4 (EML4) with anaplastic lymphoma kinase (ALK). Results from a two-part, Phase I trial of one ALK inhibitor, crizotinib (Pfizer), have recently been reported in the New England Journal of Medicine.
• SIRT1: recent lessons from mouse models
  - Nat Rev Cancer 10(12):819 (2010)
  The family of protein deacetylases represented by yeast Sir2 has been the focus of intense investigation because of the longevity activity of Sir2 in yeast, worms and flies. Research in mammals has mainly focused on SIRT1, the closest homologue of Sir2. Emerging evidence from mouse models is yielding a sharper picture, in which SIRT1 is a potent protector from ageing-associated pathologies, such as diabetes, liver steatosis, cardiovascular disease, neurodegeneration and, importantly, various types of cancer.
• Shared and separate functions of polo-like kinases and aurora kinases in cancer
  - Nat Rev Cancer 10(12):825 (2010)
  Large numbers of inhibitors for polo-like kinases and aurora kinases are currently being evaluated as anticancer drugs. Interest in these drugs is fuelled by the idea that these kinases have unique functions in mitosis. Within the polo-like kinase family, the emphasis for targeted therapies has been on polo-like kinase 1 (PLK1), and in the aurora kinase family drugs have been developed to specifically target aurora kinase A (AURKA; also known as STK6) and/or aurora kinase B (AURKB; also known as STK12). Information on the selectivity of these compounds in vivo is limited, but it is likely that off-target effects within the same kinase families will affect efficacy and toxicity profiles. In addition, it is becoming clear that interplay between polo-like kinases and aurora kinases is much more extensive than initially anticipated, and that both kinase families are important factors in the response to classical chemotherapeutics that damage the genome or the mitotic spind! le. In this Review we discuss the implications of these novel insights on the clinical applicability of polo-like kinase and aurora kinase inhibitors.
• Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy?
  - Nat Rev Cancer 10(12):842 (2010)
  There is now considerable and increasing evidence for a causal role for aberrant activity of the Ras superfamily of small GTPases in human cancers. These GTPases function as GDP–GTP-regulated binary switches that control many fundamental cellular processes. A common mechanism of GTPase deregulation in cancer is the deregulated expression and/or activity of their regulatory proteins, guanine nucleotide exchange factors (GEFs) that promote formation of the active GTP-bound state and GTPase-activating proteins (GAPs) that return the GTPase to its GDP-bound inactive state. In this Review, we assess the association of GEFs and GAPs with cancer and their druggability for cancer therapeutics.
• Integrin signalling adaptors: not only figurants in the cancer story
  - Nat Rev Cancer 10(12):858 (2010)
  Current evidence highlights the ability of adaptor (or scaffold) proteins to create signalling platforms that drive cellular transformation upon integrin-dependent adhesion and growth factor receptor activation. The understanding of the biological effects that are regulated by these adaptors in tumours might be crucial for the identification of new targets and the development of innovative therapeutic strategies for human cancer. In this Review we discuss the relevance of adaptor proteins in signalling that originates from integrin-mediated cell–extracellular matrix (ECM) adhesion and growth factor stimulation in the context of cell transformation and tumour progression. We specifically underline the contribution of p130 Crk-associated substrate (p130CAS; also known as BCAR1), neural precursor cell expressed, developmentally down-regulated 9 (NEDD9; also known as HEF1), CRK and the integrin-linked kinase (ILK)–pinch–parvin (IPP) complex to cancer, along with the ! more recently identified p140 Cas-associated protein (p140CAP; also known as SRCIN1).
• Does tumour dormancy offer a therapeutic target?
  - Nat Rev Cancer 10(12):871 (2010)
  The increasing number of cancer survivors is cause for celebration, but this expanding population has highlighted the problem of tumour dormancy, which can lead to relapse. As we start to understand more about the biology of dormant cancer cells, we can begin to address how best to treat this form of disease. Preclinical models and initial clinical trials, as exemplified in patients with breast cancer, are paving the way to address how best to treat long-term cancer survivors to minimize the risk of cancer recurrence.
• Why do viruses cause cancer? Highlights of the first century of human tumour virology
  - Nat Rev Cancer 10(12):878 (2010)
  The year 2011 marks the centenary of Francis Peyton Rous's landmark experiments on an avian cancer virus. Since then, seven human viruses have been found to cause 10–15% of human cancers worldwide. Viruses have been central to modern cancer research and provide profound insights into both infectious and non-infectious cancer causes. This diverse group of viruses reveals unexpected connections between innate immunity, immune sensors and tumour suppressor signalling that control both viral infection and cancer. This Timeline article describes common features of human tumour viruses and discusses how new technologies can be used to identify infectious causes of cancer.
• Integrins in cancer: biological implications and therapeutic opportunities
  - Nat Rev Cancer 10(12):890 (2010)
  On page 17 of this article, in the section Targeting αvβ3 and αvβ5 the sentence at the start of the second paragraph that reads "Cilengitide is an inhibitor of both αvβ3 and αvβ5 integrins, and it was selected in our laboratory by screening a library of cyclic RGD peptides in a cell-free receptor assay for their capacity to inhibit integrins αvβ3 and αvβ5 but not αΙΙbβ3 REF. 130)." was incorrectly phrased. The corrected sentence with additional references is given below. "Cilengitide is an inhibitor of both αvβ3 and αvβ5 integrins. We had shown that αvβ3 and αvβ5 integrins were important regulators of angiogenesis and tumour growth49,51,191, 192 and developed a cell-free receptor assay to select for antagonists of integrins αvβ3 and αvβ5 that did not effect integrin αΙΙbβ3 REF. 130). This assay was used to screen a library of integrin binding cyclic RGD peptides designed and synthesized by H. Kessler and colleagues for αvβ3 activity and selectivity193, 194, 195 from which cilengitide was developed196".
• IAPs: from caspase inhibitors to modulators of NF-κB, inflammation and cancer
  - Nat Rev Cancer 10(12):890 (2010)
  On page 574 of this article, the following text was missing from the Acknowledgements. M.G.-H. is supported by grants from the Villum Kann Rasmussen Foundation (VKR07-074), Denmark, and Danish Cancer Society (DP08052 and R2-A206-09-S2). The authors acknowledge National Health Service funding to the National Institute for Health Research Biomedical Research Centre at the Royal Marsden Hospital, UK.