Latest Articles Include:
- From the editors
- Nat Rev Cancer 10(7):449 (2010)
The American Society of Clinical Oncology held its annual meeting at the start of June and reported several findings from a number of clinical trials investigating new targeted agents. Among these was a Phase III trial of an antibody, ipilimumab, which inhibits cytotoxic T lymphocyte antigen 4 (CTLA4).
- Tumorigenesis: Hormonally driven
- Nat Rev Cancer 10(7):451 (2010)
The ovarian hormones oestrogen and progesterone are inextricably linked to breast cancer. Not only do their levels influence disease risk and prognosis, but manipulating their activity also forms the basis for gold standard treatments.
- Metastasis: Pushing on through
- Nat Rev Cancer 10(7):452 (2010)
Metastasis is a complex process of which we still understand little, but the parallels between metastasis and cell invasion during development can give us some clues. During the development of a connection between uterine cells and vulval cells in the nematode Caenorhabditis elegans, one cell, the anchor cell (AC), has to invade through a basement membrane.
- Melanoma: Don't let sleeping cells lie
- Nat Rev Cancer 10(7):452 (2010)
Melanomas are heterogenous tumours that are highly metastastic, but patients with this disease can be cured if they are treated at an early stage before tumour cells colonize distant organs. Therefore, keeping the growth of primary tumours and metastases under control is one possible route to successful therapy.
- Therapy: An unhelpful hand
- Nat Rev Cancer 10(7):453 (2010)
Increased signalling through the insulin-like growth factor (IGF) pathway has been implicated in the progression of several types of human cancer. The IGF2 ligand is frequently overexpressed in colon and breast cancers, and inhibitors of one its receptors, IGF1 receptor (IGF1R), are in clinical trials.
- Transcription: We bonded — now make a decision
- Nat Rev Cancer 10(7):454 (2010)
p53 regulates the expression of genes involved in cell cycle arrest and apoptosis by binding to a DNA consensus sequence. Two recent papers by the groups of Thorsten Stiewe and Joaquín Espinosa provide insight into the mechanisms that influence the decision making between these two events.
- Mutation: It's the CpG content that counts
- Nat Rev Cancer 10(7):454 (2010)
The rate of neutral mutations — those that are not subject to natural selection — shows substantial variation, but the factors contributing to mutational rate have remained elusive. Now, new evidence indicates that the CpG content of DNA can influence the mutation rate of non-CpG-containing sequences, suggesting that the intrinsic properties of DNA sequences may be more important than the chromosomal environment in determining mutation rates and genome integrity.
- Oncogenes: Adding more to the Myc story
- Nat Rev Cancer 10(7):455 (2010)
The Myc family of transcription factors are well-known oncoproteins and three new studies contribute important insights into mechanisms of MYC regulation and the roles of MYCN in tumorigenesis and progression.Richard Young and colleagues demonstrate that MYC plays a key part in regulating transcriptional elongation by RNA polymerase II (Pol II).
- Covalent histone modifications — miswritten, misinterpreted and mis-erased in human cancers
- Nat Rev Cancer 10(7):457 (2010)
Post-translational modification of histones provides an important regulatory platform for processes such as gene transcription and DNA damage repair. It has become increasingly apparent that the misregulation of histone modification, which is caused by the deregulation of factors that mediate the modification installation, removal and/or interpretation, actively contributes to human cancer. In this Review, we summarize recent advances in understanding the interpretation of certain histone methylations by plant homeodomain finger-containing proteins, and how misreading, miswriting and mis-erasing of histone methylation marks can be associated with oncogenesis and progression. These observations provide us with a greater mechanistic understanding of epigenetic alterations in human cancers and might also help direct new therapeutic interventions in the future.
- Non-germline genetically engineered mouse models for translational cancer research
- Nat Rev Cancer 10(7):470 (2010)
Genetically engineered mouse models (GEMMs) of cancer have affected virtually all areas of cancer research. However, the accelerated discovery of new cancer genes emerging from large-scale cancer genomics and new chemical entities pouring from the drug discovery pipeline have strained the capacity of traditional germline mouse models to provide crucial insights. This Review introduces new approaches to modelling cancer, with emphasis on a growing collection of non-germline GEMMs (nGEMMs). These offer flexibility, speed and uniformity at reduced costs, thus paving the way for much needed throughput and practical preclinical therapeutic testing models.
- Cartilage tumours and bone development: molecular pathology and possible therapeutic targets
Bovée JV Hogendoorn PC Wunder JS Alman BA - Nat Rev Cancer 10(7):481 (2010)
As a group, cartilage tumours are the most common primary bone lesions. They range from benign lesions, such as enchondromas and osteochondromas, to malignant chondrosarcoma. The benign lesions result from the deregulation of the hedgehog signalling pathway, which is involved in normal bone development. These lesions can be the precursors of malignant chondrosarcomas, which are notoriously resistant to conventional chemotherapy and radiotherapy. Cytogenetic studies and mouse models are beginning to identify genes and signalling pathways that have roles in tumour progression, such as hedgehog, p53, insulin-like growth factor, cyclin-dependent kinase 4, hypoxia-inducible factor, matrix metalloproteinases, SRC and AKT, suggesting potential new therapeutic approaches.
- Sphingosine 1-phosphate and cancer
Pyne NJ Pyne S - Nat Rev Cancer 10(7):489 (2010)
There is substantial evidence that sphingosine 1-phosphate (S1P) is involved in cancer. S1P regulates processes such as inflammation, which can drive tumorigenesis; neovascularization, which provides cancer cells with nutrients and oxygen; and cell growth and survival. This occurs at multiple levels and involves S1P receptors, sphingosine kinases, S1P phosphatases and S1P lyase. This Review summarizes current research findings and examines the potential for new therapeutics designed to alter S1P signalling and function in cancer.
- Targeting the tumour vasculature: insights from physiological angiogenesis
- Nat Rev Cancer 10(7):505 (2010)
The cardiovascular system ensures the delivery of nutrients, oxygen, and blood and immune cells to all organs and tissues: it is also responsible for the removal of waste metabolites. The vascular system develops and matures through two tightly regulated processes: vasculogenesis and angiogenesis. Angiogenesis is active only under specific physiological conditions in healthy adults but the vasculature can be aberrantly activated to generate new blood vessels during pathological conditions such as cancer and chronic inflammation. In this Opinion article we discuss the parallels and differences in the angiogenic process under either a physiological or a pathological state, especially tumorigenesis.
- Envisioning the future of early anticancer drug development
Yap TA Sandhu SK Workman P de Bono JS - Nat Rev Cancer 10(7):514 (2010)
The development of novel molecularly targeted cancer therapeutics remains slow and expensive with many late-stage failures. There is an urgent need to accelerate this process by improving early clinical anticancer drug evaluation through modern and rational trial designs that incorporate predictive, pharmacokinetic, pharmacodynamic, pharmacogenomic and intermediate end-point biomarkers. In this article, we discuss current approaches and propose strategies that will potentially maximize benefit to patients and expedite the regulatory approvals of new anticancer drugs.
- Correspondence: The ABC of glycosylation
Perego P Gatti L Beretta GL - Nat Rev Cancer 10(7):523 (2010)
We read with great interest the Opinion article by Jamie Fletcher and colleagues, ABC transporters in cancer: more than just drug efflux pumps. Nature Rev. Cancer. 10, 147–156 (2010)
- Correspondence: Breast and prostate cancer: familial associations
- Nat Rev Cancer 10(7):523 (2010)
In a recent Opinion article by Gail Risbridger and colleagues, Breast and prostate cancer: more similar than different (Nature Rev. Cancer 10, 205–212 (2010)), the extensive biological similarities of the hormone-dependant pathways of breast and prostate cancers were discussed1.
- Corrigendum: Genetic variation in microRNA networks: the implications for cancer research
- Nat Rev Cancer 10(7):523 (2010)
There were several mistakes in TABLES 1–3 of this article. In TABLE 1 on page 385, for rs2910164 in hepatocelluar carcinoma the odds ratio data refer to males only. For rs11614913 in lung cancer the odds ratio is for both sexes and not for males only. For rs11614913 in oesophageal cancer the reference genotype should be CC/CT and the analysed genotype should be TT. For rs11614913 in breast cancer the reference genotype should be CC and the analysed genotypes should be CT and then TT. For rs895819 in breast cancer the reference genotype should be CT. In TABLE 2 on page 396, for the SEDT8 alleles, the miRNA binds the derived alleles and not the ancestral alleles. For the BCTRP allele, the miRNA binds deletion alleles that are derived and not insertion alleles that are ancestral. For the BMPR1B allele, the miRNA binds the C allele and not the derived allele. For the CD86 allele, the miRNA binds the ancestral allele and not the derived allele. In TABLE 3 on page 398, the! odds ratio given for GEMIN4 rs7813 is for all cases of renal cell carcinoma, not just clear cell carcinoma as indicated. For GEMIN3 rs197414 the cancer site should be bladder and not renal cell carcinoma and the reference is 35 and not 111. This has been corrected online.