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 11(11):755 (2011)
  
• Metabolism: Letting glucose take hold | PDF (169 KB)
  - Nat Rev Cancer 11(11):756 (2011)
  Cancer cells often reprogram metabolic pathways in favour of glucose metabolism, glycolysis and anapleurotic pathways that promote growth and survival. Interestingly, many genes that are associated with type 2 diabetes — which is a disorder of glucose metabolism — are proto-oncogenes and regulators of proliferation.
• Tumorigenesis: USP1 keeps ID proteins stable | PDF (309 KB)
  - Nat Rev Cancer 11(11):757 (2011)
  Basic helix–loop–helix transcription factors, which are regulators of development and differentiation, can be suppressed by inhibitor of DNA binding (ID) proteins. ID proteins are abundant in embryonic and adult stem cells, and they are overexpressed in some dedifferentiated tumours.
• Metabolism: Catabolic effects | PDF (199 KB)
  - Nat Rev Cancer 11(11):757 (2011)
  The enzymes indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO) mediate the breakdown of Trp to kynurenine (Kyn). IDO proteins inhibit antitumour immune responses and IDO inhibitors are being tested in patients with cancer, but the mechanisms by which Trp catabolism promotes tumorigenesis, and the contributions of TDO, are unknown.
• Tumour suppressors: HOTS makes antisense | PDF (698 KB)
  - Nat Rev Cancer 11(11):758 (2011)
  The H19–insulin-like growth factor 2 (IGF2) locus is closely associated with the development of a number of embryonal tumours, including Wilm's tumours. Patrick Onyango and Andrew Feinberg have found that an antisense transcript encoded by H19 is a probable tumour suppressor.
• Pancreatic cancer: Fibroblast co-conspirators | PDF (233 KB)
  - Nat Rev Cancer 11(11):758 (2011)
  The importance of the tumour microenvironment for cancer progression is now well established, but can tumour–stromal interactions be targeted for therapeutic benefit? Using a mouse model of pancreatic ductal adenocarcinoma (PDAC), Hideaki Ijichi and colleagues have provided preclinical data showing that targeting chemokine signalling in stromal fibroblasts can improve survival.
• Gene expression: Variety is the splice of strife | PDF (339 KB)
  - Nat Rev Cancer 11(11):759 (2011)
  Alternative splicing is a key mechanism for enhancing the variety of RNAs (and therefore proteins) that are encoded by genes. Two new reports add weight to our growing appreciation of splicing disruptions in diseases such as cancer.
• Tumour suppressors: Silencing heterochromatin | PDF (169 KB)
  - Nat Rev Cancer 11(11):760 (2011)
  Germline mutation of BRCA1 generates a significant lifetime risk of developing breast and ovarian cancer. Why this mutation is almost certain to produce such tumours is not clear, despite our knowledge of the involvement of BRCA1 in DNA repair and genomic stability.
• Aneuploidy: Lack of a full set is damaging | PDF (110 KB)
  - Nat Rev Cancer 11(11):760 (2011)
  Whole chromosomal instability (CIN) is known to contribute to aneuploidy, but can it also cause DNA damage? In cells in which aneuploidy is promoted by a drug that induces incorrect kinetochore attachment, and hence lagging chromosomes at mitosis, sites of DNA damage and chromosomal rearrangements are increased.
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  - Nat Rev Cancer 11(11):760 (2011)
  
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  - Nat Rev Cancer 11(11):760 (2011)
  
• RAS oncogenes: weaving a tumorigenic web
  - Nat Rev Cancer 11(11):761 (2011)
  RAS proteins are essential components of signalling pathways that emanate from cell surface receptors. Oncogenic activation of these proteins owing to missense mutations is frequently detected in several types of cancer. A wealth of biochemical and genetic studies indicates that RAS proteins control a complex molecular circuitry that consists of a wide array of interconnecting pathways. In this Review, we describe how RAS oncogenes exploit their extensive signalling reach to affect multiple cellular processes that drive tumorigenesis.
• Targeting protein prenylation for cancer therapy
  - Nat Rev Cancer 11(11):775 (2011)
  Protein farnesylation and geranylgeranylation, together referred to as prenylation, are lipid post-translational modifications that are required for the transforming activity of many oncogenic proteins, including some RAS family members. This observation prompted the development of inhibitors of farnesyltransferase (FT) and geranylgeranyltransferase 1 (GGT1) as potential anticancer drugs. In this Review, we discuss the mechanisms by which FT and GGT1 inhibitors (FTIs and GGTIs, respectively) affect signal transduction pathways, cell cycle progression, proliferation and cell survival. In contrast to their preclinical efficacy, only a small subset of patients responds to FTIs. Identifying tumours that depend on farnesylation for survival remains a challenge, and strategies to overcome this are discussed. One GGTI has recently entered the clinic, and the safety and efficacy of GGTIs await results from clinical trials.
• TRIM proteins and cancer
  - Nat Rev Cancer 11(11):792 (2011)
  Emerging clinical evidence shows that the deregulation of ubiquitin-mediated degradation of oncogene products or tumour suppressors is likely to be involved in the aetiology of carcinomas and leukaemias. Recent studies have indicated that some members of the tripartite motif (TRIM) proteins (one of the subfamilies of the RING type E3 ubiquitin ligases) function as important regulators for carcinogenesis. This Review focuses on TRIM proteins that are involved in tumour development and progression.
• Novel cancer immunotherapy agents with survival benefit: recent successes and next steps
  - Nat Rev Cancer 11(11):805 (2011)
  The US Food and Drug Administration (FDA) recently approved two novel immunotherapy agents, sipuleucel-T and ipilimumab, which showed a survival benefit for patients with metastatic prostate cancer and melanoma, respectively. The mechanisms by which these agents provideclinical benefit are not completely understood. However, knowledge of these mechanisms will be crucial for probing human immune responses and tumour biology in order to understand what distinguishes responders from non-responders. The following next steps are necessary: first, the development of immune-monitoring strategies for the identification of relevant biomarkers; second, the establishment of guidelines for the assessment of clinical end points; and third, the evaluation of combination therapy strategies to improve clinical benefit.
• Parkinson's disease and cancer: two wars, one front
  - Nat Rev Cancer 11(11):812 (2011)
  Parkinson's disease is caused by the premature death of neurons in the midbrain. By contrast, cancer spawns from cells that refuse to die. We would therefore expect their pathogenic mechanisms to be very different. However, recent genetic studies and emerging functional work show that strikingly similar and overlapping pathways are involved in both diseases. We consider these areas of convergence and discuss how insights from one disease can inform us about, and possibly help us to treat, the other.
• Aminoacyl-tRNA synthetases and tumorigenesis: more than housekeeping
  - Nat Rev Cancer 11(11):813 (2011)
  Nature Reviews Cancer11, 708–718 (2011) In Figure 4c of this article, data for AIMP1-3 were all mistakenly labelled as AIMP3. This has now been corrected online.
• Correspondence: ESR1 gene amplification: another mechanism regulating the cellular levels of ERα
  - Nat Rev Cancer 11(11):823 (2011)
  We read with great interest the Review (The different roles of ER subtypes in cancer biology and therapy. Nature Rev. Cancer, 597–608 (2011)