Review Articles in 2007

The cellular microenvironment plays a critical role in cellular responses to therapy. A greater understanding of the extracellular matrix (ECM) and ECM–cell interactions could facilitate the design of novel drug delivery systems for biomacromolecular therapies, and interventions to manipulate the microenvironment may further improve the efficiency of such therapies.

Aggregation of hyperphosphorylated tau is involved in neurodegeneration in Alzheimer's disease and other disorders. The authors discuss the progress in the design of selective kinase inhibitors that suppress tau hyperphosphorylation as a therapeutic strategy for neurodegenerative tauopathies.

Although clinical trials using matrix metalloproteinase inhibitors (MMPIs) for cancer therapy were disappointing, Opdenakker and colleagues discuss how the use of selective MMPIs might lead to new treatments for acute and chronic inflammatory and vascular diseases.

Dual-specificity phosphatases (DUSPs) are a subclass of protein tyrosine phosphatases (PTPs) that interact with and regulate mitogen-activated protein kinases (MAPKs). DUSPs can positively or negatively control immune responses in cancers, infectious diseases and inflammatory diseases, making them promising drug targets for immune-based disorders.

Ten years after the cloning of the capsaicin TRPV1 receptor, TRPV1 antagonists are currently in clinical trials for the treatment of pain. Szallasi and colleagues review the past decade of progress and discuss how TRPV1 antagonists could be beneficial in other disorders.

Endogenous polyamines are essential for cell growth and are known to be dysregulated in cancer and other diseases. Here the potential strategies for modulating polyamine metabolism and function are reviewed with a focus on the use of synthetic polyamine analogues.

Peptide epitopes represent the minimal immunogenic region of a protein antigen. In the light of new insights into the nature of immunogenic epitopes, and recent advances in peptide delivery, stability and design, Purcell and colleagues review developments in the field of peptide-based vaccines.

In this Review, Pettipher and colleagues discuss antagonism of DP₁ and CRTH2 prostaglandin D₂receptors as an approach to treat allergic diseases. They also review recent progress in the discovery and development of selective antagonists of these receptors.

The process of autophagy has recently sparked great interest as it is recognized to be involved in a wide range of diseases. The prospect of its manipulation for therapeutic purposes has led to the discovery of many exciting new potential drug targets.

Biomarkers to diagnose neurodegenerative disorders early in their course and to monitor responses of patients to therapeutic interventions are urgently needed to optimize the development and application of novel disease-modifying drugs. Trojanowski and colleagues discuss progress and key issues in the discovery and validation of such biomarkers, with a focus on Alzheimer's disease.

Lipophilic, poorly water-soluble drug candidates are common outcomes of drug discovery programmes. Porter and colleagues discuss mechanisms by which lipids and lipidic excipients can improve oral absorption of lipophilic drugs, and provide a perspective on the future applications of lipid-based delivery systems.

In this Review, Loging and colleagues discuss how high-throughput techniques in electronic biology can utilize the vast range of life sciencein silicoresources, and examine how best to apply these techniques to aid the drug discovery process.

Fragment-based drug design involves screening a small number of low-molecular-mass compounds with the aim of identifying low-affinity 'fragments' that are well-suited for optimization into more potent compounds. Hajduk and Greer describe the evolution of this approach into a valuable alternative to high-throughput screening for the discovery of lead compounds, and highlight lessons learned from its application over the past decade.

New therapeutic strategies are needed to improve the cure rate and quality of life in patients with acute lymphoblastic leukaemia. In this Review, Pui and Jeha discuss emerging new treatments that could improve the clinical outcome for these patients.

Being able to predict the individual effects of drugs on different patients in a population could lead to safer, more effective medicines. The authors discuss the development of algorithms that could enable the testing of drugs in virtual patient populations based onin vitrodata.

There is a major need for better therapies for many patients with heart failure, but late-stage clinical failures of several potential drugs have reduced the impetus of drug development in this field. Kaye and Krum review emerging agents and molecular targets for heart failure, and highlight key issues that need to be addressed to improve the chances of successfully developing new drugs.

The debate about whether truly novel, tractable targets exist for antibacterial drug discovery continues. Meanwhile, as Lynn Silver discusses, efforts are focused on learning from the 'good old targets' to improve current antibiotic classes and develop antibacterial strategies for the future.

The potential for using the lungs as a gateway for delivering drugs to the systemic circulation is attracting increasing attention. Here, Patton and Byron review current issues in the formulation and systemic delivery of small molecules and macromolecules as inhaled therapeutics.

Clinical use of biologic therapies for rheumatology has revealed that efficacy, toxicity and pharmacodynamic effects can deviate from those predicted. In this review, Issacs and colleagues summarize lessons gleaned from practical experience and discuss how these can inform future development of new biologic therapies.