Hot off the presses! Jan 01 Nat Rev Cancer

The Jan 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(1):1 (2011)
  
• Therapy: Multiple bypass problem for BRAF inhibition | PDF (114 KB)
  - Nat Rev Cancer 11(1):2 (2011)
  Inhibitors of BRAF are showing promise for the treatment of melanomas that express mutant BRAF-V600E, but the emergence of resistant disease is a growing concern. Two recent studies have identified novel resistance mechanisms and have suggested improved treatment strategies.
• Tumorigenesis: RB, lost in progression | PDF (253 KB)
  - Nat Rev Cancer 11(1):3 (2011)
  The retinoblastoma (RB) tumour suppressor is well known for its role in suppressing the transcription of genes required for S phase entry by repressing the activity of the E2F transcription factors. Inactivation of the RB pathway by mutations in different proteins upstream of RB is a common event in tumour development.
• Circulating tumour cells | PDF (97 KB)
  - Nat Rev Cancer 11(1):3 (2011)
  Three press releases from the 33rd Annual Cancer Therapy and Research Center–American Association of Cancer Research San Antonio Breast Cancer Symposium indicate that the presence of circulating tumour cells (CTCs) is prognostic for cancer recurrence and poor survival in women with early- and late-stage breast cancer.Results from SUCCESS, a randomized Phase III trial, which is assessing the effect of docetaxel and gemcitabine as adjuvant therapies in patients with early-stage breast cancer, indicate that women with one to four CTCs in their blood after surgery, but before receiving adjuvant chemotherapy, have an 88% increased risk of early disease recurrence and a 91% increased risk of death from this disease.
• Tumour suppressors: Selective justice | PDF (222 KB)
  - Nat Rev Cancer 11(1):4 (2011)
  The multi-talented 'guardian of the genome' p53 is fundamental for preventing tumour development. This was exemplified 3 years ago by three publications showing that the restoration of p53 function to p53-null tumours resulted in complete tumour regression in some animals.
• Stem cells: Tumour stem cells generate vasculature | PDF (207 KB)
  - Nat Rev Cancer 11(1):4 (2011)
  Glioblastoma is a highly angiogenic tumour and, although it is known that neural stem cells closely interact with the vascular niche, the origins of the endothelial cells in this malignancy are poorly understood. Two new papers show that stem-like cells in the tumour can differentiate into endothelial cells, thereby generating the tumour vasculature.
• Epigenetics | Therapy | Tumorigenesis | PDF (130 KB)
  - Nat Rev Cancer 11(1):5 (2011)
  Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway Jagani, Z.et al. Nature Med. 16, 1429–1433 (2010)
• MicroRNA: Micro-loops in NF-κB signalling | PDF (292 KB)
  - Nat Rev Cancer 11(1):6 (2011)
  Nuclear factor-κB (NF-κB) signalling is constitutively activated in pancreatic adenocarcinoma, but genetic activation of members of the NF-κB pathway does not appear to be the cause. So, Yong Li and colleagues investigated what might activate this pathway in pancreatic adenocarcinoma.
• Stem cells: Self-sufficient | PDF (298 KB)
  - Nat Rev Cancer 11(1):6 (2011)
  The highly organized small intestinal crypt has proved to be an ideal tissue in which to study stem cells — we knew where they were in the crypt long before we knew precisely which cells they were. Now, Toshiro Sato, Hans Clevers and colleagues have identified the cells that maintain these stem cells in a self-renewing state: the Paneth cells.
• DNA repair: A single-edged sword? | PDF (130 KB)
  - Nat Rev Cancer 11(1):7 (2011)
  Deficiencies in DNA repair processes modulate both tumorigenesis and chemotherapy response. Therapeutic inhibition of DNA repair can sensitize cancer cells to chemotherapy or can function as a synthetic lethal strategy for the treatment of cancers with certain DNA repair defects.
• Therapeutics: RNA device rewires cellular networks | PDF (246 KB)
  - Nat Rev Cancer 11(1):8 (2011)
  Synthetic devices that translate molecular inputs into gene expression changes are valuable for manipulating cellular behaviour, but until now these circuits have only been able to respond to a limited set of inputs, such as transcription factors. However, a new synthetic device based on RNA can respond sensitively to alterations in the levels of endogenous signalling molecules, and so can potentially link disease-associated pathways to cell fate decisions.
• Old dog, new tricks | PDF (94 KB)
  - Nat Rev Cancer 11(1):8 (2011)
  A junior aspirin (75 mg) a day might keep cancer at bay was the headline-grabbing cancer story this month. In a report published in The Lancet, Peter Rothwell and colleagues from the University of Oxford, UK, found that patients who regularly take the humble aspirin for other ailments for 5 years or more have a reduced incidence of prostate, stomach, colorectal, oesophageal and lung cancer.
• The molecular biology of head and neck cancer
  - Nat Rev Cancer 11(1):9 (2011)
  Head and neck squamous cell carcinomas (HNSCCs) are caused by tobacco and alcohol consumption and by infection with high-risk types of human papillomavirus (HPV). Tumours often develop within preneoplastic fields of genetically altered cells. The persistence of these fields after treatment presents a major challenge, because it might lead to local recurrences and second primary tumours that are responsible for a large proportion of deaths. Aberrant signalling pathways have been identified in HNSCCs and inhibition of epidermal growth factor receptor (EGFR) has proved a successful therapeutic strategy. In this Review, we discuss the recent literature on tumour heterogeneity, field cancerization, molecular pathogenesis and the underlying causative cancer genes that can be exploited for novel and personalized treatments of patients with HNSCC.
• For better or for worse: the role of Pim oncogenes in tumorigenesis
  - Nat Rev Cancer 11(1):23 (2011)
  Pim oncogenes are overexpressed in a wide range of tumours from a haematological and epithelial origin. Pim genes encode serine/threonine kinases that have been shown to counteract the increased sensitivity to apoptosis induction that is associated with MYC-driven tumorigenesis. Recently, considerable progress has been made in characterizing the pathways of PIM-mediated survival signalling. Given the unique structure of their active site and the minimal phenotype of mice mutant for all Pim family members, these oncogenes might be promising targets for highly specific and selective drugs with favourable toxicity profiles. In this Review, we discuss the physiological functions and oncogenic activities of Pim kinases.
• Inside the human cancer tyrosine phosphatome
  - Nat Rev Cancer 11(1):35 (2011)
  Members of the protein tyrosine phosphatase (Ptp) family dephosphorylate target proteins and counter the activities of protein tyrosine kinases that are involved in cellular phosphorylation and signalling. As such, certain PTPs might be tumour suppressors. Indeed, PTPs play an important part in the inhibition or control of growth, but accumulating evidence indicates that some PTPs may exert oncogenic functions. Recent large-scale genetic analyses of various human tumours have highlighted the relevance of PTPs either as putative tumour suppressors or as candidate oncoproteins. Progress in understanding the regulation and function of PTPs has provided insights into which PTPs might be potential therapeutic targets in human cancer.
• Cell lineage and cell death: Caenorhabditis elegans and cancer research
  - Nat Rev Cancer 11(1):50 (2011)
  Cancer is a complex disease in which cells have circumvented normal restraints on tissue growth and have acquired complex abnormalities in their genomes, posing a considerable challenge to identifying the pathways and mechanisms that drive fundamental aspects of the malignant phenotype. Genetic analyses of the normal development of the nematode Caenorhabditis elegans have revealed evolutionarily conserved mechanisms through which individual cells establish their fates, and how they make and execute the decision to survive or undergo programmed cell death. The pathways identified through these studies have mammalian counterparts that are co-opted by malignant cells. Effective cancer drugs now target some of these pathways, and more are likely to be discovered.
• RNA interference in the clinic: challenges and future directions
  - Nat Rev Cancer 11(1):59 (2011)
  Inherent difficulties with blocking many desirable targets using conventional approaches have prompted many to consider using RNA interference (RNAi) as a therapeutic approach. Although exploitation of RNAi has immense potential as a cancer therapeutic, many physiological obstacles stand in the way of successful and efficient delivery. This Review explores current challenges to the development of synthetic RNAi-based therapies and considers new approaches to circumvent biological barriers, to avoid intolerable side effects and to achieve controlled and sustained release.
• What is the malignant nature of human ductal carcinoma in situ?
  - Nat Rev Cancer 11(1):68 (2011)
  Invasive, genetically abnormal carcinoma progenitor cells have been propagated from human and mouse breast ductal carcinoma in situ (DCIS) lesions, providing new insights into breast cancer progression. The survival of DCIS cells in the hypoxic, nutrient-deprived intraductal niche could promote genetic instability and the derepression of the invasive phenotype. Understanding potential survival mechanisms, such as autophagy, that might be functioning in DCIS lesions provides strategies for arresting invasion at the pre-malignant stage. A new, open trial of neoadjuvant therapy for patients with DCIS constitutes a model for testing investigational agents that target malignant progenitor cells in the intraductal niche.
• Correspondence: Cancer is an ancient disease: the case for better palaeoepidemiological and molecular studies
  - Nat Rev Cancer 11(1):76 (2011)
  I read with great interest the recent Science and Society article (Cancer: an old disease, a new disease or something in between? Nature Rev. Cancer10, 728–733 (2010)