Lucy Bird
No abstract text is available yet for this article.
December 2015: Nature Reviews. Drug Discovery
Nicholas E Navin
Single-cell sequencing methods are revolutionizing cancer research and medicine by providing powerful tools to investigate intratumor heterogeneity and rare subpopulations.
July 15, 2015: Science Translational Medicine
David L Porter, Wei-Ting Hwang, Noelle V Frey, Simon F Lacey, Pamela A Shaw, Alison W Loren, Adam Bagg, Katherine T Marcucci, Angela Shen, Vanessa Gonzalez, David Ambrose, Stephan A Grupp, Anne Chew, Zhaohui Zheng, Michael C Milone, Bruce L Levine, Jan J Melenhorst, Carl H June
Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a poor prognosis. Chimeric antigen receptor (CAR)-modified T cells targeting CD19 have the potential to improve on the low complete response rates with conventional therapies by inducing sustained remissions in patients with refractory B cell malignancies. We previously reported preliminary results on three patients with refractory CLL. We report the mature results from our initial trial using CAR-modified T cells to treat 14 patients with relapsed and refractory CLL...
September 2, 2015: Science Translational Medicine
Steven M Larson, Jorge A Carrasquillo, Nai-Kong V Cheung, Oliver W Press
The eradication of cancer remains a vexing problem despite recent advances in our understanding of the molecular basis of neoplasia. One therapeutic approach that has demonstrated potential involves the selective targeting of radionuclides to cancer-associated cell surface antigens using monoclonal antibodies. Such radioimmunotherapy (RIT) permits the delivery of a high dose of therapeutic radiation to cancer cells, while minimizing the exposure of normal cells. Although this approach has been investigated for several decades, the cumulative advances in cancer biology, antibody engineering and radiochemistry in the past decade have markedly enhanced the ability of RIT to produce durable remissions of multiple cancer types...
June 2015: Nature Reviews. Cancer
Fredrik Mertens, Bertil Johansson, Thoas Fioretos, Felix Mitelman
Structural chromosome rearrangements may result in the exchange of coding or regulatory DNA sequences between genes. Many such gene fusions are strong driver mutations in neoplasia and have provided fundamental insights into the disease mechanisms that are involved in tumorigenesis. The close association between the type of gene fusion and the tumour phenotype makes gene fusions ideal for diagnostic purposes, enabling the subclassification of otherwise seemingly identical disease entities. In addition, many gene fusions add important information for risk stratification, and increasing numbers of chimeric proteins encoded by the gene fusions serve as specific targets for treatment, resulting in dramatically improved patient outcomes...
June 2015: Nature Reviews. Cancer
Alexandra Flemming
No abstract text is available yet for this article.
January 2015: Nature Reviews. Drug Discovery
Silvana Konermann, Mark D Brigham, Alexandro E Trevino, Julia Joung, Omar O Abudayyeh, Clea Barcena, Patrick D Hsu, Naomi Habib, Jonathan S Gootenberg, Hiroshi Nishimasu, Osamu Nureki, Feng Zhang
Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. Here we describe structure-guided engineering of a CRISPR-Cas9 complex to mediate efficient transcriptional activation at endogenous genomic loci. We used these engineered Cas9 activation complexes to investigate single-guide RNA (sgRNA) targeting rules for effective transcriptional activation, to demonstrate multiplexed activation of ten genes simultaneously, and to upregulate long intergenic non-coding RNA (lincRNA) transcripts...
January 29, 2015: Nature
Carlos López-Otín, Maria A Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer
Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution...
June 6, 2013: Cell
Robert Brown, Edward Curry, Luca Magnani, Charlotte S Wilhelm-Benartzi, Jane Borley
Epigenetic events, which are somatically inherited through cell division, are potential drivers of acquired drug resistance in cancer. The high rate of epigenetic change in tumours generates diversity in gene expression patterns that can rapidly evolve through drug selection during treatment, leading to the development of acquired resistance. This will potentially confound stratified chemotherapy decisions that are solely based on mutation biomarkers. Poised epigenetic states in tumour cells may drive multistep epigenetic fixation of gene expression during the acquisition of drug resistance, which has implications for clinical strategies to prevent the emergence of drug resistance...
November 2014: Nature Reviews. Cancer
B Harpreet Singh, James L Gulley
Cancer immunotherapy was deemed the medical breakthrough of 2013, in part because it can induce a rapid, durable, self-propagating and adaptable immune response. Specifically in prostate cancer, immunotherapy has emerged as a viable and attractive treatment strategy. To date, therapeutic cancer vaccines and immune checkpoint inhibitors are the two classes of immunotherapy that have demonstrated improvements in overall survival in patients with advanced tumors. The 2010 Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab...
September 2014: Therapeutic Advances in Vaccines
María Soledad Sosa, Paloma Bragado, Julio A Aguirre-Ghiso
Metastases arise from residual disseminated tumour cells (DTCs). This can happen years after primary tumour treatment because residual tumour cells can enter dormancy and evade therapies. As the biology of minimal residual disease seems to diverge from that of proliferative lesions, understanding the underpinnings of this new cancer biology is key to prevent metastasis. Analysis of approximately 7 years of literature reveals a growing focus on tumour and normal stem cell quiescence, extracellular and stromal microenvironments, autophagy and epigenetics as mechanisms that dictate tumour cell dormancy...
September 2014: Nature Reviews. Cancer
Louise van der Weyden, Marco Ranzani, David J Adams
A new study describes a tool, Lentihop, for somatic insertional mutagenesis in human cells and uses this system in combination with cancer genome data to define new genes and pathways involved in sarcoma development. Gene discovery in this way suggests that we are far from a complete catalog of cancer drivers.
September 2014: Nature Genetics
Katrina J Falkenberg, Ricky W Johnstone
Epigenetic aberrations, which are recognized as key drivers of several human diseases, are often caused by genetic defects that result in functional deregulation of epigenetic proteins, their altered expression and/or their atypical recruitment to certain gene promoters. Importantly, epigenetic changes are reversible, and epigenetic enzymes and regulatory proteins can be targeted using small molecules. This Review discusses the role of altered expression and/or function of one class of epigenetic regulators--histone deacetylases (HDACs)--and their role in cancer, neurological diseases and immune disorders...
September 2014: Nature Reviews. Drug Discovery
M Teresa Villanueva
No abstract text is available yet for this article.
September 2014: Nature Reviews. Clinical Oncology
Diwakar R Pattabiraman, Robert A Weinberg
Since their identification in 1994, cancer stem cells (CSCs) have been objects of intensive study. Their properties and mechanisms of formation have become a major focus of current cancer research, in part because of their enhanced ability to initiate and drive tumour growth and their intrinsic resistance to conventional therapeutics. The discovery that activation of the epithelial-to-mesenchymal transition (EMT) programme in carcinoma cells can give rise to cells with stem-like properties has provided one possible mechanism explaining how CSCs arise and presents a possible avenue for their therapeutic manipulation...
July 2014: Nature Reviews. Drug Discovery
Nicolas André, Manon Carré, Eddy Pasquier
Since its inception in 2000, metronomic chemotherapy has undergone major advances as an antiangiogenic therapy. The discovery of the pro-immune properties of chemotherapy and its direct effects on cancer cells has established the intrinsic multitargeted nature of this therapeutic approach. The past 10 years have seen a marked rise in clinical trials of metronomic chemotherapy, and it is increasingly combined in the clinic with conventional treatments, such as maximum-tolerated dose chemotherapy and radiotherapy, as well as with novel therapeutic strategies, such as drug repositioning, targeted agents and immunotherapy...
July 2014: Nature Reviews. Clinical Oncology
Marlies S Reimers, Charla C Engels, Peter J K Kuppen, Cornelis J H van de Velde, Gerrit J Liefers
Cancer is a leading cause of death worldwide. Great efforts are dedicated to the development of prognostic and predictive biomarkers to improve diagnosis and achieve optimal treatment selection, thereby, introducing precision medicine in the multimodality treatment of cancer. Genomic aberrations are the basis of tumour development, representing excellent candidates for the development of promising clinical biomarkers. Over the past decade, single-gene mutations and genomic profiling have been increasingly used in multidisciplinary consultations for risk-assessment and treatment planning for patients with cancer...
October 2014: Nature Reviews. Clinical Oncology
D Ross Camidge, William Pao, Lecia V Sequist
The use of advanced molecular profiling to direct the use of targeted therapy, such as tyrosine kinase inhibitors (TKIs) for patients with advanced-stage non-small-cell lung cancer (NSCLC), has revolutionized the treatment of this disease. However, acquired resistance, defined as progression after initial benefit, to targeted therapies inevitably occurs. This Review explores breakthroughs in the understanding and treatment of acquired resistance in NSCLC, focusing on EGFR mutant and ALK rearrangement-positive disease, which may be relevant across multiple different solid malignancies with oncogene-addicted subtypes...
August 2014: Nature Reviews. Clinical Oncology
Ignacio Melero, Gustav Gaudernack, Winald Gerritsen, Christoph Huber, Giorgio Parmiani, Suzy Scholl, Nicholas Thatcher, John Wagstaff, Christoph Zielinski, Ian Faulkner, Håkan Mellstedt
The therapeutic potential of host-specific and tumour-specific immune responses is well recognized and, after many years, active immunotherapies directed at inducing or augmenting these responses are entering clinical practice. Antitumour immunization is a complex, multi-component task, and the optimal combinations of antigens, adjuvants, delivery vehicles and routes of administration are not yet identified. Active immunotherapy must also address the immunosuppressive and tolerogenic mechanisms deployed by tumours...
September 2014: Nature Reviews. Clinical Oncology
Brian D Lichty, Caroline J Breitbach, David F Stojdl, John C Bell
Recent clinical data have emphatically shown the capacity of our immune systems to eradicate even advanced cancers. Although oncolytic viruses (OVs) were originally designed to function as tumour-lysing therapeutics, they have now been clinically shown to initiate systemic antitumour immune responses. Cell signalling pathways that are activated and promote the growth of tumour cells also favour the growth and replication of viruses within the cancer. The ability to engineer OVs that express immune-stimulating 'cargo', the induction of immunogenic tumour cell death by OVs and the selective targeting of OVs to tumour beds suggests that they are the ideal reagents to enhance antitumour immune responses...
August 2014: Nature Reviews. Cancer
2014-07-15 15:44:37
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