Nature Genetics is pleased to present the iCOGS print and online Focus advancing our understanding of the genetic susceptibility to three common hormone-related cancers-breast, ovarian and prostate cancers. This collection of 13 papers by the COGS (Collaborative Oncological Gene-environment Study) Consortium is accompanied by editorial essays highlighting and analyzing the main themes of this milestone in genetic epidemiology.
US clinical-research system in need of review doi:10.1038/498007a An imminent rethink is required on the country's approach to government-supported health and pharmaceutical studies. Full Text
'Basket studies' will hold intricate data for cancer drug approvals doi:10.1038/nm0613-655 Researchers weave a new trial design on the basis of genetics, rather than cancer type. Full Text
An audience with Menelas Pangalos doi:10.1038/nrd4044 Menelas Pangalos, Executive Vice President of Innovative Medicines at AstraZeneca, discusses the company's R&D strategy. Full Text
Patent watch: One valid claim is all that is needed doi:10.1038/nrd4049 Allergan still has patent protection for its glaucoma drug Combigan (brimonidine and timolol) even though a US court ruled that a patent that describes the combination of brimonidine and timolol is obvious. Full Text
What matters most in commercial success: first-in-class or best-in-class? doi:10.1038/nrd4035 Given that it is common for several companies to be simultaneously pursuing promising new targets, this analysis investigates the question of whether it is better to be first or best in a particular new class of drugs. Full Text
Driving cancer through ErbB3 doi:10.1038/scibx.2013.535 Genentech researchers show that mutations in ERBB3 can drive oncogenesis in a process dependent on the receptor's ability to form a heterodimer with HER2. The findings suggest existing HER2-targeted therapies also could be effective against cancers driven by mutations in ERBB3. Full Text
Inflammatory disorders: Targeting TRAFs tames inflammation doi:10.1038/nrd4029 Inhibition of tumour necrosis factor receptor-associated factors (TRAFs) through FBX03 could represent a novel potential anti-inflammatory therapeutic strategy. Full Text
G protein-coupled receptors: Pioneering Frizzled family receptor structure solved doi:10.1038/nrd4030 A crystal structure of the human Smoothened (SMO) receptor — an essential component of the Hedgehog signalling pathway — bound to an antitumour compound has been solved. Full Text
Analgesia: A new player in neuropathic pain pathogenesis doi:10.1038/nrd4031 The WNT family of proteins, which are involved in the regulation of cellular processes during nervous system development, have a key role in the pathogenesis of neuropathic pain. Full Text
Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases doi:10.1038/nrd4010 Although nucleoside analogues have been used clinically for decades, efforts continue to improve response rates and reduce side effects. This article highlights recent progress in the development of new nucleoside and nucleotide analogues for cancer and viral diseases. Full Text
The emerging mutational landscape of G proteins and G-protein-coupled receptors in cancer doi:10.1038/nrc3521 This article discusses deep sequencing studies indicating that nearly 20% of human tumours harbour mutations in G-protein-coupled receptors (GPCRs) and the implications for GPCRs as therapeutic targets in oncology. Full Text
The good, the bad and the ugly – TFH cells in human health and disease doi:10.1038/nri3447 An increasing number of studies have highlighted new aspects of the differentiation and function of T follicular helper (TFH) cells in disease, which might represent targets for novel therapeutics. Full Text
Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling doi:10.1038/nature12205 Interfering with binding of PDEδ to KRAS with small molecules provides a novel opportunity to suppress oncogenic RAS signalling by altering its localization to endomembranes. Full Text
Career snapshots archive Career snapshots feature people associated with drug discovery and drug development, with the aim of providing expert insights and advice on a wide range of positions and career paths in this field. Full Text
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