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The central roles of members of the fibroblast growth factor (FGF) family in human developmental processes and disease have been well documented. In their Review, Beenken and Mohammadi discuss the more established applications of FGF-related therapies in the treatment of cancer and cardiovascular disease, emphasizing their potential to modulate aspects of the metabolic syndrome and hypophosphataemic diseases.
The field of cancer chemoprevention has reported its first major successes, but broad translation to the clinic is not yet a reality. Here, Lippman and colleagues review the unique challenges encountered in this field, and the promise of personalized, molecularly targeted chemoprevention strategies.
Oligosaccharides are key to the mode of action of recombinant monoclonal antibodies. This article reviews current understanding of the role of antibody glycosylation on antibody effector function and the strategies that are being explored to produce homogeneous natural antibody glycoforms with optimized therapeutic efficacy.
Recent clinical trials have raised questions about the perceived advantages of second-generation 'atypical' antipsychotics over older drugs. This article discusses how broadening of the concept of 'atypicality' — originally related purely to a lack of extrapyramidal side effects — might have hampered the search for better antipsychotics, and proposes that redefining the concept could be key for breakthroughs in schizophrenia therapy.
RNA interference holds vast potential as a therapeutic strategy for both disease prevention and treatment, but its use has so far been hampered by a lack of safe and effective delivery techniques. In their Review, Anderson and colleagues discuss the challenges associated with small interfering RNA delivery and highlight promising novel synthetic delivery agents.
The recent discovery of a new family of oxygen sensors — including prolyl hydroxylase domain-containing proteins 1–3 (PHD1–3) — has provided novel insights into how cells sense oxygen and keep oxygen supply and consumption in balance. This review describes how advances in understanding of the role of these oxygen sensors in hypoxia tolerance, ischaemic preconditioning and inflammation are creating new opportunities for pharmacological interventions in ischaemic and inflammatory diseases.
Transient receptor potential (TRP) channels are the most prominent family of nociceptive ion-channel transducer proteins. This Review highlights evidence supporting particular TRP channels as targets for analgesics, indicates the likely efficacy profiles of TRP-channel-acting compounds and looks at recent clinical trials with TRP-channel-acting drugs.
The nuclear factor κB (NF-κB) signalling pathway has been implicated in cancer development and progression, as well as in resistance to chemotherapy and radiation therapy. In this Perspective, Baud and Karin explore the therapeutic potential of targeting NF-κB in cancer, and discuss the challenges posed by this approach.
G protein–coupled receptors (GPCRs) represent one of the most targeted protein families in pharmaceutical research. Traditionally, drug discovery programmes have searched for ligands that act at endogenous orthosteric sites. Here, Conn and colleagues discuss recent advances in the identification of novel GPCR ligands that act at allosteric sites, highlighting their potential in the treatment of psychiatric and neurological disorders.
