Latest Articles Include:
- From the editors
- Nature Reviews Cancer 10(4):231 (2010)
April 2010 Vol 10 No 4 * Research Highlights * Reviews * Perspectives Also this month: * Article series: Models of cancer MYC * Previous About the cover From the editors p231 | doi:10.1038/nrc2839 Comment: What are the hallmarks of cancer? p232 | doi:10.1038/nrc2827 Research Highlights Genetics: Mito messages | PDF (146 KB) p235 | doi:10.1038/nrc2834 A new method allows the identification of rare mutations in mitochondrial DNA that differ between normal and cancer cells. Signalling: Fly strike! | PDF (311 KB) p236 | doi:10.1038/nrc2829 Another member of the hippo–salvador–warts pathway has been identified. Treatment: Lighting the way | PDF (171 KB) p236 | doi:10.1038/nrc2833 Fluorescent probes that specifically label tumours improve the surgical removal of tumours. Signalling: RAF complexities spark caution | PDF (238 KB) p237 | doi:10.1038/nrc2837 Recent results indicate that stringent profiling of tumours will be needed prior to the use of RAF inhibitors. Cancer epigenetics: Long-range silencing | PDF (280 KB) p238 | doi:10.1038/nrc2828 Long-range epigenetic silencing decreases transcriptional plasticity in prostate cancer. Tumour suppressors: A new role for Dok | PDF (223 KB) p238 | doi:10.1038/nrc2835 DOK2 is frequently deleted in human lung cancer and suppresses lung cancer cell growth. In brief Metastasis | Leukaemogenesis | PDF (177 KB) p238 | doi:10.1038/nrc2838 Glioblastoma: Recurrence blocked | PDF (234 KB) p239 | doi:10.1038/nrc2836 Glioblastoma radiotherapy might be improved by inhibitors of vasculogenesis rather than angiogenesis. Reviews Article series: Models of cancer Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents Sreenath V. Sharma, Daniel A. Haber & Jeff Settleman p241 | doi:10.1038/nrc2820 Tumour-derived cell lines are an important model for the discovery and development of new anticancer drugs. The recent development of large panels of cell lines and high-throughput technologies has revitalized this field, and this Review discusses how these tools can be used to screen anticancer agents. * Abstract * Full Text * PDF (508 KB) Translational control in cancer Deborah Silvera, Silvia C. Formenti & Robert J. Schneider p254 | doi:10.1038/nrc2824 Effects on both global protein synthesis and selective translation of specific mRNAs can contribute to cancer development and progression. How are components of the translation machinery altered in cancer, and can these be targeted therapeutically? * Abstract * Full Text * PDF (530 KB) Targeting metabolic transformation for cancer therapy Daniel A. Tennant, Raúl V. Durán & Eyal Gottlieb p267 | doi:10.1038/nrc2817 This Review discusses the progress made with developing drugs that specifically target the altered metabolic pathways of tumours and suggests additional targets that might also be beneficial. * Abstract * Full Text * PDF (426 KB) The regulatory crosstalk between kinases and proteases in cancer Carlos López-Otín & Tony Hunter p278 | doi:10.1038/nrc2823 Many proteases are regulated by phosphorylation, and many kinases are regulated by proteolytic cleavage. This Review examines kinase–protease interactions and their functional effects in cancer in depth, revealing the enormous diversity and complexity of this crosstalk. * Abstract * Full Text * PDF (783 KB) * Supplementary information Perspectives Opinion PARP inhibition: PARP1 and beyond Michèle Rouleau, Anand Patel, Michael J. Hendzel, Scott H. Kaufmann & Guy G. Poirier p293 | doi:10.1038/nrc2812 Recent findings have thrust poly(ADP-ribose) polymerases (PARPs) into the limelight as potential chemotherapeutic targets. What is known about the structures and functions of the family of PARP enzymes and which questions do we need answered to guide the rational development of PARP inhibitors as anticancer agents? * Abstract * Full Text * PDF (415 KB) Article series: MYC Opinion MYC as a regulator of ribosome biogenesis and protein synthesis Jan van Riggelen, Alper Yetil & Dean W. Felsher p301 | doi:10.1038/nrc2819 Recently, MYC has been shown to serve as a direct regulator of ribosome biogenesis and therefore coordinates protein synthesis. Could the regulation of ribosome biogenesis by MYC be necessary for its role in tumorigenesis? * Abstract * Full Text * PDF (436 KB) Erratum: Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer Robert R. Jenq & Marcel R. M. Van den Brink p309 | doi:10.1038/nrc2825 * Full Text * PDF (86 KB) Corrigendum: Microtubules and resistance to tubulin-binding agents Maria Kavallaris p309 | doi:10.1038/nrc2830 * Full Text * PDF (86 KB) - Comment: What are the hallmarks of cancer?
- Nature Reviews Cancer 10(4):232 (2010)
Cancer is a complex disease that develops as a result of genetic and epigenetic changes in tumour cells and the surrounding microenvironment. Systemic changes are also likely to contribute to the progression of this disease. - Genetics: Mito messages
- Nature Reviews Cancer 10(4):235 (2010)
A major goal of cancer research is to understand how to counteract mechanisms that underlie the ability of cancers to kill the patient or, in other words, to be malignant. To this end, the puzzling complexity of numerous and interrelated properties of cancers was distilled 10 years ago into "six essential alterations in cell physiology that collectively dictate malignant growth: self-sufficiency in growth signals, insensitivity to growth-inhibitory (antigrowth) signals, evasion of programmed cell death (apoptosis), limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis" (Douglas Hanahan and Robert Weinberg)1. - Signalling: Fly strike!
- Nature Reviews Cancer 10(4):236 (2010)
With the resurgence of interest in cancer cell metabolomics, greater attention has been focused on the function and stability of mito-chondrial genomes. Although mitochondrial DNA is plentiful, finding mutations that exist in just a few mitochondria per tissue is the proverbial needle in a haystack. - Treatment: Lighting the way
- Nature Reviews Cancer 10(4):236 (2010)
The discovery of the Hippo–Salvador–Warts tumour suppressor pathway in Drosophila melanogaster added further weight to the value of using genetically tractable organisms to understand conserved complex signalling pathways in mammals. Work from four groups using D. melanogaster - Signalling: RAF complexities spark caution
- Nature Reviews Cancer 10(4):237 (2010)
The complete removal of tumours during surgery as part of cancer treatment is crucial as it affects patient survival. However, current criteria for delineating tumour margins are often subjective and difficult to quantify. - Cancer epigenetics: Long-range silencing
- Nature Reviews Cancer 10(4):238 (2010)
Several RAF inhibitors are in clinical trials, but three recently published papers indicate that the function of the RAS pathway in a patient's tumour will need to be assessed to avoid potential tumour-promoting effects of these inhibitors.Although ATP-competitive RAF inhibitors are active against tumours with mutant, constitutively active BRAF(V600E), which generally do not harbour activating RAS mutations, they do not suppress the growth of tumours with mutant RAS or wild-type BRAF. - Tumour suppressors: A new role for Dok
- Nature Reviews Cancer 10(4):238 (2010)
During tumorigenesis genes can be silenced by both genetic and epigenetic mechanisms. The recent creation of a prostate cancer epigenome map indicates that long-range epigenetic silencing commonly occurs in prostate cancer, and suggests that the epigenetic repression of large regions of the genome might be important for cancer initiation and progression. - In brief: Metastasis, Leukaemogenesis
- Nature Reviews Cancer 10(4):238 (2010)
A region of chromosome 8 that has been proposed to contain one or more tumour suppressors is frequently deleted in lung adenocarcinomas. Pier Paolo Pandolfi and colleagues now show that downstream of tyrosine kinase 2 (DOK2), which localizes to chromosome 8, is a tumour suppressor that is frequently lost in human lung adenocarcinoma. - Glioblastoma: Recurrence blocked
- Nature Reviews Cancer 10(4):239 (2010)
An oncogene–tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-κB Min , J.et al. Nature Med.14 Feb 2010 (doi:10.1038/nm.2100) - Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents
Sharma SV Haber DA Settleman J - Nature Reviews Cancer 10(4):241 (2010)
Glioblastoma multiforme (GBM) is treated with radiotherapy, but the majority of tumours recur. One explanation for GBM recurrence is that circulating endothelial or bone marrow cells could recreate the tumour vasculature (a process termed vasculogenesis) following irradiation, allowing any surviving tumour cells to grow. - Translational control in cancer
Silvera D Formenti SC Schneider RJ - Nature Reviews Cancer 10(4):254 (2010)
Efforts to discover new cancer drugs and predict their clinical activity are limited by the fact that laboratory models to test drug efficacy do not faithfully recapitulate this complex disease. One important model system for evaluating candidate anticancer agents is human tumour-derived cell lines. Although cultured cancer cells can exhibit distinct properties compared with their naturally growing counterparts, recent technologies that facilitate the parallel analysis of large panels of such lines, together with genomic technologies that define their genetic constitution, have revitalized efforts to use cancer cell lines to assess the clinical utility of new investigational cancer drugs and to discover predictive biomarkers. - Targeting metabolic transformation for cancer therapy
Tennant DA Durán RV Gottlieb E - Nature Reviews Cancer 10(4):267 (2010)
Remarkable progress has been made in defining a new understanding of the role of mRNA translation and protein synthesis in human cancer. Translational control is a crucial component of cancer development and progression, directing both global control of protein synthesis and selective translation of specific mRNAs that promote tumour cell survival, angiogenesis, transformation, invasion and metastasis. Translational control of cancer is multifaceted, involving alterations in translation factor levels and activities unique to different types of cancers, disease stages and the tumour microenvironment. Several clinical efforts are underway to target specific components of the translation apparatus or unique mRNA translation elements for cancer therapeutics. - The regulatory crosstalk between kinases and proteases in cancer
López-Otín C Hunter T - Nature Reviews Cancer 10(4):278 (2010)
Cancer therapy has long relied on the rapid proliferation of tumour cells for effective treatment. However, the lack of specificity in this approach often leads to undesirable side effects. Many reports have described various 'metabolic transformation' events that enable cancer cells to survive, suggesting that metabolic pathways might be good targets. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered metabolic pathways of tumours. This Review highlights pathways against which there are already drugs in different stages of development and also discusses additional druggable targets. - PARP inhibition: PARP1 and beyond
Rouleau M Patel A Hendzel MJ Kaufmann SH Poirier GG - Nature Reviews Cancer 10(4):293 (2010)
Kinases and proteases are responsible for two fundamental regulatory mechanisms — phosphorylation and proteolysis — that orchestrate the rhythms of life and death in all organisms. Recent studies have highlighted the elaborate interplay between both post-translational regulatory systems. Many intracellular or pericellular proteases are regulated by phosphorylation, whereas multiple kinases are activated or inactivated by proteolytic cleavage. The functional consequences of this regulatory crosstalk are especially relevant in the different stages of cancer progression. What are the clinical implications derived from the fertile dialogue between kinases and proteases in cancer? - MYC as a regulator of ribosome biogenesis and protein synthesis
van Riggelen J Yetil A Felsher DW - Nature Reviews Cancer 10(4):301 (2010)
Recent findings have thrust poly(ADP-ribose) polymerases (PARPs) into the limelight as potential chemotherapeutic targets. To provide a framework for understanding these recent observations, we review what is known about the structures and functions of the family of PARP enzymes, and then outline a series of questions that should be addressed to guide the rational development of PARP inhibitors as anticancer agents. - Erratum: Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer
- Nature Reviews Cancer 10(4):309 (2010)
MYC regulates the transcription of thousands of genes required to coordinate a range of cellular processes, including those essential for proliferation, growth, differentiation, apoptosis and self-renewal. Recently, MYC has also been shown to serve as a direct regulator of ribosome biogenesis. MYC coordinates protein synthesis through the transcriptional control of RNA and protein components of ribosomes, and of gene products required for the processing of ribosomal RNA, the nuclear export of ribosomal subunits and the initiation of mRNA translation. We discuss how the modulation of ribosome biogenesis by MYC may be essential to its physiological functions as well as its pathological role in tumorigenesis. - Corrigendum: Microtubules and resistance to tubulin-binding agents
- Nature Reviews Cancer 10(4):309 (2010)
In Figure 1 on page 216 of the above article, the label 'Tumour-specific antigens' was mistakenly indicated under the images of the target organs commonly involved in acute GVHD. Accordingly, this label has now been removed.
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