Hot off the presses! Aug 01 Nat Rev Cancer

The Aug 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:

• From the editors
  - Nat Rev Cancer 9(8):527 (2009)
  
• Chromosomal instability: It's about the geometry
  - Nat Rev Cancer 9(8):529 (2009)
  
• Metastasis: WAVEing goodbye to invasion
  - Nat Rev Cancer 9(8):530 (2009)
  
• Endocytosis: Increased trafficking
  - Nat Rev Cancer 9(8):530 (2009)
  
• Making waves
  - Nat Rev Cancer 9(8):530 (2009)
  
• Metastasis: T-ALL order
  - Nat Rev Cancer 9(8):531 (2009)
  
• In brief: Signalling, Metastasis, Metabolism, Signalling
  - Nat Rev Cancer 9(8):532 (2009)
  
• Therapy: microRNA suppresses liver cancer
  - Nat Rev Cancer 9(8):532 (2009)
  
• Non-coding RNA: Dicing with lung cancer
  - Nat Rev Cancer 9(8):532 (2009)
  
• Synthetic lethal success, Anti-VEGF alternative
  - Nat Rev Cancer 9(8):533 (2009)
  
• Therapy: Special delivery
  - Nat Rev Cancer 9(8):534 (2009)
  
• Tumorigenesis: Cone cells set the stage
  - Nat Rev Cancer 9(8):534 (2009)
  
• Cancer pain: Getting on my nerves
  - Nat Rev Cancer 9(8):535 (2009)
  
• Signal integration by JNK and p38 MAPK pathways in cancer development
  - Nat Rev Cancer 9(8):537-549 (2009)
  Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) family members function in a cell context-specific and cell type-specific manner to integrate signals that affect proliferation, differentiation, survival and migration. Consistent with the importance of these events in tumorigenesis, JNK and p38 MAPK signalling is associated with cancers in humans and mice. Studies in mouse models have been essential to better understand how these MAPKs control cancer development, and these models are expected to provide new strategies for the design of improved therapeutic approaches. In this Review we highlight the recent progress made in defining the functions of the JNK and p38 MAPK pathways in different cancers.
• Targeting PI3K signalling in cancer: opportunities, challenges and limitations
  - Nat Rev Cancer 9(8):550-562 (2009)
  There are ample genetic and laboratory studies that suggest the PI3K–Akt pathway is vital to the growth and survival of cancer cells. Inhibitors targeting this pathway are entering the clinic at a rapid pace. In this Review, the therapeutic potential of drugs targeting PI3K–Akt signalling for the treatment of cancer is discussed. I focus on the advantages and drawbacks of different treatment strategies for targeting this pathway, the cancers that might respond best to these therapies and the challenges and limitations that confront their clinical development.
• The LKB1–AMPK pathway: metabolism and growth control in tumour suppression
  - Nat Rev Cancer 9(8):563-575 (2009)
  In the past decade, studies of the human tumour suppressor LKB1 have uncovered a novel signalling pathway that links cell metabolism to growth control and cell polarity. LKB1 encodes a serine–threonine kinase that directly phosphorylates and activates AMPK, a central metabolic sensor. AMPK regulates lipid, cholesterol and glucose metabolism in specialized metabolic tissues, such as liver, muscle and adipose tissue. This function has made AMPK a key therapeutic target in patients with diabetes. The connection of AMPK with several tumour suppressors suggests that therapeutic manipulation of this pathway using established diabetes drugs warrants further investigation in patients with cancer.
• CYP2D6 and tamoxifen: DNA matters in breast cancer
  - Nat Rev Cancer 9(8):576-586 (2009)
  Tamoxifen is the most widely used anti-oestrogen for the treatment of hormone-dependent breast cancer. The pharmacological activity of tamoxifen is dependent on its conversion by the hepatic drug-metabolizing enzyme cytochrome P450 2D6 (CYP2D6) to its abundant metabolite, endoxifen. Patients with reduced CYP2D6 activity, as a result of either their genotype or induction by the co-administration of drugs that inhibit CYP2D6 function, produce little endoxifen and seem to derive inferior therapeutic benefit from tamoxifen. Here we review the existing data that relate CYP2D6 genotypes to response to tamoxifen and discuss whether the analysis of the CYP2D6 genotype might be an early example of a pharmacogenetic tool for optimizing breast cancer therapy.
• Crosstalk of Notch with p53 and p63 in cancer growth control
  - Nat Rev Cancer 9(8):587-595 (2009)
  Understanding the complexity of cancer depends on an elucidation of the underlying regulatory networks, at the cellular and intercellular levels and in their temporal dimension. This Opinion article focuses on the multilevel crosstalk between the Notch pathway and the p53 and p63 pathways. These two coordinated signalling modules are at the interface of external damaging signals and control of stem cell potential and differentiation. Positive or negative reciprocal regulation of the two pathways can vary with cell type and cancer stage. Therefore, selective or combined targeting of the two pathways could improve the efficacy and reduce the toxicity of cancer therapies.
• Assessing cancer risks of low-dose radiation
  - Nat Rev Cancer 9(8):596-604 (2009)
  Ionizing radiation is considered a non-threshold carcinogen. However, quantifying the risk of the more commonly encountered low and/or protracted radiation exposures remains problematic and subject to uncertainty. Therefore, a major challenge lies in providing a sound mechanistic understanding of low-dose radiation carcinogenesis. This Perspective article considers whether differences exist between the effects mediated by high- and low-dose radiation exposure and how this affects the assessment of low-dose cancer risk.
• Corrigendum: High throughput insertional mutagenesis screens in mice to identify oncogenic networks
  - Nat Rev Cancer 9(8):604 (2009)
  On page 398 of this article, the highlighted description for reference 12 should instead be attributed to reference 11: An elegant study in which a hypomorphic Blm allele is used to induce LOH of retrovirally inactivated tumour suppressor genes. On page 399, the highlighted description for reference 54 should instead be attributed to reference 56: These authors demonstrate that insertional mutagenesis can be used to screen for genes that confer resistance to therapeutic agents in vivo.
• Corrigendum: Wildlife cancer: a conservation perspective
  - Nat Rev Cancer 9(8):605 (2009)
  In table 1 on page 521 of the above article, the associated virus for flatback turtle (Natator depressus), olive ridley turtle (Lepidochelys olivacea), loggerhead turtle (Caretta caretta), leatherback turtle (Dermochelys coriacea), Kemp's ridley turtle (L. kempii) and hawksbill turtle (Eretmochelys imbricata) was mistakenly indicated as papillomavirus. These entries have therefore been removed from the table. Reference 154 has also been removed from the article because other references in the main text discuss the virus association in specific turtle species. Accordingly, references 155–162 have been renumbered as references 154–161.