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Nature Reviews Drug Discovery


Lessons from immuno-oncology: a new era for cancer nanomedicine?


Despite a decade of intensive preclinical research, the translation of cancer nanomedicine to the clinic has been slow. Here, we discuss how recent lessons learned from the successes with immuno-oncology therapies could be applied to cancer nanomedicine and how this may help to overcome some

Zeroing in on neurodegenerative α-synuclein


In the search for the first disease-modifying therapy for Parkinson disease, drug developers are advancing α-synuclein-targeted agents into proof-of-concept clinical trials.

Search for liquid biopsy grail points the way to drug discovery and development gems


An emerging technology for early cancer diagnosis could lead to innovative clinical trial strategies, novel drug combinations and new drug targets.

Immuno-oncology upset in bladder cancer


Roche and Genentech's checkpoint inhibitor atezolizumab did not improve overall survival in a confirmatory phase III trial in patients with advanced bladder cancer. The FDA granted accelerated approval to the anti-programmed cell death protein 1 ligand 1 (PDL1) antibody for this indication in 2016

FDA approves first new ALS drug in over 20 years


The FDA approved Mitsubishi Tanabe Pharma's edaravone for amyotrophic lateral sclerosis (ALS), the first US approval for the deadly neurodegenerative disease since riluzole in 1995.ALS is a rare disease that attacks and kills the nerve cells that control voluntary muscles, affecting the ability

FDA approves first targeted drug for acute myelogenous leukaemia


The FDA approved Novartis's FLT3 inhibitor midostaurin for acute myeloid leukaemia (AML). The multikinase inhibitor is the first targeted treatment for AML, and the first new FDA approval for AML in decades.The FLT3 kinase is mutated in around one-third of AML patients, and

Market watch: Trends in pharmaceutical company R&D spending: 2005–2015


Pharmaceutical industry trade groups commonly claim that growing revenues (supported by premium prices) are required to drive innovative R&D, whereas critics maintain that drug companies' outsized returns mainly support corporate infrastructures, fuel marketing budgets and enrich investors. In fact, both arguments are incompletely supported by

Deal watch: Neurokinin 3 receptor antagonist revival heats up with Astellas acquisition


Japan's Astellas Pharma has announced that it will acquire the Belgian biotech Ogeda for up to [euro]800 million, including milestone payments (Fig. 1). Ogeda's sole clinical asset, fezolinetant, is a small-molecule inhibitor of the neurokinin 3 receptor (NK3R), for which the company reported

Birgitte Volck


Small patient populations are big business. In 2000, worldwide sales of orphan drugs for rare diseases accounted for just 6% of global prescription drug sales. Last year they accounted for US$114 billion in revenue and nearly 16% of total prescription drug sales, and they are on track to account for 21% of sales by 2022. For Birgitte Volck, head of rare disease R&D at GlaxoSmithKline, the explosion of this space has tracked with the arrival of a new era in rare disease drug discovery and development. She told Asher Mullard about how new drug modalities, the voice of the patient and genomics are reshaping the field.

How much do clinical trials cost?


This article presents the findings of a recent analysis of the costs of clinical trials, providing benchmark data for companies to assess their performance, as well as indicating cost drivers.

Cancer immunotherapy: T cells get a ride


Strategies that inhibit the immune checkpoint blockade (ICB) and reactivate T cells using monoclonal antibodies against programmed cell death protein 1 (PD1) and PD1 ligand 1 (PDL1) have been used to successfully treat immunogenic tumours, and recent efforts have focused on combining this approach with

Neurodegenerative disorders: Ataxin 2 reduction rescues motor defects


Mutations in ATXN2, the gene encoding ataxin 2 — an RNA-binding protein found throughout the body with multiple roles in RNA metabolism — have been implicated in both amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (SCA2). Writing in Nature, two new

Ageing: A youthful reminder


In rodents, the introduction of blood from young to old animals can reverse some of the negative effects that ageing exerts on CNS function, including detrimental changes in hippocampal function. However, it is not known which molecules found in young blood exert such effects or

Neurological disorders: DAMPening damage after stroke


Much of the tissue injury that occurs following ischaemic stroke is caused by sterile inflammation, which lasts for about a week after the initial artery blockade. Shichita and colleagues have found that increasing transcription of macrophage scavenger receptor 1 (Msr1) reduced neurological deficits

Inflammation: Oncostatin M blockade attenuates colitis


Anti-tumour necrosis factor (TNF) antibodies represent established therapies for inflammatory bowel disease (IBD), but up to 40% of patients exhibit primary nonresponsiveness to anti-TNF agents, and resistance can develop. West et al. observe high levels of the cytokine oncostatin M (OSM) and its receptor

Infectious disease: Peroxin inhibitor treats Trypanosoma infection


Insect-borne Trypanosoma spp. parasites transmitted predominantly by the tsetse fly infect humans as well as livestock, which causes devastating diseases, such as human African trypanosomiasis (HAT) and Chagas disease. Current treatments for trypanosomiases are limited, can cause serious side effects and require long treatment

Metabolic disease: PGC1α inhibition ameliorates diabetes


Peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α) plays a pivotal part in energy homeostasis and is involved in the regulation of gluconeogenesis. Using a cell-based high-throughput chemical screen, Sharabi et al. have identified a small molecule, SR-18292, that increases acetylation of PGC1α, which results in

Ageing: FOXO4 inhibition eliminates senescent cells


Senescent cells exhibit a pro-inflammatory phenotype, and are thought to accelerate ageing and the onset of age-related diseases. Baar et al. report a key role for forkhead box protein O4 (FOXO4) in maintaining senescent cell viability. In vitro, a FOXO4-derived peptide designed to

Cystic fibrosis: Thymosin α1 rescues CFTR activity


Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein and is characterized by chronic lung inflammation. Romani et al. show that the naturally occurring polypeptide thymosin α1 — clinically used as an immunotherapeutic agent —

Delivery technologies for genome editing


With the recent development of CRISPR technology, it is becoming increasingly easy to engineer the genome. Genome-editing systems based on CRISPR, as well as transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs), are becoming valuable tools for biomedical research, drug discovery and development, and

Targeting iron metabolism in drug discovery and delivery


Iron fulfils a central role in many essential biochemical processes in human physiology; thus, proper processing of iron is crucial. Although iron metabolism is subject to relatively strict physiological control, numerous disorders, such as cancer and neurodegenerative diseases, have recently been linked to deregulated iron

Non-kinase targets of protein kinase inhibitors


Kinome-wide profiling platforms have comprehensively identified the relevant kinases that are targeted by numerous protein kinase inhibitors. However, recent projects have begun to discover non-kinase targets of kinase inhibitors. These non-kinase targets can contribute to the desired or undesired activities of inhibitors, or act as

Aptamers as targeted therapeutics: current potential and challenges


Nature Reviews Drug Discovery16, 181–202 (2017)Base Pair Biotechnologies and Apterna were omitted from Table 3 in this article. These have now been included.