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  • Sphingolipid metabolism in cancer signalling and therapy
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-17
    Besim Ogretmen

    Sphingolipid metabolism in cancer signalling and therapy Sphingolipid metabolism in cancer signalling and therapy, Published online: 17 November 2017; doi:10.1038/nrc.2017.96 NatureArticleSnippet(type=short-summary, markup= Sphingolipids, specifically ceramide and sphingosine-1-phosphate, have opposing roles in regulating cancer cell death and survival, respectively. This Review discusses the mechanistic and clinical studies of sphingolipid signalling and metabolism in cancer, highlighting current and emerging therapeutic strategies to target these bioactive lipids. , isJats=true)

    更新日期:2017-11-17
  • Sphingolipid metabolism in cancer signalling and therapy
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-17
    Besim Ogretmen

    Sphingolipid metabolism in cancer signalling and therapy Sphingolipid metabolism in cancer signalling and therapy, Published online: 17 November 2017; doi:10.1038/nrc.2017.96 NatureArticleSnippet(type=short-summary, markup= Sphingolipids, specifically ceramide and sphingosine-1-phosphate, have opposing roles in regulating cancer cell death and survival, respectively. This Review discusses the mechanistic and clinical studies of sphingolipid signalling and metabolism in cancer, highlighting current and emerging therapeutic strategies to target these bioactive lipids. , isJats=true)

    更新日期:2017-11-17
  • Small-cell lung cancer: what we know, what we need to know and the path forward
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-10
    Adi F. Gazdar, Paul A. Bunn, John D. Minna

    Small-cell lung cancer: what we know, what we need to know and the path forwardSmall-cell lung cancer: what we know, what we need to know and the path forward, Published online: 10 November 2017; doi:10.1038/nrc.2017.106

    更新日期:2017-11-10
  • Tumour suppressors: Digging deeper into p53's functions
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-10
    Sarah Seton-Rogers

    Tumour suppressors: Digging deeper into p53's functionsTumour suppressors: Digging deeper into p53's functions, Published online: 10 November 2017; doi:10.1038/nrc.2017.108NatureArticleSnippet(type=short-summary, markup=Mello et al. analysed the effects of various p53 transactivation domain mutants in pancreatic ductal adenocarcinoma and uncovered a crucial tumour-suppressive pathway in which p53 mediates inhibition of the transcriptional co-activator YAP., isJats=true)

    更新日期:2017-11-10
  • Tumour angiogenesis: Controlling nerves
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-10
    Ulrike Harjes

    Tumour angiogenesis: Controlling nervesTumour angiogenesis: Controlling nerves, Published online: 10 November 2017; doi:10.1038/nrc.2017.107NatureArticleSnippet(type=short-summary, markup=Sympathetic nerves associate with tumours and regulate the tumour microenvironment. How this innervation promotes tumorigenesis is unclear. A new study in Science shows that β-adrenergic signalling controls tumour growth by promoting tumour angiogenesis, through the regulation of vascular metabolism., isJats=true)

    更新日期:2017-11-10
  • Transport of drugs from blood vessels to tumour tissue
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-10
    Mark W. Dewhirst, Timothy W. Secomb

    Transport of drugs from blood vessels to tumour tissueTransport of drugs from blood vessels to tumour tissue, Published online: 10 November 2017; doi:10.1038/nrc.2017.93NatureArticleSnippet(type=short-summary, markup=This Review by Dewhirst and Secomb describes the current understanding of drug transport to tumour cells and the progress that has been made in developing methods to enhance drug delivery., isJats=true)

    更新日期:2017-11-10
  • Small-cell lung cancer: what we know, what we need to know and the path forward
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-10
    Adi F. Gazdar, Paul A. Bunn, John D. Minna

    Small-cell lung cancer: what we know, what we need to know and the path forwardSmall-cell lung cancer: what we know, what we need to know and the path forward, Published online: 10 November 2017; doi:10.1038/nrc.2017.106

    更新日期:2017-11-10
  • Tumour suppressors: Digging deeper into p53's functions
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-10
    Sarah Seton-Rogers

    Tumour suppressors: Digging deeper into p53's functionsTumour suppressors: Digging deeper into p53's functions, Published online: 10 November 2017; doi:10.1038/nrc.2017.108NatureArticleSnippet(type=short-summary, markup=Mello et al. analysed the effects of various p53 transactivation domain mutants in pancreatic ductal adenocarcinoma and uncovered a crucial tumour-suppressive pathway in which p53 mediates inhibition of the transcriptional co-activator YAP., isJats=true)

    更新日期:2017-11-10
  • Tumour angiogenesis: Controlling nerves
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-10
    Ulrike Harjes

    Tumour angiogenesis: Controlling nervesTumour angiogenesis: Controlling nerves, Published online: 10 November 2017; doi:10.1038/nrc.2017.107NatureArticleSnippet(type=short-summary, markup=Sympathetic nerves associate with tumours and regulate the tumour microenvironment. How this innervation promotes tumorigenesis is unclear. A new study in Science shows that β-adrenergic signalling controls tumour growth by promoting tumour angiogenesis, through the regulation of vascular metabolism., isJats=true)

    更新日期:2017-11-10
  • Transport of drugs from blood vessels to tumour tissue
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-10
    Mark W. Dewhirst, Timothy W. Secomb

    Transport of drugs from blood vessels to tumour tissueTransport of drugs from blood vessels to tumour tissue, Published online: 10 November 2017; doi:10.1038/nrc.2017.93NatureArticleSnippet(type=short-summary, markup=This Review by Dewhirst and Secomb describes the current understanding of drug transport to tumour cells and the progress that has been made in developing methods to enhance drug delivery., isJats=true)

    更新日期:2017-11-10
  • Preclinical mouse solid tumour models: status quo, challenges and perspectives
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-10-27
    Nicolas Gengenbacher, Mahak Singhal, Hellmut G. Augustin

    Oncology research in humans is limited to analytical and observational studies for obvious ethical reasons, with therapy-focused clinical trials being the one exception to this rule. Preclinical mouse tumour models therefore serve as an indispensable intermediate experimental model system bridging more reductionist in vitro research with human studies. Based on a systematic survey of preclinical mouse tumour studies published in eight scientific journals in 2016, this Analysis provides an overview of how contemporary preclinical mouse tumour biology research is pursued. It thereby identifies some of the most important challenges in this field and discusses potential ways in which preclinical mouse tumour models could be improved for better relevance, reproducibility and translatability.

    更新日期:2017-10-30
  • Metabolism: More lactate, please
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-10-27
    Ulrike Harjes

    Metabolism: More lactate, please Nature Reviews Cancer, Published online: 27 October 2017; doi:10.1038/nrc.2017.101 The importance of 'Warburgian' metabolism in cancer is an increasingly disputed topic. By studying cancer metabolism in patients and mouse models, Faubert et al. now show that lactate is used as a respiratory fuel in non-small-cell lung cancer in vivo.

    更新日期:2017-10-30
  • Small-cell lung cancer: what we know, what we need to know and the path forward
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-10-27
    Adi F. Gazdar, Paul A. Bunn, John D. Minna

    Small-cell lung cancer (SCLC) is a deadly tumour accounting for approximately 15% of lung cancers and is pathologically, molecularly, biologically and clinically very different from other lung cancers. While the majority of tumours express a neuroendocrine programme (integrating neural and endocrine properties), an important subset of tumours have low or absent expression of this programme. The probable initiating molecular events are inactivation of TP53 and RB1, as well as frequent disruption of several signalling networks, including Notch signalling. SCLC, when diagnosed, is usually widely metastatic and initially responds to cytotoxic therapy but nearly always rapidly relapses with resistance to further therapies. There were no important therapeutic clinical advances for 30 years, leading SCLC to be designated a 'recalcitrant cancer'. Scientific studies are hampered by a lack of tissue availability. However, over the past 5 years, there has been a worldwide resurgence of studies on SCLC, including comprehensive molecular analyses, the development of relevant genetically engineered mouse models and the establishment of patient-derived xenografts. These studies have led to the discovery of new potential therapeutic vulnerabilities for SCLC and therefore to new clinical trials. Thus, while the past has been bleak, the future offers greater promise.

    更新日期:2017-10-30
  • Cancer models: Escaping those primitive origins
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-10-27
    Anna Dart

    Cancer models: Escaping those primitive origins Nature Reviews Cancer, Published online: 27 October 2017; doi:10.1038/nrc.2017.100 An embryonic avian model recapitulates the early stages of tumorigenesis and metastases seen in patients with neuroblastoma.

    更新日期:2017-10-30
  • Targeted therapies: Understanding tumour drug addiction
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-01
    Conor A. Bradley

    Targeted therapies: Understanding tumour drug addiction Nature Reviews Cancer, Published online: 25 October 2017; doi:10.1038/nrc.2017.98 Kong et al. report a mechanism that underlies tumour 'drug addiction' in melanoma cell lines and mouse models involving an ERK2-dependent phenotype switch, which might have clinical implications for the use of alternating treatment strategies with targeted therapies.

    更新日期:2017-10-30
  • Understanding and targeting resistance mechanisms in NSCLC
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-01
    Julia Rotow, Trever G. Bivona

    The expanding spectrum of both established and candidate oncogenic driver mutations identified in non-small-cell lung cancer (NSCLC), coupled with the increasing number of clinically available signal transduction pathway inhibitors targeting these driver mutations, offers a tremendous opportunity to enhance patient outcomes. Despite these molecular advances, advanced-stage NSCLC remains largely incurable due to therapeutic resistance. In this Review, we discuss alterations in the targeted oncogene ('on-target' resistance) and in other downstream and parallel pathways ('off-target' resistance) leading to resistance to targeted therapies in NSCLC, and we provide an overview of the current understanding of the bidirectional interactions with the tumour microenvironment that promote therapeutic resistance. We highlight common mechanistic themes underpinning resistance to targeted therapies that are shared by NSCLC subtypes, including those with oncogenic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS1 proto-oncogene receptor tyrosine kinase (ROS1), serine/threonine-protein kinase b-raf (BRAF) and other less established oncoproteins. Finally, we discuss how understanding these themes can inform therapeutic strategies, including combination therapy approaches, and overcome the challenge of tumour heterogeneity.

    更新日期:2017-10-30
  • Targeting immunosuppressive adenosine in cancer
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-10-23
    Dipti Vijayan, Arabella Young, Michele W.L. Teng, Mark J. Smyth

    Despite the success of anti-programmed cell death protein 1 (PD1), anti-PD1 ligand 1 (PDL1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) therapies in advanced cancer, a considerable proportion of patients remain unresponsive to these treatments (known as innate resistance). In addition, one-third of patients relapse after initial response (known as adaptive resistance), which suggests that multiple non-redundant immunosuppressive mechanisms coexist within the tumour microenvironment. A major immunosuppressive mechanism is the adenosinergic pathway, which now represents an attractive new therapeutic target for cancer therapy. Activation of this pathway occurs within hypoxic tumours, where extracellular adenosine exerts local suppression through tumour-intrinsic and host-mediated mechanisms. Preclinical studies in mice with adenosine receptor antagonists and antibodies have reported favourable antitumour immune responses with some definition of the mechanism of action. Currently, agents targeting the adenosinergic pathway are undergoing first-in-human clinical trials as single agents and in combination with anti-PD1 or anti-PDL1 therapies. In this Review, we describe the complex interplay of adenosine and adenosine receptors in the development of primary tumours and metastases and discuss the merits of targeting one or more components that compose the adenosinergic pathway. We also review the early clinical data relating to therapeutic agents inhibiting the adenosinergic pathway.

    更新日期:2017-10-30
  • Preclinical mouse solid tumour models: status quo, challenges and perspectives
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-10-27
    Nicolas Gengenbacher, Mahak Singhal, Hellmut G. Augustin

    Preclinical mouse solid tumour models: status quo, challenges and perspectives Nature Reviews Cancer, Published online: 27 October 2017; doi:10.1038/nrc.2017.92 This Analysis examines preclinical mouse tumour studies published in eight scientific journals in 2016. It reviews current practices, identifies some important challenges and discusses ways in which the relevance, reproducibility and translatability of tumour models could be improved.

    更新日期:2017-10-30
  • Metabolism: More lactate, please
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-10-27
    Ulrike Harjes

    Metabolism: More lactate, please Nature Reviews Cancer, Published online: 27 October 2017; doi:10.1038/nrc.2017.101 The importance of 'Warburgian' metabolism in cancer is an increasingly disputed topic. By studying cancer metabolism in patients and mouse models, Faubert et al. now show that lactate is used as a respiratory fuel in non-small-cell lung cancer in vivo.

    更新日期:2017-10-30
  • Small-cell lung cancer: what we know, what we need to know and the path forward
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-10-27
    Adi F. Gazdar, Paul A. Bunn, John D. Minna

    Small-cell lung cancer (SCLC) is a deadly tumour accounting for approximately 15% of lung cancers and is pathologically, molecularly, biologically and clinically very different from other lung cancers. While the majority of tumours express a neuroendocrine programme (integrating neural and endocrine properties), an important subset of tumours have low or absent expression of this programme. The probable initiating molecular events are inactivation of TP53 and RB1, as well as frequent disruption of several signalling networks, including Notch signalling. SCLC, when diagnosed, is usually widely metastatic and initially responds to cytotoxic therapy but nearly always rapidly relapses with resistance to further therapies. There were no important therapeutic clinical advances for 30 years, leading SCLC to be designated a 'recalcitrant cancer'. Scientific studies are hampered by a lack of tissue availability. However, over the past 5 years, there has been a worldwide resurgence of studies on SCLC, including comprehensive molecular analyses, the development of relevant genetically engineered mouse models and the establishment of patient-derived xenografts. These studies have led to the discovery of new potential therapeutic vulnerabilities for SCLC and therefore to new clinical trials. Thus, while the past has been bleak, the future offers greater promise.

    更新日期:2017-10-30
  • Cancer models: Escaping those primitive origins
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-10-27
    Anna Dart

    Cancer models: Escaping those primitive origins Nature Reviews Cancer, Published online: 27 October 2017; doi:10.1038/nrc.2017.100 An embryonic avian model recapitulates the early stages of tumorigenesis and metastases seen in patients with neuroblastoma.

    更新日期:2017-10-30
  • Targeted therapies: Understanding tumour drug addiction
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-01
    Conor A. Bradley

    Targeted therapies: Understanding tumour drug addiction Nature Reviews Cancer, Published online: 25 October 2017; doi:10.1038/nrc.2017.98 Kong et al. report a mechanism that underlies tumour 'drug addiction' in melanoma cell lines and mouse models involving an ERK2-dependent phenotype switch, which might have clinical implications for the use of alternating treatment strategies with targeted therapies.

    更新日期:2017-10-30
  • Understanding and targeting resistance mechanisms in NSCLC
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-11-01
    Julia Rotow, Trever G. Bivona

    The expanding spectrum of both established and candidate oncogenic driver mutations identified in non-small-cell lung cancer (NSCLC), coupled with the increasing number of clinically available signal transduction pathway inhibitors targeting these driver mutations, offers a tremendous opportunity to enhance patient outcomes. Despite these molecular advances, advanced-stage NSCLC remains largely incurable due to therapeutic resistance. In this Review, we discuss alterations in the targeted oncogene ('on-target' resistance) and in other downstream and parallel pathways ('off-target' resistance) leading to resistance to targeted therapies in NSCLC, and we provide an overview of the current understanding of the bidirectional interactions with the tumour microenvironment that promote therapeutic resistance. We highlight common mechanistic themes underpinning resistance to targeted therapies that are shared by NSCLC subtypes, including those with oncogenic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS1 proto-oncogene receptor tyrosine kinase (ROS1), serine/threonine-protein kinase b-raf (BRAF) and other less established oncoproteins. Finally, we discuss how understanding these themes can inform therapeutic strategies, including combination therapy approaches, and overcome the challenge of tumour heterogeneity.

    更新日期:2017-10-30
  • Targeting immunosuppressive adenosine in cancer
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-10-23
    Dipti Vijayan, Arabella Young, Michele W.L. Teng, Mark J. Smyth

    Targeting immunosuppressive adenosine in cancer Nature Reviews Cancer, Published online: 23 October 2017; doi:10.1038/nrc.2017.86 The adenosinergic pathway is a major immunosuppressive mechanism in the tumour microenvironment. In this Review, Vijayan et al. discuss how targeting components involved in the generation and downstream signalling of extracellular adenosine represents an attractive novel cancer therapy.

    更新日期:2017-10-30
  • Engineering and physical sciences in oncology: challenges and opportunities
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Michael J. Mitchell, Rakesh K. Jain, Robert Langer

    The principles of engineering and physics have been applied to oncology for nearly 50 years. Engineers and physical scientists have made contributions to all aspects of cancer biology, from quantitative understanding of tumour growth and progression to improved detection and treatment of cancer. Many early efforts focused on experimental and computational modelling of drug distribution, cell cycle kinetics and tumour growth dynamics. In the past decade, we have witnessed exponential growth at the interface of engineering, physics and oncology that has been fuelled by advances in fields including materials science, microfabrication, nanomedicine, microfluidics, imaging, and catalysed by new programmes at the National Institutes of Health (NIH), including the National Institute of Biomedical Imaging and Bioengineering (NIBIB), Physical Sciences in Oncology, and the National Cancer Institute (NCI) Alliance for Nanotechnology. Here, we review the advances made at the interface of engineering and physical sciences and oncology in four important areas: the physical microenvironment of the tumour and technological advances in drug delivery; cellular and molecular imaging; and microfluidics and microfabrication. We discussthe research advances, opportunities and challenges for integrating engineering and physical sciences with oncology to develop new methods to study, detect and treat cancer, and we also describe the future outlook for these emerging areas.

    更新日期:2017-10-13
  • Non-small cell lung cancer: Where there's smoke...
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Ulrike Harjes

    Non-small cell lung cancer: Where there's smoke... Nature Reviews Cancer, Published online: 13 October 2017; doi:10.1038/nrc.2017.95 A recent study shows that smoking-induced epigenetic changes in lung epithelium occur even before malignant transformation, and sensitize the cells to allow a single key oncogenic event to initiate the growth of a tumour.

    更新日期:2017-10-13
  • Immunotherapy: When viruses attack
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Anna Dart

    Immunotherapy: When viruses attack Nature Reviews Cancer, Published online: 13 October 2017; doi:10.1038/nrc.2017.97 Two studies have shown the potential of oncolytic viruses to reverse immunosuppression in the tumour microenvironment.

    更新日期:2017-10-13
  • Genome-wide association studies of cancer: current insights and future perspectives
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Amit Sud, Ben Kinnersley, Richard S. Houlston

    Genome-wide association studies (GWAS) provide an agnostic approach for investigating the genetic basis of complex diseases. In oncology, GWAS of nearly all common malignancies have been performed, and over 450 genetic variants associated with increased risks have been identified. As well as revealing novel pathways important in carcinogenesis, these studies have shown that common genetic variation contributes substantially to the heritable risk of many common cancers. The clinical application of GWAS is starting to provide opportunities for drug discovery and repositioning as well as for cancer prevention. However, deciphering the functional and biological basis of associations is challenging and is in part a barrier to fully unlocking the potential of GWAS.

    更新日期:2017-10-13
  • Engineering and physical sciences in oncology: challenges and opportunities
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Michael J. Mitchell, Rakesh K. Jain, Robert Langer

    The principles of engineering and physics have been applied to oncology for nearly 50 years. Engineers and physical scientists have made contributions to all aspects of cancer biology, from quantitative understanding of tumour growth and progression to improved detection and treatment of cancer. Many early efforts focused on experimental and computational modelling of drug distribution, cell cycle kinetics and tumour growth dynamics. In the past decade, we have witnessed exponential growth at the interface of engineering, physics and oncology that has been fuelled by advances in fields including materials science, microfabrication, nanomedicine, microfluidics, imaging, and catalysed by new programmes at the National Institutes of Health (NIH), including the National Institute of Biomedical Imaging and Bioengineering (NIBIB), Physical Sciences in Oncology, and the National Cancer Institute (NCI) Alliance for Nanotechnology. Here, we review the advances made at the interface of engineering and physical sciences and oncology in four important areas: the physical microenvironment of the tumour and technological advances in drug delivery; cellular and molecular imaging; and microfluidics and microfabrication. We discussthe research advances, opportunities and challenges for integrating engineering and physical sciences with oncology to develop new methods to study, detect and treat cancer, and we also describe the future outlook for these emerging areas.

    更新日期:2017-10-13
  • Non-small cell lung cancer: Where there's smoke...
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Ulrike Harjes

    Non-small cell lung cancer: Where there's smoke... Nature Reviews Cancer, Published online: 13 October 2017; doi:10.1038/nrc.2017.95 A recent study shows that smoking-induced epigenetic changes in lung epithelium occur even before malignant transformation, and sensitize the cells to allow a single key oncogenic event to initiate the growth of a tumour.

    更新日期:2017-10-13
  • Immunotherapy: When viruses attack
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Anna Dart

    Immunotherapy: When viruses attack Nature Reviews Cancer, Published online: 13 October 2017; doi:10.1038/nrc.2017.97 Two studies have shown the potential of oncolytic viruses to reverse immunosuppression in the tumour microenvironment.

    更新日期:2017-10-13
  • Genome-wide association studies of cancer: current insights and future perspectives
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Amit Sud, Ben Kinnersley, Richard S. Houlston

    Genome-wide association studies of cancer: current insights and future perspectives Nature Reviews Cancer, Published online: 13 October 2017; doi:10.1038/nrc.2017.82 Genome-wide association studies (GWAS) uncover the impact of genetic variation on the risk of many common cancers. This Review discusses current insights and how understanding the biological basis of these associations is required to maximise the clinical benefit of GWAS.

    更新日期:2017-10-13
  • Immunotherapy: CD8+ T cells — burn fat, get fit
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Conor A. Bradley

    Immunotherapy: CD8+ T cells — burn fat, get fit Nature Reviews Cancer, Published online: 6 October 2017; doi:10.1038/nrc.2017.94 Zhang et al. report that CD8+ tumour-infiltrating T lymphocytes exposed to a hypoglycaemic and hypoxic tumour microenvironment enhance PPARα signalling and fatty acid catabolism to partially preserve effector functions and increase the efficacy of immunotherapy in melanoma mouse models.

    更新日期:2017-10-11
  • New perspectives for targeting RAF kinase in human cancer
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Zoi Karoulia, Evripidis Gavathiotis, Poulikos I. Poulikakos

    The discovery that a subset of human tumours is dependent on mutationally deregulated BRAF kinase intensified the development of RAF inhibitors to be used as potential therapeutics. The US Food and Drug Administration (FDA)-approved second-generation RAF inhibitors vemurafenib and dabrafenib have elicited remarkable responses and improved survival of patients with BRAF-V600E/K melanoma, but their effectiveness is limited by resistance. Beyond melanoma, current clinical RAF inhibitors show modest efficacy when used for colorectal and thyroid BRAF-V600E tumours or for tumours harbouring BRAF alterations other than the V600 mutation. Accumulated experimental and clinical evidence indicates that the complex biochemical mechanisms of RAF kinase signalling account both for the effectiveness of RAF inhibitors and for the various mechanisms of tumour resistance to them. Recently, a number of next-generation RAF inhibitors, with diverse structural and biochemical properties, have entered preclinical and clinical development. In this Review, we discuss the current understanding of RAF kinase regulation, mechanisms of inhibitor action and related clinical resistance to these drugs. The recent elucidation of critical structural and biochemical aspects of RAF inhibitor action, combined with the availability of a number of structurally diverse RAF inhibitors currently in preclinical and clinical development, will enable the design of more effective RAF inhibitors and RAF-inhibitor-based therapeutic strategies, tailored to different clinical contexts.

    更新日期:2017-10-11
  • Immunotherapy: CD8+ T cells — burn fat, get fit
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Conor A. Bradley

    Immunotherapy: CD8+ T cells — burn fat, get fit Nature Reviews Cancer, Published online: 6 October 2017; doi:10.1038/nrc.2017.94 Zhang et al. report that CD8+ tumour-infiltrating T lymphocytes exposed to a hypoglycaemic and hypoxic tumour microenvironment enhance PPARα signalling and fatty acid catabolism to partially preserve effector functions and increase the efficacy of immunotherapy in melanoma mouse models.

    更新日期:2017-10-11
  • New perspectives for targeting RAF kinase in human cancer
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Zoi Karoulia, Evripidis Gavathiotis, Poulikos I. Poulikakos

    The discovery that a subset of human tumours is dependent on mutationally deregulated BRAF kinase intensified the development of RAF inhibitors to be used as potential therapeutics. The US Food and Drug Administration (FDA)-approved second-generation RAF inhibitors vemurafenib and dabrafenib have elicited remarkable responses and improved survival of patients with BRAF-V600E/K melanoma, but their effectiveness is limited by resistance. Beyond melanoma, current clinical RAF inhibitors show modest efficacy when used for colorectal and thyroid BRAF-V600E tumours or for tumours harbouring BRAF alterations other than the V600 mutation. Accumulated experimental and clinical evidence indicates that the complex biochemical mechanisms of RAF kinase signalling account both for the effectiveness of RAF inhibitors and for the various mechanisms of tumour resistance to them. Recently, a number of next-generation RAF inhibitors, with diverse structural and biochemical properties, have entered preclinical and clinical development. In this Review, we discuss the current understanding of RAF kinase regulation, mechanisms of inhibitor action and related clinical resistance to these drugs. The recent elucidation of critical structural and biochemical aspects of RAF inhibitor action, combined with the availability of a number of structurally diverse RAF inhibitors currently in preclinical and clinical development, will enable the design of more effective RAF inhibitors and RAF-inhibitor-based therapeutic strategies, tailored to different clinical contexts.

    更新日期:2017-10-11
  • Exercise-dependent regulation of the tumour microenvironment
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Graeme J. Koelwyn, Daniela F. Quail, Xiang Zhang, Richard M. White, Lee W. Jones

    Exercise-dependent regulation of the tumour microenvironment Nature Reviews Cancer, Published online: 25 September 2017; doi:10.1038/nrc.2017.78 Emerging data indicate that exercise modulates cancer biology and disease outcomes; however, the molecular mechanisms are poorly established. In this Opinion article, the authors speculate on how exercise might reprogramme the tumour microenvironment to influence cancer hallmarks.

    更新日期:2017-09-25
  • Cell death: A better way to die
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Anna Dart

    Cell death: A better way to die Nature Reviews Cancer, Published online: 25 September 2017; doi:10.1038/nrc.2017.90

    更新日期:2017-09-25
  • Glioblastoma: Stem cells — masters of their fates
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Conor A. Bradley

    Glioblastoma: Stem cells — masters of their fates Nature Reviews Cancer, Published online: 25 September 2017; doi:10.1038/nrc.2017.88 Using DNA barcoding, Lan et al. investigated the clonal evolution and dynamics of glioblastoma cells, and propose a model whereby proliferative heterogeneity is derived from stochastic fate decisions made by a homogeneous population of glioblastoma stem cells and their progeny.

    更新日期:2017-09-25
  • The benefits of speaking a common language
    Nat. Rev. Cancer (IF 37.147) Pub Date : 

    The benefits of speaking a common language Nature Reviews Cancer, Published online: 25 September 2017; doi:10.1038/nrc.2017.91 This issue marks the publication of a Consensus Statement that proposes a classification system for the evolutionary and ecological features of cancers.

    更新日期:2017-09-25
  • Leukaemia: The real deal
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Ulrike Harjes

    Leukaemia: The real deal Nature Reviews Cancer, Published online: 25 September 2017; doi:10.1038/nrc.2017.89

    更新日期:2017-09-25
  • Exercise-dependent regulation of the tumour microenvironment
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Graeme J. Koelwyn, Daniela F. Quail, Xiang Zhang, Richard M. White, Lee W. Jones

    Exercise-dependent regulation of the tumour microenvironment Nature Reviews Cancer, Published online: 25 September 2017; doi:10.1038/nrc.2017.78 Emerging data indicate that exercise modulates cancer biology and disease outcomes; however, the molecular mechanisms are poorly established. In this Opinion article, the authors speculate on how exercise might reprogramme the tumour microenvironment to influence cancer hallmarks.

    更新日期:2017-09-25
  • Cell death: A better way to die
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Anna Dart

    Cell death: A better way to die Nature Reviews Cancer, Published online: 25 September 2017; doi:10.1038/nrc.2017.90

    更新日期:2017-09-25
  • Glioblastoma: Stem cells — masters of their fates
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Conor A. Bradley

    Glioblastoma: Stem cells — masters of their fates Nature Reviews Cancer, Published online: 25 September 2017; doi:10.1038/nrc.2017.88 Using DNA barcoding, Lan et al. investigated the clonal evolution and dynamics of glioblastoma cells, and propose a model whereby proliferative heterogeneity is derived from stochastic fate decisions made by a homogeneous population of glioblastoma stem cells and their progeny.

    更新日期:2017-09-25
  • The benefits of speaking a common language
    Nat. Rev. Cancer (IF 37.147) Pub Date : 

    The benefits of speaking a common language Nature Reviews Cancer, Published online: 25 September 2017; doi:10.1038/nrc.2017.91 This issue marks the publication of a Consensus Statement that proposes a classification system for the evolutionary and ecological features of cancers.

    更新日期:2017-09-25
  • Leukaemia: The real deal
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Ulrike Harjes

    Leukaemia: The real deal Nature Reviews Cancer, Published online: 25 September 2017; doi:10.1038/nrc.2017.89

    更新日期:2017-09-25
  • Classifying the evolutionary and ecological features of neoplasms
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Carlo C. Maley, Athena Aktipis, Trevor A. Graham, Andrea Sottoriva, Amy M. Boddy, Michalina Janiszewska, Ariosto S. Silva, Marco Gerlinger, Yinyin Yuan, Kenneth J. Pienta, Karen S. Anderson, Robert Gatenby, Charles Swanton, David Posada, Chung-I Wu, Joshua D. Schiffman, E. Shelley Hwang, Kornelia Polyak, Alexander R. A. Anderson, Joel S. Brown, Mel Greaves, Darryl Shibata

    Classifying the evolutionary and ecological features of neoplasms Nature Reviews Cancer, Published online: 15 September 2017; doi:10.1038/nrc.2017.69 Based on a consensus conference of experts in the evolution and ecology of cancer, this article proposes a framework for classifying tumours that includes four evolutionary and ecological processes: neoplastic cell diversity and changes over time in that diversity, hazards to cell survival and available resources.

    更新日期:2017-09-15
  • Tumour acidosis: from the passenger to the driver's seat
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Cyril Corbet, Olivier Feron

    The high metabolic demand of cancer cells leads to an accumulation of H+ ions in the tumour microenvironment. The disorganized tumour vasculature prevents an efficient wash-out of H+ ions released into the extracellular medium but also favours the development of tumour hypoxic regions associated with a shift towards glycolytic metabolism. Under hypoxia, the final balance of glycolysis, including breakdown of generated ATP, is the production of lactate and a stoichiometric amount of H+ ions. Another major source of H+ ions results from hydration of CO2 produced in the more oxidative tumour areas. All of these events occur at high rates in tumours to fulfil bioenergetic and biosynthetic needs. This Review summarizes the current understanding of how H+-generating metabolic processes segregate within tumours according to the distance from blood vessels and inversely how ambient acidosis influences tumour metabolism, reducing glycolysis while promoting mitochondrial activity. The Review also presents novel insights supporting the participation of acidosis in cancer progression via stimulation of autophagy and immunosuppression. Finally, recent advances in the different therapeutic modalities aiming to either block pH-regulatory systems or exploit acidosis will be discussed.

    更新日期:2017-09-15
  • Interrogating open issues in cancer medicine with patient-derived xenografts
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Annette T. Byrne, Denis G. Alférez, Frédéric Amant, Daniela Annibali, Joaquín Arribas, Andrew V. Biankin, Alejandra Bruna, Eva Budinská, Carlos Caldas, David K. Chang, Robert B. Clarke, Hans Clevers, George Coukos, Virginie Dangles-Marie, S. Gail Eckhardt, Eva Gonzalez-Suarez, Els Hermans, Manuel Hidalgo, Monika A. Jarzabek, Steven de Jong, Jos Jonkers, Kristel Kemper, Luisa Lanfrancone, Gunhild Mari Mælandsmo, Elisabetta Marangoni, Jean-Christophe Marine, Enzo Medico, Jens Henrik Norum, Héctor G. Palmer, Daniel S. Peeper, Pier Giuseppe Pelicci, Alejandro Piris-Gimenez, Sergio Roman-Roman, Oscar M. Rueda, Joan Seoane, Violeta Serra, Laura Soucek, Dominique Vanhecke, Alberto Villanueva, Emilie Vinolo, Andrea Bertotti, Livio Trusolino

    Interrogating open issues in cancer medicine with patient-derived xenografts Nature Reviews Cancer, Published online: 15 September 2017; doi:10.1038/nrc.2017.85

    更新日期:2017-09-15
  • Classifying the evolutionary and ecological features of neoplasms
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-09-15
    Carlo C. Maley, Athena Aktipis, Trevor A. Graham, Andrea Sottoriva, Amy M. Boddy, Michalina Janiszewska, Ariosto S. Silva, Marco Gerlinger, Yinyin Yuan, Kenneth J. Pienta, Karen S. Anderson, Robert Gatenby, Charles Swanton, David Posada, Chung-I Wu, Joshua D. Schiffman, E. Shelley Hwang, Kornelia Polyak, Alexander R. A. Anderson, Joel S. Brown, Mel Greaves, Darryl Shibata

    Classifying the evolutionary and ecological features of neoplasms Nature Reviews Cancer, Published online: 15 September 2017; doi:10.1038/nrc.2017.69 Based on a consensus conference of experts in the evolution and ecology of cancer, this article proposes a framework for classifying tumours that includes four evolutionary and ecological processes: neoplastic cell diversity and changes over time in that diversity, hazards to cell survival and available resources.

    更新日期:2017-09-15
  • Tumour acidosis: from the passenger to the driver's seat
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-09-15
    Cyril Corbet, Olivier Feron

    The high metabolic demand of cancer cells leads to an accumulation of H+ ions in the tumour microenvironment. The disorganized tumour vasculature prevents an efficient wash-out of H+ ions released into the extracellular medium but also favours the development of tumour hypoxic regions associated with a shift towards glycolytic metabolism. Under hypoxia, the final balance of glycolysis, including breakdown of generated ATP, is the production of lactate and a stoichiometric amount of H+ ions. Another major source of H+ ions results from hydration of CO2 produced in the more oxidative tumour areas. All of these events occur at high rates in tumours to fulfil bioenergetic and biosynthetic needs. This Review summarizes the current understanding of how H+-generating metabolic processes segregate within tumours according to the distance from blood vessels and inversely how ambient acidosis influences tumour metabolism, reducing glycolysis while promoting mitochondrial activity. The Review also presents novel insights supporting the participation of acidosis in cancer progression via stimulation of autophagy and immunosuppression. Finally, recent advances in the different therapeutic modalities aiming to either block pH-regulatory systems or exploit acidosis will be discussed.

    更新日期:2017-09-15
  • Interrogating open issues in cancer medicine with patient-derived xenografts
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Annette T. Byrne, Denis G. Alférez, Frédéric Amant, Daniela Annibali, Joaquín Arribas, Andrew V. Biankin, Alejandra Bruna, Eva Budinská, Carlos Caldas, David K. Chang, Robert B. Clarke, Hans Clevers, George Coukos, Virginie Dangles-Marie, S. Gail Eckhardt, Eva Gonzalez-Suarez, Els Hermans, Manuel Hidalgo, Monika A. Jarzabek, Steven de Jong, Jos Jonkers, Kristel Kemper, Luisa Lanfrancone, Gunhild Mari Mælandsmo, Elisabetta Marangoni, Jean-Christophe Marine, Enzo Medico, Jens Henrik Norum, Héctor G. Palmer, Daniel S. Peeper, Pier Giuseppe Pelicci, Alejandro Piris-Gimenez, Sergio Roman-Roman, Oscar M. Rueda, Joan Seoane, Violeta Serra, Laura Soucek, Dominique Vanhecke, Alberto Villanueva, Emilie Vinolo, Andrea Bertotti, Livio Trusolino

    Interrogating open issues in cancer medicine with patient-derived xenografts Nature Reviews Cancer, Published online: 15 September 2017; doi:10.1038/nrc.2017.85

    更新日期:2017-09-15
  • Leukaemia: Beyond the C
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-09-08
    Ulrike Harjes

    Leukaemia: Beyond the C Nature Reviews Cancer, Published online: 8 September 2017; doi:10.1038/nrc.2017.81 Vitamin C supplementation has shown limited benefits in patients with solid tumours. Two studies report that vitamin C supplementation can reduce Tet-dependent leukaemia progression in mice, supporting the concept of high-dose vitamin C supplementation in certain patients with haematological malignancies.

    更新日期:2017-09-15
  • Prostate cancer: BET inhibitors — SPOP right there!
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-09-08
    Conor A. Bradley

    Prostate cancer: BET inhibitors — SPOP right there! Nature Reviews Cancer, Published online: 8 September 2017; doi:10.1038/nrc.2017.80 Although speckle-type POZ protein (SPOP) is the most frequently mutated gene in primary prostate cancer, its therapeutic implications are incompletely understood. Now, three studies describe mechanisms of resistance to bromodomain and extraterminal (BET) protein inhibitors in SPOP-mutated prostate cancer.

    更新日期:2017-09-15
  • Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence
    Nat. Rev. Cancer (IF 37.147) Pub Date : 2017-09-01
    Veronique Giroux, Anil K. Rustgi

    Metaplasia is the replacement of one differentiated somatic cell type with another differentiated somatic cell type in the same tissue. Typically, metaplasia is triggered by environmental stimuli, which may act in concert with the deleterious effects of microorganisms and inflammation. The cell of origin for intestinal metaplasia in the oesophagus and stomach and for pancreatic acinar–ductal metaplasia has been posited through genetic mouse models and lineage tracing but has not been identified in other types of metaplasia, such as squamous metaplasia. A hallmark of metaplasia is a change in cellular identity, and this process can be regulated by transcription factors that initiate and/or maintain cellular identity, perhaps in concert with epigenetic reprogramming. Universally, metaplasia is a precursor to low-grade dysplasia, which can culminate in high-grade dysplasia and carcinoma. Improved clinical screening for and surveillance of metaplasia might lead to better prevention or early detection of dysplasia and cancer.

    更新日期:2017-09-15
  • Targeting neoantigens to augment antitumour immunity
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Mark Yarchoan, Burles A. Johnson III, Eric R. Lutz, Daniel A. Laheru, Elizabeth M. Jaffee

    Targeting neoantigens to augment antitumour immunity Nature Reviews Cancer, Published online: 24 August 2017; doi:10.1038/nrc.2017.74

    更新日期:2017-09-15
  • Metastasis: Throwing oil into the flames
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Ulrike Harjes

    Metastasis: Throwing oil into the flames Nature Reviews Cancer, Published online: 24 August 2017; doi:10.1038/nrc.2017.76 Both obesity and systemic inflammation promote cancer progression, although how obesity-associated inflammation affects cancer metastasis is poorly understood. Quail et al. now show that obesity induces cytokines that stimulate lung neutrophilia in mice, thereby promoting breast cancer metastasis.

    更新日期:2017-09-15
  • Leukaemia: Beyond the C
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Ulrike Harjes

    Leukaemia: Beyond the C Nature Reviews Cancer, Published online: 8 September 2017; doi:10.1038/nrc.2017.81 Vitamin C supplementation has shown limited benefits in patients with solid tumours. Two studies report that vitamin C supplementation can reduce Tet-dependent leukaemia progression in mice, supporting the concept of high-dose vitamin C supplementation in certain patients with haematological malignancies.

    更新日期:2017-09-14
  • Prostate cancer: BET inhibitors — SPOP right there!
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Conor A. Bradley

    Prostate cancer: BET inhibitors — SPOP right there! Nature Reviews Cancer, Published online: 8 September 2017; doi:10.1038/nrc.2017.80 Although speckle-type POZ protein (SPOP) is the most frequently mutated gene in primary prostate cancer, its therapeutic implications are incompletely understood. Now, three studies describe mechanisms of resistance to bromodomain and extraterminal (BET) protein inhibitors in SPOP-mutated prostate cancer.

    更新日期:2017-09-14
  • Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence
    Nat. Rev. Cancer (IF 37.147) Pub Date : 
    Veronique Giroux, Anil K. Rustgi

    Metaplasia is the replacement of one differentiated somatic cell type with another differentiated somatic cell type in the same tissue. Typically, metaplasia is triggered by environmental stimuli, which may act in concert with the deleterious effects of microorganisms and inflammation. The cell of origin for intestinal metaplasia in the oesophagus and stomach and for pancreatic acinar–ductal metaplasia has been posited through genetic mouse models and lineage tracing but has not been identified in other types of metaplasia, such as squamous metaplasia. A hallmark of metaplasia is a change in cellular identity, and this process can be regulated by transcription factors that initiate and/or maintain cellular identity, perhaps in concert with epigenetic reprogramming. Universally, metaplasia is a precursor to low-grade dysplasia, which can culminate in high-grade dysplasia and carcinoma. Improved clinical screening for and surveillance of metaplasia might lead to better prevention or early detection of dysplasia and cancer.

    更新日期:2017-09-14
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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