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.
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