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Nature Reviews Drug Discovery


Implications of cancer evolution for drug development


Tumour evolution, which results in the existence of multiple distinct populations of cancer cells within the same tumour and the same patient, is increasingly appreciated to have a key role in drug resistance. In this article, we discuss the implications for drug development, including approaches to reduce the likelihood of the emergence of drug resistance.

Chinese biopharma starts feeding the global pipeline


A handful of discovered-in-China candidates have entered the global clinic, including a few first-in-class contenders.

Genetic biomarker trumps tissue type in landmark oncology approval


The FDA granted accelerated approval to Merck & Co.'s PD1 blocker pembrolizumab for all cancers with a specific genetic biomarker, regardless of which tissue type is involved. “This is an important first for the cancer community,” said the FDA's Richard Pazdur, acting director of the

Finding fault with Bial's fatal FAAH inhibitor


In January 2016, a phase I trial of Bial's oral analgesic BIA 10-2474 killed one volunteer and caused brain damage in four others. The fatal effects of the fatty acid amide hydrolase (FAAH) inhibitor may have been caused by off-target activity on several lipases,

Biotech R&D spending continues to rise


Biotech R&D spending hit US$45.7 billion in 2016, up 12% from 2015, found an annual analysis of the sector by consulting firm EY (see Fig. 1). This was the seventh consecutive year that these firms increased their cumulative R&D spending, and the second consecutive

Market watch: Landscape for medical countermeasure development


Medical countermeasures (MCMs) encompass biologics, drugs or devices that may be used for biodefence against biological, chemical or radiological bioweapons, or in the event of naturally occurring emerging and re-emerging diseases, or natural disasters. Since 2008, the Tufts Center for the Study of Drug Development

Market watch: Upcoming market catalysts in Q3 2017


Market catalysts in the third quarter of 2017 include top-line phase III trial results for several therapeutics: patisiran (developed by Alnylam Pharmaceuticals) for the treatment of hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN); durvalumab (developed by AstraZeneca) for the first-line treatment of locally advanced or metastatic

Yong-Jun Liu


Yong-Jun Liu is a drug discovery veteran with a career that has spanned both academia and industry. Since 2002 he has overseen drug discovery programmes at the University of Texas MD Anderson Cancer Center, Baylor Research Institute and AstraZeneca's biologics company MedImmune. He added another large pharma firm to this roster in 2016, when he joined Sanofi as head of research. Sanofi's president of global R&D Elias Zerhouni prioritized the development-stage pipeline during the first years of his tenure at the company, but brought Liu on board last year to refocus on the internal early-stage drug discovery efforts. Liu spoke with Asher Mullard about his first year at Sanofi and the company's emphasis on multi-targeted therapeutics.

The ovarian cancer drug market


This article discusses the impact of the recent approvals of poly ADP ribose polymerase (PARP) inhibitors on the market for ovarian cancer drugs, as well as potential future treatments such as immunotherapies.

Cardiovascular disease: BET inhibitor attenuates heart failure


Heart failure (HF) is a leading cause of mortality and hospitalization. Writing in Science Translational Medicine, Duan and colleagues demonstrate that inhibition of bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extraterminal domain (BET) family of epigenetic signalling proteins, reduces pathology and

Endocrinology: Reducing fat and building bone


Menopause — characterized by an increase in circulating levels of follicle-stimulating hormone (FSH) and a decline in oestrogen due to ovarian failure — is associated with loss of bone mass and increased visceral adiposity. Although treatments for osteoporosis and obesity exist, their use may be

Transporters: Natural product provides alternative transport for iron


Deficiencies in passive ion-transport proteins give rise to a range of diseases, including anaemias, cystic fibrosis and cardiac arrhythmias. A recent paper in Science has demonstrated that a small-molecule natural product, hinokitiol, transports iron across cell membranes and restores iron handling in several animal

Cancer immunotherapy: Macrophages steal the show


The past decade has seen remarkable advances in tumour immunology due to extensive research on inhibition of programmed cell death protein 1 (PD1) — which is expressed on T cells — and its ligand PDL1, which is expressed on tumour cells. However, little is known

Cancer: Targeting MYC-driven translation


Overactivity of the transcription factor MYC plays a central part in the progression of multiple myeloma through upregulation of ribosome synthesis and translation activity. Using a high-throughput screening approach, Manier et al. have identified a series of synthetic analogues of the rocaglate natural product

Genetic disorders: Repurposing metformin in FXS


Fragile X syndrome (FXS) is caused by loss of the fragile X mental retardation 1 (FMR1) gene and is characterized by learning disabilities and cognitive impairment. Here, Gantois et al. have shown that injection of the type 2 diabetes therapeutic metformin for

G Protein-Coupled Receptors: Crystal structure of glucagon family receptors


The class B G protein-coupled receptors (GPCRs), glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R), have key roles in glucose homeostasis and therefore represent valuable drug targets for diabetes. Zhang et al. now report the crystal structure of the full-length human GCGR in

Ageing: Old bone removal


Senescent cells (SNCs), which accumulate in many tissues with age, contribute to several age-related pathologies. Now, Elisseeff and colleagues have shown that the selective elimination of SNCs with a specific inhibitor (UBX0101) of the anti-apoptotic protein mouse double minute 2 (MDM2) can prevent and even

Different drugs for bad bugs: antivirulence strategies in the age of antibiotic resistance


The rapid evolution and dissemination of antibiotic resistance among bacterial pathogens are outpacing the development of new antibiotics, but antivirulence agents provide an alternative. These agents can circumvent antibiotic resistance by disarming pathogens of virulence factors that facilitate human disease while leaving bacterial growth pathways

Targeting glutamate signalling in depression: progress and prospects


Major depressive disorder (MDD) is severely disabling, and current treatments have limited efficacy. The glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine was recently repurposed as a rapidly acting antidepressant, catalysing the vigorous investigation of glutamate-signalling modulators as novel therapeutic agents for depressive disorders.

Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles


Autophagy is central to the maintenance of organismal homeostasis in both physiological and pathological situations. Accordingly, alterations in autophagy have been linked to clinically relevant conditions as diverse as cancer, neurodegeneration and cardiac disorders. Throughout the past decade, autophagy has attracted considerable attention as a