Nature Reviews Drug Discovery contents March 2018 Volume 17 Number 3 pp 151-223

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TABLE OF CONTENTS
March 2018 Volume 17 Number 3		Advertisement
2016 2-year Impact Factor 57.000 Journal Metrics 2-year Median 38	In this issue Comment News and Analysis Research Highlights Perspectives Reviews   Also this month  Featured article: Next generation antibody drugs: pursuit of the 'high-hanging fruit' Paul J. Carter & Greg A. Lazar	Do you have a career question? The Naturejobs podcast features one-on-one Q&As, panel discussions and other exclusive content to help scientists with their careers. Hosted on the Naturejobs blog, the podcast is also available on iTunes and Soundcloud.  Listen today!
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Thinking Outside the ATP Box: New Ways to Target Kinases for Therapeutics  May 22, 2018, NYC Nathanael S. Gray of Harvard Medical School joins other top experts for a one-day symposium exploring emerging approaches to advance the discovery of novel non-classical kinase inhibitors. Abstract deadline March 23rd. Find more information and register here.
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Nature Outlook: Fatty liver disease The worldwide rise in obesity and diabetes has led to a spike in non-alcoholic fatty liver disease, which often progresses to the more severe non-alcoholic steatohepatitis. This Outlook discusses new diagnostic techniques and therapies.  Access the Outlook free online >>  Produced with support from:  Gilead Sciences
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Comment: Addressing challenges in the diagnosis and treatment of rare genetic diseases Kym M. Boycott & Diego Ardigo p151 | doi:10.1038/nrd.2017.246 The past 5 years have seen an unprecedented rate of discovery of genes that cause rare diseases and with it a commensurate increase in the number of diagnosable but nevertheless untreatable disorders. Here, we discuss the increasing opportunity for diagnosis and therapy of rare diseases and how to tackle the associated challenges. Abstract | Full Text | PDF
NEWS AND ANALYSIS		Top
Oncologists tap the microbiome in bid to improve immunotherapy outcomes Asher Mullard p153 | doi:10.1038/nrd.2018.19 A pioneering Merck & Co.-funded study is set to explore the ability of the microbiome to boost immuno-oncology therapy outcomes, and other companies are quickly gearing up to enter this clinical space. PDF
Alnylam prepares to land first RNAi drug approval Chris Morrison p156 | doi:10.1038/nrd.2018.20 With Alnylam's rare disease drug candidate patisiran nearing the regulatory finish line, the RNA interference community is now turning its attention to next-generation delivery technology to solidify the future of the emerging modality. PDF
AN AUDIENCE WITH Fiona Marshall p158 | doi:10.1038/nrd.2018.25 Fiona Marshall — co-founder of Heptares, former chief scientific officer of Sosei and soon to be lead of Merck & Co.'s new research facility in London — looks back on 30 years of GPCRs, and looks forward to the emerging therapeutic opportunities these targets still offer. PDF
FROM THE ANALYST'S COUCH The market for chimeric antigen receptor T cell therapies Amy Yip & Rachel M. Webster p161 | doi:10.1038/nrd.2017.266 This article discusses the market for chimeric antigen receptor (CAR) T cell therapies, focusing on haematological malignancies. PDF
RESEARCH HIGHLIGHTS   Top Cancer: Fibroblast subtype provides niche for cancer stem cells p163 | doi:10.1038/nrd.2018.23 PDF Cancer: New path to improving immunotherapy p164 | doi:10.1038/nrd.2018.22 PDF Immunotherapy: Direct shot p165 | doi:10.1038/nrd.2018.29 PDF Cancer: Reset your circadian clock p166 | doi:10.1038/nrd.2018.24 PDF   IN BRIEF Cardiovascular disease: Inhalation therapy for heart failure | Antibacterials: Synthetic peptides eradicate resistant infections | Alzheimer disease: Identification of blood-based biomarkers | Cancer: Targeting the ubiquitin pathway PDF Drug Discovery JOBS of the week Postdoctoral Fellow Position Available National Cancer Institute (NCI) Research Fellow X 2 (Level A or Level B) Monash University Postdoctoral Fellow Position Available National Institutes of Health (NIH), Department of Health and Human Services (HHS) Associate Principle Scientist, Inform & Analytics Merck Sharpe & Dohme Corp. Postdoctoral Associate University of Minnesota - College of Pharmacy More Science jobs from Drug Discovery EVENT G36 Effective Project Management for Clinical Trials 06.11.18 Maidenhead, UK More science events from
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Nature Collection: 2017 Nobel Prize in Physiology or Medicine The 2017 Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their pioneering work in Drosophila that elucidated the molecular mechanisms controlling circadian rhythm.  Access this collection free online>> Produced with support from:  Vanda Pharmaceuticals
PERSPECTIVES		Top
OUTLOOK Impact of a five-dimensional framework on R&D productivity at AstraZeneca Paul Morgan, Dean G. Brown, Simon Lennard, Mark J. Anderton, J. Carl Barrett, Ulf Eriksson, Mark Fidock, Bengt Hamrén, Anthony Johnson, Ruth E. March, James Matcham, Jerome Mettetal, David J. Nicholls, Stefan Platz, Steve Rees, Michael A. Snowden & Menelas N. Pangalos p167 | doi:10.1038/nrd.2017.244 In 2011, AstraZeneca set out to improve its research and development (R&D) productivity by focusing decision-making using a framework with five technical determinants: the right target, right tissue, right safety, right patient and right commercial potential. Here, Pangalos and colleagues describe the progress made using this '5R framework', with metrics indicating improved success rates, and discuss where the approach has failed and the lessons learned. Abstract | Full Text | PDF | Supplementary information
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Drug development in the era of precision medicine Sarah A. Dugger, Adam Platt & David B. Goldstein p183 | doi:10.1038/nrd.2017.226 The contribution of genomics to drug discovery and development so far has not yet lived up to the initial high expectations. Goldstein and colleagues discuss the reasons for the limited progress and review how recent advances — particularly in oncology and rare genetic diseases — may enable precision medicine strategies to harness the therapeutic potential of genomic knowledge. Abstract | Full Text | PDF
Next generation antibody drugs: pursuit of the 'high-hanging fruit' Paul J. Carter & Greg A. Lazar p197 | doi:10.1038/nrd.2017.227 Antibody therapeutics are now established as a major drug class. Here, Carter and Lazar comprehensively discuss current and emerging platforms and technologies for antibody therapeutics, with an emphasis on approaches that could extend their therapeutic applications, including antibody-drug conjugates, bispecific antibodies and antibody engineering to enable more effective delivery. Abstract | Full Text | PDF
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