Nature Reviews Drug Discovery contents December 2013 Volume 12 Number 12 pp 887-963

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TABLE OF CONTENTS
December 2013 Volume 12 Number 12		Advertisement
Impact Factor 33.078 *	In this issue Comment News and Analysis Research Highlights Perspectives Reviews Correspondence Also this month  Featured article: Modulation of oxidative stress as an anticancer strategy Chiara Gorrini, Isaac S. Harris & Tak W. Mak	Improving the safety of cell therapy products by suicide gene transfer Topic Editors: Eric Robinet, Christophe Ferrand, and Marina Deschamps ¦ Deadline: 01 Sep 2014 This Research Topic from Frontiers in Pharmacology aims at presenting the suicide gene approach as a safety system for cell therapy products. This Topic will not be restricted to T cells, for which a large set of data have been published, and will also address other type of cell therapy products.  Find out how to contribute to this RT
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In this issue p887 | doi:10.1038/nrd4192 Full Text
Comment: Drugging cancer genomes Paul Workman & Bissan Al-Lazikani p889 | doi:10.1038/nrd4184 A recent landmark analysis compared genome-wide mutations and associated 'omics' features for 3,281 tumours across 12 human cancer types. There is a clear need for objective target assessment and prioritization by the drug discovery community to make the best use of such vast amounts of data. Full Text | PDF | Supplementary information
NEWS AND ANALYSIS		Top
Learning from the 2012-2013 class of breakthrough therapies Asher Mullard p891 | doi:10.1038/nrd4196 The expedited US regulatory pathway for 'breakthrough therapies' has already yielded its first two approvals and more than 26 designations, for 30 candidates in 22 indications. PDF
The GHIT fund shows its cards David Holmes p894 | doi:10.1038/nrd4197 Japan's biggest pharmaceutical companies, the Bill and Melinda Gates Foundation, and the Japanese government have awarded their first round of global health research grants. PDF
NEWS IN BRIEF Time to rethink dose-finding study design p895 | doi:10.1038/nrd4193 PDF
With great speed comes great need for post-marketing oversight? p895 | doi:10.1038/nrd4194 PDF
VC and non-profit unite to launch new companies p895 | doi:10.1038/nrd4195 PDF
BIOBUSINESS BRIEFS Market watch: Defining and quantifying the use of personalized medicines Sean X. Hu, Murray L. Aitken, Arnold M. Epstein, Mark R. Trusheim & Ernst R. Berndt p896 | doi:10.1038/nrd4177 PDF
BIOBUSINESS BRIEFS Trial watch: Phase II boost for glutamate-targeted antidepressants Monica Hoyos Flight p897 | doi:10.1038/nrd4178 PDF
PATENT WATCH NIH denies march-in rights on Norvir patent Charlotte Harrison p898 | doi:10.1038/nrd4198 PDF
Recent patents related to histone demethylases Charlotte Harrison p899 | doi:10.1038/nrd4199 PDF
AN AUDIENCE WITH Charles Hugh-Jones p900 | doi:10.1038/nrd4190 Charles Hugh-Jones, Chief Medical Officer in North America at Sanofi, discusses Project Data Sphere, a new collaborative platform for sharing cancer clinical trial data. PDF
FROM THE ANALYST'S COUCH Does size matter in R&D productivity? If not, what does? Michael Ringel, Peter Tollman, Greg Hersch & Ulrik Schulze p901 | doi:10.1038/nrd4164 This analysis of factors that affect the likelihood of success in drug research and development (R&D) indicates that scientific acumen and good judgment — particularly with regard to the early termination of less viable drug candidates — are crucial. PDF
RESEARCH HIGHLIGHTS Top Target identification: Blocking vasopressin receptors reduces jet lag p903 | doi:10.1038/nrd4180 PDF Neurodegenerative disease: Tau immunotherapy targets transcellular propagation p904 | doi:10.1038/nrd4179 PDF Bone disorders: Targeting NOX4 knocks down osteoporosis p904 | doi:10.1038/nrd4182 PDF Autoimmune disease: Parkinson's drug promotes myelin repair p905 | doi:10.1038/nrd4181 PDF Neurological disorders: Chloride extrusion alleviates neuropathic pain p906 | doi:10.1038/nrd4183 PDF IN BRIEF Neurodegenerative disease: A PERK for the therapy of prion disease | Target validation: Tinkering with heart disease | Neurodegenerative disease: Patient stem cells give clues to ALS | Computational biology: Structural insights into allosteric GPCR drugs PDF Drug Discovery JOBS of the week Postdoctoral Researcher in Biomaterials and Drug Delivery Vanderbilt University, Department of Chemical and Biomolecular Engineering Imaging of control drug release materials using hyperpolarised 129Xe MRI The University of Nottingham Research Fellow National University of Singapore (NUS) Postdoctoral Research Fellow Johns Hopkins University Post Doctoral Fellow, Research Associate University of Toronto More Science jobs from Drug Discovery EVENT Advances and Progress in Drug Design 18.02.14 London, UK More science events from
PERSPECTIVES		Top
OPINION The risks of risk aversion in drug regulation Hans-Georg Eichler, Brigitte Bloechl-Daum, Daniel Brasseur, Alasdair Breckenridge, Hubert Leufkens, June Raine, Tomas Salmonson, Christian K. Schneider & Guido Rasi p907 | doi:10.1038/nrd4129 Regulatory agencies have been criticized both for being overly tolerant of risks or being excessively risk-averse, but the potential for adverse effects on public health owing to the absence of new drugs because of regulatory risk-aversion is less apparent. Here, Eichler and colleagues discuss the consequences of regulatory risk-aversion and suggest what might be done to best align acceptance of risk and uncertainty by regulators with the interests of public health. Abstract | Full Text | PDF
REVIEWS		Top
Histone lysine demethylases as targets for anticancer therapy Jonas W. Højfeldt, Karl Agger & Kristian Helin p917 | doi:10.1038/nrd4154 Specific patterns of post-translational modifications in chromatin structure are important factors in the regulation of gene expression, and when deregulated they can contribute to diseases including cancer and neurological disorders. Here, Helin and colleagues focus on the role of one class of chromatin-modifier enzymes — the histone lysine demethylases — highlighting their links to cancer and their potential to be therapeutically targeted. Abstract | Full Text | PDF
Modulation of oxidative stress as an anticancer strategy Chiara Gorrini, Isaac S. Harris & Tak W. Mak p931 | doi:10.1038/nrd4002 Cancer cells have high levels of reactive oxygen species (ROS) owing to metabolic and genetic alterations. The role of ROS in cancer cells is controversial as they can have both pro-tumorigenic and antitumorigenic properties. In this Review, Mak and colleagues discuss recent findings that cancer cells upregulate antioxidant pathways to counteract ROS, and explore the potential of anticancer strategies that target the antioxidant capacity of tumour cells. Abstract | Full Text | PDF
Chemical predictive modelling to improve compound quality John G. Cumming, Andrew M. Davis, Sorel Muresan, Markus Haeberlein & Hongming Chen p948 | doi:10.1038/nrd4128 The 'quality' of small-molecule drug candidates — encompassing aspects including their potency, selectivity and pharmacokinetic characteristics — is a key factor influencing the chances of success in clinical trials. Cumming and colleagues discuss the application of computational methods, particularly quantitative structure-activity relationships, in guiding the selection of higher-quality drug candidates, as well as cultural factors that may have affected their impact. Abstract | Full Text | PDF | Supplementary information
CORRESPONDENCE		Top
Correspondence: The value of single-pathogen antibacterial agents Brad Spellberg & John H. Rex p963 | doi:10.1038/nrd3957-c1 Full Text | PDF | Supplementary information
Corrigendum: Metabolic targets for cancer therapy Lorenzo Galluzzi, Oliver Kepp, Matthew G. Vander Heiden & Guido Kroemer p963 | doi:10.1038/nrd4191 Full Text | PDF
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*2012 Journal Citation Report (Thomson Reuters, 2013)

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