Hot off the presses! Feb 01

The Feb 01 issue of the is now up on Pubget (About ): 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
  - Nature Reviews Cancer 10(2):77 (2010)
  As our knowledge of tumour development grows, our interpretations of the best methods for treating this heterogeneous disease also evolve. This is undoubtedly true for the diagnosis and treatment of oesophageal adenocarcinoma.
• Wildlife cancer: The details are not so devilish
  - Nature Reviews Cancer 10(2):79 (2010)
  Devil facial tumour disease (DFTD) is a fatal cancer that affects the Tasmanian devil (Sarcophilus harrisii), an endangered species that is predicted to be extinct in 25–35 years as a result of DFTD. DFTD is thought to be a transmissible allograft tumour of neuroendocrine origin, but little is known about its biology.
• Systems biology: Network spreading
  - Nature Reviews Cancer 10(2):80 (2010)
  High-grade gliomas, such as glioblastoma, are incurable partly because the tumour cells are widely disseminated throughout the brain. This capacity for invasive growth has been associated with the expression of genes more commonly transcribed in mesenchymal cells.
• Metastasis: Motion capture
  - Nature Reviews Cancer 10(2):80 (2010)
  The ever more complex story of p53 and its relations took an interesting turn as the decade drew to a close. The function of mutant p53 proteins during tumour development is a hotly debated topic and a recent publication in Cell indicates that invasion, integrins and receptor recycling are all important to the tale.
• Cancer code cracked?
  - Nature Reviews Cancer 10(2):80 (2010)
  The entire genome sequences of two individual cancers — one small-cell lung cancer and one melanoma — have revealed the staggering number of mutations present in tumour cells compared with normal cells from the same patient.The research, published in Nature, was led by Peter Campbell, Michael Stratton and Andrew Futreal at the Wellcome Trust Sanger Institute, UK.
• In brief: Therapy, Genomic instability, Lymphoma, Tumorigenesis
  - Nature Reviews Cancer 10(2):81 (2010)
  Novel mutant-selective EGFR kinase inhibitors against EGFR T790M Zhou, W.et al. Nature 462, 1070–1074 (2009)Strategies to inhibit mutant epidermal growth factor receptor (EGFR) in non-small-cell lung cancer have been limited by the development of drug-resistant mutations, including the T790M mutation, and toxicity caused by inhibition of wild-type EGFR.
• Computational biology: Mutual ties
  - Nature Reviews Cancer 10(2):82 (2010)
  Advances in sequencing and microarray technologies are providinga wealth of cancer genome and gene expression data. However, discovering the perturbed underlying networks remains a formidable challenge for cancer biology.
• DNA damage response: DNA takes a break with SUMO
  - Nature Reviews Cancer 10(2):82 (2010)
  During the DNA damage response (DDR), repair proteins such as the E3 ubiquitin ligase BRCA1 accumulate at DNA double-stranded breaks (DSBs), and ubiquitylation at these sites helps recruit further repair proteins. Small ubiquitin-related modifier (SUMO) — which is attached to proteins by a pathway involving the E1 enzyme SAE1, the E2 enzyme UBC9 (also known as UBE21) and an E3 ligase (such as PIAS1 and PIAS4) — has also been implicated in the DDR, but its role was unclear.
• Lymphomagenesis: Far, far away
  - Nature Reviews Cancer 10(2):83 (2010)
  Translocations involving the immunoglobulin heavy chain (Igh) locus and Myc are oncogenic, but the elements that are involved in activating the transcription of these fusion genes have not been resolved. Fred Alt, Monica Gostissa and colleagues have used mouse models to show that the Igh 3′ regulatory region (Igh3′ RR) can function over long distances to activate the transcription of translocated Myc.
• Genome architecture: Reliable repositioning in cancer
  - Nature Reviews Cancer 10(2):84 (2010)
  One of the biggest challenges in cancer is proper diagnosis in the smallest possible amounts of tissue, such as that from a core needle biopsy in potential breast cancer cases. Routine protocols now in place generally rely on the opinion of a trained cytopathologist and have not been automated with any quantifiable assay.
• Senescence: A key role for CDK2
  - Nature Reviews Cancer 10(2):84 (2010)
  Oncogenes such as KRAS and MYC promote growth, but their expression can also induce apoptosis or cellular senescence. Two papers reveal that cyclin-dependent kinase 2 (CDK2) both suppresses the induction of senescence by MYC and phosphorylates MYC to bypass Ras-induced senescence.
• Angiogenesis: Regulating vessel size
  - Nature Reviews Cancer 10(2):85 (2010)
  Angiogenesis is a crucial step in tumour progression and is therefore an attractive target for therapeutic intervention. However, dissecting the role of angiogenesis genes in disease in vivo can be challenging as knockouts of many of these genes are embryonic lethal.
• Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis
  - Nature Reviews Cancer 10(2):87 (2010)
  The public health importance of Barrett's oesophagus lies in its association with oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma has risen at an alarming rate over the past four decades in many regions of the Western world, and there are indications that the incidence of this disease is on the rise in Asian populations in which it has been rare. Much has been learned of host and environmental risk factors that affect the incidence of oesophageal adenocarcinoma, and data indicate that patients with Barrett's oesophagus rarely develop oesophageal adenocarcinoma. Given that 95% of oesophageal adenocarcinomas arise in individuals without a prior diagnosis of Barrett's oesophagus, what strategies can be used to reduce late diagnosis of oesophageal adenocarcinoma?
• Mitotic chromosomal instability and cancer: mouse modelling of the human disease
  - Nature Reviews Cancer 10(2):102 (2010)
  The stepwise progression from an early dysplastic lesion to full-blown metastatic malignancy is associated with increases in genomic instability. Mitotic chromosomal instability — the inability to faithfully segregate equal chromosome complements to two daughter cells during mitosis — is a widespread phenomenon in solid tumours that is thought to serve as the fuel for tumorigenic progression. How chromosome instability (CIN) arises in tumours and what consequences it has are still, however, hotly debated issues. Here we review the recent literature with an emphasis on models that recapitulate observations from human disease.
• Fibroblast growth factor signalling: from development to cancer
  - Nature Reviews Cancer 10(2):116 (2010)
  Fibroblast growth factors (FGFs) and their receptors control a wide range of biological functions, regulating cellular proliferation, survival, migration and differentiation. Although targeting FGF signalling as a cancer therapeutic target has lagged behind that of other receptor tyrosine kinases, there is now substantial evidence for the importance of FGF signalling in the pathogenesis of diverse tumour types, and clinical reagents that specifically target the FGFs or FGF receptors are being developed. Although FGF signalling can drive tumorigenesis, in different contexts FGF signalling can mediate tumour protective functions; the identification of the mechanisms that underlie these differential effects will be important to understand how FGF signalling can be most appropriately therapeutically targeted.
• Targeting the cancer kinome through polypharmacology
  - Nature Reviews Cancer 10(2):130 (2010)
  Kinase inhibitors are the largest class of new cancer drugs. However, it is already apparent that most tumours can escape from the inhibition of any single kinase. If it is necessary to inhibit multiple kinases, how do we choose which ones? In this Opinion article, we discuss some of the strategies that are currently being used to identify new therapeutic combinations of kinase targets.
• Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors
  - Nature Reviews Cancer 10(2):138 (2010)
  The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an 'angiocrine' mechanism by producing stem and progenitor cell-active trophogens. Identification of endothelial-derived instructive angiocrine factors will allow direct tumour targeting, while diminishing the unwanted side effects associated with the use of anti-angiogenic agents.
• ABC transporters in cancer: more than just drug efflux pumps
  - Nature Reviews Cancer 10(2):147 (2010)
  Multidrug transporter proteins are best known for their contributions to chemoresistance through the efflux of anticancer drugs from cancer cells. However, a considerable body of evidence also points to their importance in cancer extending beyond drug transport to fundamental roles in tumour biology. Currently, much of the evidence for these additional roles is correlative and definitive studies are needed to confirm causality. We propose that delineating the precise roles of these transporters in tumorigenesis and treatment response will be important for the development of more effective targeted therapies.
• Correspondence: Parallel progression of tumour and metastases
  - Nature Reviews Cancer 10(2):156 (2010)
  The Opinion article (Parallel progression of primary tumours and metastases. Nature Rev. Cancer. 9, 302–312 (2009)
• Correspondence: Tumour cell dissemination and growth of metastasis
  - Nature Reviews Cancer 10(2):156 (2010)
  I am grateful for the letter of S. Koscielny and M.

Hot off the presses! May 01 Nature Reviews Cancer

The May 01 issue of the Nature Reviews Cancer is now up on Pubget (About Nature Reviews 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
  - 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.

Hot off the presses! Apr 01 Nature Reviews Cancer

The Apr 01 issue of the Nature Reviews Cancer is now up on Pubget (About Nature Reviews 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
  - Nature Reviews Cancer 10(3):157 (2010)
  How long is it since you last had to solve an equation? Most biologists have happily forgotten about these beasts since their move to the microscope or Petri dish, but mathematics is becoming an essential partner in cancer research as we move forwards into a new decade.
• Tumorigenesis: Bad neighbours
  - Nature Reviews Cancer 10(3):159 (2010)
  Human tumours have a high degree of cellular and genetic heterogeneity, and the mechanisms by which distinct mutations in different cellular clones may cooperate to promote tumorigenesis are unclear. Xu and colleagues present evidence that a two-tier mechanism involving Jun N-terminal kinase (JNK) and Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signalling enables interclonal cooperation between RasG12V and scribbled (scrib) mutations in Drosophila melanogaster.
• Lipidomics: Growing on a free-fat diet
  - Nature Reviews Cancer 10(3):160 (2010)
  Heightened lipogenesis, a common metabolic signature of malignant cells, is thought to promote pathology by generating substrates for energy production and membrane synthesis, as well as signalling lipids that trigger pro-tumorigenic cascades. However, newly synthesized fatty acids are quickly incorporated into lipid stores and so it is unclear how they are made available for cellular functions.
• Therapeutics: Selective inhibitors gain traction
  - Nature Reviews Cancer 10(3):160 (2010)
  March 2010 Vol 10 No 3 * Research Highlights * Reviews * Perspectives Also this month: * Article series: Therapeutic resistance * Previous About the cover From the editors p157 | doi:10.1038/nrc2822 Research Highlights Tumorigenesis: Bad neighbours | PDF (167 KB) p159 | doi:10.1038/nrc2821 Cooperative signalling between two tumour clones expressing different oncogenic mutations is reported. Lipidomics: Growing on a free-fat diet | PDF (157 KB) p160 | doi:10.1038/nrc2811 Monoglyceride lipase levels are increased in aggressive tumours, provide the principal source of free fatty acids and increase the production of biologically active lipids. Therapeutics: Selective inhibitors gain traction | PDF (216 KB) p160 | doi:10.1038/nrc2814 A selective TORC1 and TORC2 active site inhibitor has high efficacy and tolerability in models of acute leukaemia. Genetics: Back to the blueprint | PDF (190 KB) p161 | doi:10.1038/nrc2810 Four recent papers detail changes in the cancer genome. Genome instability: Forbidden CIN | PDF (215 KB) p162 | doi:10.1038/nrc2813 New insight into how Bub1 and BUBR1 prevent chromosomal instability. Tumour microenvironment: Macrophages lead the way | PDF (236 KB) p162 | doi:10.1038/nrc2816 A paracrine signalling pathway between tumour cells and tumour-associated macrophages has been characterized. Stem cells: Insights into breast cancer heterogeneity | PDF (312 KB) p163 | doi:10.1038/nrc2815 The proportion of cancer stem cells might underpin differencies between poorly and well-differentiated breast cancers. Reviews Eph receptors and ephrins in cancer: bidirectional signalling and beyond Elena B. Pasquale p165 | doi:10.1038/nrc2806 Accumulating evidence implicates the deregulation of Eph–ephrin signalling in cancer pathogenesis. Bidirectional signalling and context-dependent effects allow the Eph–ephrin system to have complex and contrasting effects on tumours. There is still much to be learned about this system in cancer, but it is nevertheless emerging as a therapeutic target. * Abstract * Full Text * PDF (633 KB) Eicosanoids and cancer Dingzhi Wang & Raymond N. DuBois p181 | doi:10.1038/nrc2809 Eicosanoids, including prostaglandins and leukotrienes, are biologically active lipids that have been implicated in inflammation and cancer. This Review highlights the roles of eicosanoids in tumours and their microenvironment, and how their signalling pathways might be exploited to develop more effective cancer chemopreventive and/or therapeutic agents. * Abstract * Full Text * PDF (676 KB) Article series: Therapeutic resistance Microtubules and resistance to tubulin-binding agents Maria Kavallaris p194 | doi:10.1038/nrc2803 Microtubules are dynamic structures composed of α–β-tubulin heterodimers that are important targets for tubulin-binding agents such as paclitaxel. Mutation or aberrant expression of specific β-tubulin isotypes and changes to microtubule-regulating proteins are associated with resistance to these drugs. Understanding the molecular mechanisms that mediate this resistance will be vital to improve the efficacy of these agents. * Abstract * Full Text * PDF (605 KB) Perspectives Opinion Breast and prostate cancer: more similar than different Gail P. Risbridger, Ian D. Davis, Stephen N. Birrell & Wayne D. Tilley p205 | doi:10.1038/nrc2795 This Opinion article discusses some key similarities between breast and prostate cancer, with a focus on hormone and hormone receptor involvement. Understanding the commonalities between these cancers will hopefully provide unique opportunities for therapy. * Abstract * Full Text * PDF (346 KB) Timeline Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer Robert R. Jenq & Marcel R. M. van den Brink p213 | doi:10.1038/nrc2804 This Timeline article looks back over 50 years of haematopoietic stem cell transplantation as a cancer therapy, highlighting the substantial advances that have been made to increase the specificity of this treatment for cancer cells, as well as improvements in availability, safety and patient outcomes. * Abstract * Full Text * PDF (949 KB) Timeline Dissecting cancer through mathematics: from the cell to the animal model Helen M. Byrne p221 | doi:10.1038/nrc2808 This Timeline article charts progress in mathematical modelling of cancer over the past 50 years, highlighting the different theoretical approaches that have been used to dissect the disease and the insights that have arisen. * Abstract * Full Text * PDF (636 KB) * Supplementary information Corrigendum: Leukaemogenesis: more than mutant genes Jianjun Chen, Olatoyosi Odenike & Janet D. Rowley p230 | doi:10.1038/nrc2807 * Full Text * PDF (115 KB)
• Genetics: Back to the blueprint
  - Nature Reviews Cancer 10(3):161 (2010)
  A great deal of evidence points to the crucial role of mTOR in several human malignancies, perhaps reflecting its regulation by upstream oncogenic PI3K signalling pathways and its regulation of downstream cell growth, survival and proliferation pathways. mTOR can form two complexes, mTOR complex 1 (TORC1) and TORC2.
• Genome instability: Forbidden CIN
  - Nature Reviews Cancer 10(3):162 (2010)
  The rapid advance of DNA sequencing techniques means that it is now possible to find most of the somatic changes that have occurred during the evolution of a specific type of tumour. Four papers recently published in Nature provide more insight into genetic changes that occur in lung, breast, renal and skin cancers.
• Tumour microenvironment: Macrophages lead the way
  - Nature Reviews Cancer 10(3):162 (2010)
  Aberrant mitosis results in chromo-somal instability (CIN; the gain or loss of whole or large fragments of chromosomes), which is the major form of cancer genome instability. Two papers provide new insight into how the yeast Bub1 and Drosophila melanogaster BUB1-related (BUBR1) kinases help to ensure accurate chromosome separation and prevent CIN.
• Stem cells: Insights into breast cancer heterogeneity
  - Nature Reviews Cancer 10(3):163 (2010)
  Tumour-associated macrophages (TAMs) are known to be an important component of the tumour microenvironment and can promote tumour progression, but the mechanisms are poorly understood. Johanna Joyce and colleagues have now characterized a paracrine signalling pathway between tumour cells and TAMs.
• Eph receptors and ephrins in cancer: bidirectional signalling and beyond
  Pasquale EB - Nature Reviews Cancer 10(3):165 (2010)
  Increasing evidence indicates that breast tumours are sustained by a population of cancer stem cells (CSCs). In a recent study published in Cell, researchers led by Pier Paolo Di Fiore report the purification and molecular characterization of normal human mammary stem cells (hNMSCs) from cultured mammospheres, and provide evidence supporting a model in which breast tumour heterogeneity is a reflection of the number of CSC-like cells in the tumour.
• Eicosanoids and cancer
  Wang D Dubois RN - Nature Reviews Cancer 10(3):181 (2010)
  The Eph receptor tyrosine kinases and their ephrin ligands have intriguing expression patterns in cancer cells and tumour blood vessels, which suggest important roles for their bidirectional signals in many aspects of cancer development and progression. Eph gene mutations probably also contribute to cancer pathogenesis. Eph receptors and ephrins have been shown to affect the growth, migration and invasion of cancer cells in culture as well as tumour growth, invasiveness, angiogenesis and metastasis in vivo. However, Eph signalling activities in cancer seem to be complex, and are characterized by puzzling dichotomies. Nevertheless, the Eph receptors are promising new therapeutic targets in cancer.
• Microtubules and resistance to tubulin-binding agents
  Kavallaris M - Nature Reviews Cancer 10(3):194 (2010)
  Eicosanoids, including prostaglandins and leukotrienes, are biologically active lipids that have been implicated in various pathological processes, such as inflammation and cancer. This Review highlights our understanding of the intricate roles of eicosanoids in epithelial-derived tumours and their microenvironment. The knowledge of how these lipids orchestrate the complex interactions between transformed epithelial cells and the surrounding stromal cells is crucial for understanding tumour evolution, progression and metastasis. Understanding the molecular mechanisms underlying the role of prostaglandins and other eicosanoids in cancer progression will help to develop more effective cancer chemopreventive and/or therapeutic agents.
• Breast and prostate cancer: more similar than different
  Risbridger GP Davis ID Birrell SN Tilley WD - Nature Reviews Cancer 10(3):205 (2010)
  Microtubules are dynamic structures composed of α–β-tubulin heterodimers that are essential in cell division and are important targets for cancer drugs. Mutations in β-tubulin that affect microtubule polymer mass and/or drug binding are associated with resistance to tubulin-binding agents such as paclitaxel. The aberrant expression of specific β-tubulin isotypes, in particular βIII-tubulin, or of microtubule-regulating proteins is important clinically in tumour aggressiveness and resistance to chemotherapy. In addition, changes in actin regulation can also mediate resistance to tubulin-binding agents. Understanding the molecular mechanisms that mediate resistance to tubulin-binding agents will be vital to improve the efficacy of these agents.
• Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer
  Jenq RR van den Brink MR - Nature Reviews Cancer 10(3):213 (2010)
  Breast cancer and prostate cancer are the two most common invasive cancers in women and men, respectively. Although these cancers arise in organs that are different in terms of anatomy and physiological function both organs require gonadal steroids for their development, and tumours that arise from them are typically hormone-dependent and have remarkable underlying biological similarities. Many of the recent advances in understanding the pathophysiology of breast and prostate cancers have paved the way for new treatment strategies. In this Opinion article we discuss some key issues common to breast and prostate cancer and how new insights into these cancers could improve patient outcomes.
• Dissecting cancer through mathematics: from the cell to the animal model
  Byrne HM - Nature Reviews Cancer 10(3):221 (2010)
  The year 2009 marked the fiftieth anniversary of the first successful allogeneic haematopoietic stem cell transplant (HSCT). The field of HSCT has pioneered some of the most exciting areas of research today. HSCT was the original stem cell therapy, the first cancer immune therapy and the earliest example of individualized cancer therapy. In this Timeline article we review the history of the development of HSCT and major advances made in the past 50 years. We highlight accomplishments made by researchers who continue to strive to improve outcomes for patients and increase the availability of this potentially life-saving therapy for patients with otherwise incurable malignancies.
• Corrigendum: Leukaemogenesis: more than mutant genes
  - Nature Reviews Cancer 10(3):230 (2010)
  This Timeline article charts progress in mathematical modelling of cancer over the past 50 years, highlighting the different theoretical approaches that have been used to dissect the disease and the insights that have arisen. Although most of this research was conducted with little involvement from experimentalists or clinicians, there are signs that the tide is turning and that increasing numbers of those involved in cancer research and mathematical modellers are recognizing that by working together they might more rapidly advance our understanding of cancer and improve its treatment.

Hot off the presses! May 01 Nature Reviews Immunology

The May 01 issue of the Nature Reviews Immunology is now up on Pubget (About Nature Reviews Immunology): 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
  - Nature Reviews Immunology 10(5):285 (2010)
  In this issue, we present a series of comprehensive Review, Perspective and Comment articles on the field of therapeutic antibodies, highlighting the recent advances and future challenges for their development and use in the treatment of cancer, autoimmunity and infectious diseases.Georges Köhler and César Milstein first described the hybridoma technique for the production of monoclonal antibodies in 1975, a discovery that revolutionized science and medicine.
• Innate immunity: Ready, AIM, fire!
  - Nature Reviews Immunology 10(5):287 (2010)
  Reporting in Nature Immunology, two independent groups of researchers provide the first genetic evidence that the DNA sensor AIM2 (absent in melanoma 2) is crucial for immunity against certain bacterial infections and DNA viruses.AIM2 was recently identified as a cytoplasmic receptor that recognizes double-stranded DNA and assembles with the caspase 1-activating adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) to form the AIM2 inflammasome.
• Viral immunity: How CMV bypasses immune memory
  - Nature Reviews Immunology 10(5):288 (2010)
  Persistent infection with cytomegalovirus (CMV) induces high-frequency CMV-specific T cell responses and high titres of neutralizing antibodies, but this immune response cannot prevent superinfection with another strain of CMV. A study published in Science now explains the mechanism behind this ability of secondary CMV infections to evade immune memory.
• Immune regulation: Tidy TIM
  - Nature Reviews Immunology 10(5):288 (2010)
  The T cell immunoglobulin domain and mucin domain family member TIM4 (also known as TIMD4) is expressed by macrophages and dendritic cells (DCs) and binds to both phosphatidylserine on apoptotic cells and to TIM1 (also known as TIMD1) on activated T cells. TIM4 has been attributed with both activating and inhibitory immune functions but its predominant role in vivo has remained unclear.
• T cell responses: IL-2 overrules tolerogenic liver responses
  - Nature Reviews Immunology 10(5):289 (2010)
  Antigen-presenting cells (APCs) in the liver generally induce T cell tolerance rather than T cell immunity. Of the APCs in the liver, liver sinusoidal endothelial cells (LSECs) are highly adept at taking up soluble antigens from the blood and cross-presenting these antigens on MHC class I molecules to passing naive CD8+ T cells.
• Immune tolerance: New peacekeepers identified
  - Nature Reviews Immunology 10(5):290 (2010)
  Lymph node stromal cells (LNSCs) have been shown to be mediators of antigen-specific peripheral T cell tolerance through the expression of peripheral tissue antigens (PTAs). However, the specific cell subsets involved were not known.
• Scientific basis for 'man flu'
  - Nature Reviews Immunology 10(5):290 (2010)
  Men may have weaker immune systems than women and suffer disease more seriously and for longer, say scientists at the University of Cambridge, UK. The study, published in the Proceedings of the Royal Society B: Biological Sciences (24 Mar 2010), gives scientific credence to the phenomenon colloquially referred to as 'man flu' and suggests that "Maybe men aren't just playing sick, but really are more susceptible" (The Times, 24 Mar 2010).
• Innate immunity: Toll tremors
  - Nature Reviews Immunology 10(5):291 (2010)
  Epilepsy is a chronic neurological disorder in which affected individuals suffer from recurring, unprovoked seizures. There is evidence to suggest that inflammatory processes can promote seizures, and damage to the brain following neurotrauma, stroke or infection is associated with a high risk of developing epilepsy.
• In brief: Therapeutic antibodies, Therapeutic antibodies, Therapeutic antibodies
  - Nature Reviews Immunology 10(5):291 (2010)
  Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce β-chemokines Moody , M. A.et al. J. Exp. Med. 207, 763–776 (2010)
• Tumour immunology: Promoting tolerance
  - Nature Reviews Immunology 10(5):292 (2010)
  Tumour cells can promote their survival by shifting the host immune response from immunogenic to tolerogenic. Swartz and colleagues have shown that tumours can do this by exploiting a pathway that is normally involved in maintaining tolerance in the lymph node stroma.
• In brief: Autoimmunity, Regulatory T cells, Innate immunity
  - Nature Reviews Immunology 10(5):292 (2010)
  T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis Axtell , R. C.et al. Nature Med. 16, 406–412 (2010)
• Mucosal immunology: Inflammasome activation in the gut
  - Nature Reviews Immunology 10(5):293 (2010)
  Innate immune signalling pathways triggered by commensal bacteria have an important role in maintaining homeostasis in the gut. However, excessive inflammation is known to contribute to the development of colitis and colitis-associated colorectal cancer.
• Therapeutic antibodies: past, present and future
  - Nature Reviews Immunology 10(5):297 (2010)
  Over the past 10 years, the market for monoclonal antibodies has grown exponentially. This focus issue brings together articles on the basic biology of antibodies and their therapeutic use, providing an overview of the latest prospects and continued challenges for the development of safe, efficient and affordable therapeutic antibodies.
• Comment: Can primary immunodeficiencies help to provide insights into infectious risks of therapeutic antibodies?
  - Nature Reviews Immunology 10(5):299 (2010)
  Patients treated with monoclonal antibodies directed against immunological molecules may be viewed as being similar to patients with primary immunodeficiency (PID) of the corresponding antibody target, with regards to infectious risk. László Maródi and Jean-Laurent Casanova propose that the natural history of PIDs might indicate which infectious diseases should be monitored in patients receiving therapeutic antibodies.
• Therapeutic antibodies for autoimmunity and inflammation
  Chan AC Carter PJ - Nature Reviews Immunology 10(5):301 (2010)
  The development of therapeutic antibodies has evolved over the past decade into a mainstay of therapeutic options for patients with autoimmune and inflammatory diseases. Substantial advances in understanding the biology of human diseases have been made and tremendous benefit to patients has been gained with the first generation of therapeutic antibodies. The lessons learnt from these antibodies have provided the foundation for the discovery and development of future therapeutic antibodies. Here we review how key insights obtained from the development of therapeutic antibodies complemented by newer antibody engineering technologies are delivering a second generation of therapeutic antibodies with promise for greater clinical efficacy and safety.
• Monoclonal antibodies: versatile platforms for cancer immunotherapy
  Weiner LM Surana R Wang S - Nature Reviews Immunology 10(5):317 (2010)
  Antibodies are important therapeutic agents for cancer. Recently, it has become clear that antibodies possess several clinically relevant mechanisms of action. Many clinically useful antibodies can manipulate tumour-related signalling. In addition, antibodies exhibit various immunomodulatory properties and, by directly activating or inhibiting molecules of the immune system, antibodies can promote the induction of antitumour immune responses. These immunomodulatory properties can form the basis for new cancer treatment strategies.
• FcγRIIB in autoimmunity and infection: evolutionary and therapeutic implications
  Smith KG Clatworthy MR - Nature Reviews Immunology 10(5):328 (2010)
  FcγRIIB is the only inhibitory Fc receptor. It controls many aspects of immune and inflammatory responses, and variation in the gene encoding this protein has long been associated with susceptibility to autoimmune disease, particularly systemic lupus erythematosus (SLE). FcγRIIB is also involved in the complex regulation of defence against infection. A loss-of-function polymorphism in FcγRIIB protects against severe malaria, the investigation of which is beginning to clarify the evolutionary pressures that drive ethnic variation in autoimmunity. Our increased understanding of the function of FcγRIIB also has potentially far-reaching therapeutic implications, being involved in the mechanism of action of intravenous immunoglobulin, controlling the efficacy of monoclonal antibody therapy and providing a direct therapeutic target.
• Strategies and challenges for the next generation of therapeutic antibodies
  Beck A Wurch T Bailly C Corvaia N - Nature Reviews Immunology 10(5):345 (2010)
  Antibodies and related products are the fastest growing class of therapeutic agents. By analysing the regulatory approvals of IgG-based biotherapeutic agents in the past 10 years, we can gain insights into the successful strategies used by pharmaceutical companies so far to bring innovative drugs to the market. Many challenges will have to be faced in the next decade to bring more efficient and affordable antibody-based drugs to the clinic. Here, we discuss strategies to select the best therapeutic antigen targets, to optimize the structure of IgG antibodies and to design related or new structures with additional functions.
• Dynamic imaging of host–pathogen interactions in vivo
  Coombes JL Robey EA - Nature Reviews Immunology 10(5):353 (2010)
  In the past decade, advances in microscopic imaging methods, together with the development of genetically encoded fluorescent reporters, have made it possible to directly visualize the behaviour of cells in living tissues. At the same time, immunologists have been turning their attention from the traditional focus on responses to model antigens to a new focus on in vivo infection models. Recently, these two trends have intersected with exciting results. Here we discuss how dynamic imaging of in vivo infection has revealed fascinating and unexpected details of host–pathogen interactions at a new level of spatial and temporal resolution.
• Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells
  Glass CK Saijo K - Nature Reviews Immunology 10(5):365 (2010)
  Members of the nuclear receptor superfamily of ligand-dependent transcription factors regulate diverse aspects of immunity and inflammation by both positively and negatively regulating gene expression. Here, we review recent studies providing insights into the distinct mechanisms that enable nuclear receptors to antagonize pro-inflammatory programmes of gene expression in macrophages and T cells by altering the turnover or recruitment of co-repressors and co-activators in a gene-specific manner. These nuclear receptor-dependent transrepression pathways are proposed to have roles in controlling the initiation, magnitude and duration of pro-inflammatory gene expression and are amenable to pharmacological manipulation.

Hot off the presses! Feb 01

The Feb 01 issue of the is now up on Pubget (About ): 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:

• 
  - Nature reviews. Molecular cell biology 11(2):83 (2010)
  Life is complex, even for a eukaryotic cell. For example, whenever a cell divides and gives rise to two daughter cells, it must faithfully duplicate its genome, ensure that the two resulting genome copies are correctly distributed to the daughter cells and then complete the cell cycle by dividing the cytoplasm through cytokinesis.
• DNA damage response: DNA takes a break with SUMO | PDF (225 KB)
  - Nature reviews. Molecular cell biology 11(2):85 (2010)
  PIAS1 and PIAS4 promote BRCA1 sumoylation and DNA repair.
• Lipid trafficking: Exchange by ORDer | PDF (199 KB)
  - Nature reviews. Molecular cell biology 11(2):86 (2010)
  ORPs bind two membranes simultaneously and regulate sterol transfer between them.
• Cancer biology: Motion capture | PDF (247 KB)
  - Nature reviews. Molecular cell biology 11(2):86 (2010)
  Mutant p53 promotes cell invasion through integrin recycling.
• Epigenetics: Unravelling demethylation | PDF (429 KB)
  - Nature reviews. Molecular cell biology 11(2):87 (2010)
  AID and elongator complexes are crucial for mammalian DNA demethylation.
• Cell signalling: It's good to talk | PDF (200 KB)
  - Nature reviews. Molecular cell biology 11(2):88 (2010)
  Cell-specific signalling networks during the interaction between cells.
• Endocytosis: Acetylation controls EGF traffic | PDF (209 KB)
  - Nature reviews. Molecular cell biology 11(2):88 (2010)
  The deacetylase HDAC6 regulates the endocytic trafficking of EGFR.
• Small RNAs: Size control | PDF (229 KB)
  - Nature reviews. Molecular cell biology 11(2):88 (2010)
  miR-8 positively regulates Drosophila melanogaster body size.
• Transcription | Cell cycle | Molecular motors | PDF (161 KB)
  - Nature reviews. Molecular cell biology 11(2):89 (2010)
  Transcription H2A.Z-containing nucleosomes mediate the thermosensory response in Arabidopsis Kumar, S. V. & Wigge, P. A. Cell 140, 136–147 (2010) Plant development adapts to temperature variations.
• RNA silencing sorted | PDF (182 KB)
  - Nature reviews. Molecular cell biology 11(2):90 (2010)
  Understanding the mechanism of siRNA-mediated gene silencing.
• DNA damage response: Bridging genomic instability disorders | PDF (247 KB)
  - Nature reviews. Molecular cell biology 11(2):90 (2010)
  The Fanconi anaemia protein FANCM links two genome instability disorders.
• Mechanisms of chromosome behaviour during mitosis
  - Nature reviews. Molecular cell biology 11(2):91 (2010)
  For over a century, scientists have strived to understand the mechanisms that govern the accurate segregation of chromosomes during mitosis. The most intriguing feature of this process, which is particularly prominent in higher eukaryotes, is the complex behaviour exhibited by the chromosomes. This behaviour is based on specific and highly regulated interactions between the chromosomes and spindle microtubules. Recent discoveries, enabled by high-resolution imaging combined with the various genetic, molecular, cell biological and chemical tools, support the idea that establishing and controlling the dynamic interaction between chromosomes and microtubules is a major factor in genomic fidelity.
• PKC and the control of localized signal dynamics
  - Nature reviews. Molecular cell biology 11(2):103 (2010)
  Networks of signal transducers determine the conversion of environmental cues into cellular actions. Among the main players in these networks are protein kinases, which can acutely and reversibly modify protein functions to influence cellular events. One group of kinases, the protein kinase C (PKC) family, have been increasingly implicated in the organization of signal propagation, particularly in the spatial distribution of signals. Examples of where and how various PKC isoforms direct this tier of signal organization are becoming more evident.
• The mechanism of eukaryotic translation initiation and principles of its regulation
  - Nature reviews. Molecular cell biology 11(2):113 (2010)
  Protein synthesis is principally regulated at the initiation stage (rather than during elongation or termination), allowing rapid, reversible and spatial control of gene expression. Progress over recent years in determining the structures and activities of initiation factors, and in mapping their interactions in ribosomal initiation complexes, have advanced our understanding of the complex translation initiation process. These developments have provided a solid foundation for studying the regulation of translation initiation by mechanisms that include the modulation of initiation factor activity (which affects almost all scanning-dependent initiation) and through sequence-specific RNA-binding proteins and microRNAs (which affect individual mRNAs).
• Myosin VI: an innovative motor that challenged the swinging lever arm hypothesis
  - Nature reviews. Molecular cell biology 11(2):128 (2010)
  The swinging crossbridge hypothesis states that energy from ATP hydrolysis is transduced to mechanical movement of the myosin head while bound to actin. The light chain-binding region of myosin is thought to act as a lever arm that amplifies movements near the catalytic site. This model has been challenged by findings that myosin VI takes larger steps along actin filaments than early interpretations of its structure seem to allow. We now know that myosin VI does indeed operate by an unusual ~ 180° lever arm swing and achieves its large step size using special structural features in its tail domain.
• BRCA1 and its toolbox for the maintenance of genome integrity
  Huen MS Sy SM Chen J - Nature reviews. Molecular cell biology 11(2):138 (2010)
  The breast and ovarian cancer type 1 susceptibility protein (BRCA1) has pivotal roles in the maintenance of genome stability. Studies support that BRCA1 exerts its tumour suppression function primarily through its involvement in cell cycle checkpoint control and DNA damage repair. In addition, recent proteomic and genetic studies have revealed the presence of distinct BRCA1 complexes in vivo, each of which governs a specific cellular response to DNA damage. Thus, BRCA1 is emerging as the master regulator of the genome through its ability to execute and coordinate various aspects of the DNA damage response.
• Understanding cytokinesis: lessons from fission yeast
  - Nature reviews. Molecular cell biology 11(2):149 (2010)
  For decades after the discovery that a contractile ring made of actin filaments and myosin II produces the force to constrict the cleavage furrow of animal cells, the complexity of cytokinesis has slowed progress in understanding the mechanism. Mechanistic insights, however, have been obtained by genetic, biochemical, microscopic and mathematical modelling approaches in the fission yeast Schizosaccharomyces pombe. Many features that have been identified in fission yeast are probably shared with animal cells, as both inherited many cytokinesis genes from their common ancestor about one billion years ago.