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This Opinion highlights some of the recent failures in the clinical trials of chemokine receptor antagonists, explores possible reasons as to why these might have occurred and looks at potential solutions to generate effective chemokine receptor antagonist therapeutics.
The p53 tumour suppressor pathway is an attractive target for the development of anticancer therapies. This Perspective highlights recent progress with agents that modulate components of the p53 pathway — in particular, p53 itself and its negative regulator MDM2 — focusing on how studies of their genetic variations, including mutations in cancer cells and inherited polymorphisms, could help tailor the use of existing agents and aid the development of novel drugs.
Despite improvements in European regulatory standards and procedures, the occurrence of failed or problematic marketing authorization applications for biotechnological products remains common. Here, Schäffner-Dallmann and Schneider identify common regulatory concerns and consider strategies that may help prevent such issues.
The association of genetic profiles to drug response is helping to expedite the development of new drugs and diagnostic tests. Roses discusses the considerations that have to be taken into account when identifying pharmacogenetic variants associated with responses to drugs and designing clinically relevant tests.
Drug regulatory agencies face the challenge of striking the appropriate balance between the need for rapid access to new drugs and the need to obtain comprehensive data on their benefit/risk profiles. This article highlights the scientific and regulatory issues involved, discusses regulatory strategies to address these issues, and speculates on future directions, such as a life-cycle approach to drug regulation.
In the past decade, the ability of nuclear magnetic resonance (NMR) spectroscopy to provide information on intermolecular interactions that is valuable in drug discovery has been increasingly appreciated. Pellecchia and colleagues provide their collective evaluation of the major applications of NMR in drug discovery, focusing on hit and lead generation, and critically analyse its current and potential utility.
Neuroprotective agents that slow cell death, vital for the treatment of a range of neurodegenerative disorders, are currently lacking. Dragunow discusses some of the factors contributing to the failure of translation from the laboratory to the clinic, and suggests approaches to introduce an adult human preclinical platform to overcome translation obstacles in neurodegenerative drug development.
In this Perspective, Max and Stewart discuss how methods of molecular epidemiology, proved effective in the study of other diseases, can enhance the returns from human genomic studies and expedite the development of new drugs to prevent or treat pain.
Recent advances in genomic knowledge and associated technologies should help accelerate the development of genetic tests that can predict drug response and toxicity; however several challenges remain. Here, Weiss and colleagues discuss the factors that affect the development, performance and uptake of pharmacogenetic tests.
Katz and colleagues summarize knowledge on associations between drug pharmacokinetics and variations in genes coding for proteins involved in drug disposition. They propose a novel strategy in which pharmacogenetic data from early clinical studies is used both to feed back to furtherin vitrostudies of drug pharmacokinetics and to feed forward to optimize later-stage clinical trials, and discuss how this could improve drug development.
In this article, Dobson and Kell discuss the evidence to support the idea that carrier-mediated and active uptake of drugs may be more common than is usually assumed and consider the implications for drug discovery and development.
The emerging influence of intestinal microorganisms on human health has led to the prospect of modulating gut microbiota composition as a novel therapeutic strategy. In this article, Jia and colleagues discuss the rationale behind this approach, identify conditions to which this may be applied, and suggest technologies and strategies for the development of gut microbiota-targeted therapies.
The number and frequency of use of protein therapeutics has increased dramatically since the introduction of the first recombinant protein therapeutic — human insulin — 25 years ago. Golan and colleagues overview some of the key characteristics of protein therapeutics, summarize the more than 130 protein therapeutics used currently and suggest a new classification of these proteins based on their pharmacological action.
