Reviews & Analysis

The challenge of predicting potential efficacy of anti-atherosclerotic drugs before the completion of long-term trials with endpoints such as mortality has stimulated efforts to develop intermediate measures of efficacy. Nissen and colleagues describe how intravascular ultrasound can be applied to the serial assessment of atheroma burden in response to treatment, which has resulted in its emergence as a key technology in the evaluation and approval of novel drugs.

Gender-specific differences in cardiovascular diseases are likely to become more important in therapeutic decisions regarding cardiovascular drug design and development. Regitz-Zagrosek reviews gender-specific differences in the most frequent cardiovascular diseases, and discusses the implications of gender-specific effects of current cardiovascular drugs.

The simplicity and cost effectiveness ofC. eleganshas made it an attractive model organism for high-throughput screening and validation of genomics-derived targets. Kaletta and Hengartner review how this simple nematode can be used in various stages of drug discovery.

Morand and colleagues review the validation of macrophage migration inhibitory factor as a therapeutic target in atherosclerosis and rheumatoid arthritis, and explore how emerging small-molecule inhibitors could address a possible mechanistic link between these diseases.

Companies can decide to pursue switches from prescription (Rx) to over-the-counter (OTC) status for their drugs for various reasons, such as life-cycle management. Mahecha examines the rationale behind switches, the switch process and case studies of switches in the United States to understand the factors for success and anticipate future trends.

fMRI is a relatively new technology that is now being evaluated for use in drug development. This has generated significant interest from biotech and pharmaceutical companies wishing to decrease the risk of drug development. Borsooket al. examine the potential use of fMRI as a tool to integrate drug development and optimize clinical development and later stage clinical trials.

The metabolic syndrome — a collection of factors associated with increased risk for cardiovascular disease and diabetes — is becoming increasingly common. Grundy summarizes the current understanding of the nature of the metabolic syndrome, and discusses each of the risk factors of the metabolic syndrome as possible drug targets.

The worldwide incidence of type 2 diabetes has reached epidemic proportions. More effective pharmaceutical options for the treatment of this devastating and costly disease are urgently needed. Dan Lazar and Alan Saltiel examine the exciting possibility that lipid phosphatases might provide a novel class of drug discovery targets for type 2 diabetes.

Advances in cellular imaging technology mean that we can now measure multiple cellular parameters at high resolution at subcellular, single-cell or cell-population level. Langet al. discuss the potential applications of this technology to drug R&D.

Multiplexed protein measurement is being established in applications such as comprehensive proteomic surveys, validation of genomic discoveries and clinical biomarker development. Kingsmore describes current and emerging multiplexed protein-measurement technologies and their applications, and discusses the challenges in this field.

Prior studies have suggested that late market entrants within a drug class frequently outperform first entrants. This idea and the general relationship between entry order and quality attributes are explored by Cohen, with a focus on the implications for innovation strategies.

Lipid II is an essential component of bacterial cell-wall biosynthesis, and as such is an attractive therapeutic target. Breukink and de Kruijff review the modes of action of compounds targeting Lipid II, and discuss their potential as treatments to combat bacterial infections.

Most monoclonal antibodies so far have been developed for treating cancer or immune disorders, but opportunities for the development of monoclonal antibodies to target infectious diseases seem to be increasing. Reichert and Dewitz analyse trends in the development of anti-infective monoclonal antibodies and discuss factors that influence their success.

Adenosine receptors have been implicated in the aetiology of various cardiovascular, inflammatory and neurological diseases. Jacobson and Gao review the development and therapeutic promise of agonists and antagonists with high selectivity for each of the four adenosine receptor subtypes.

Advances in microfluidics could prove invaluable both by enhancing existing biological assays and for the design of sophisticated new screens. Dittrich and Manz review current and future applications of scaled-down science and look at the impact of lab-on-a-chip technology on drug discovery.

Gottesman and colleagues review the most common mechanism of resistance to anticancer drugs — drug efflux from cancer cells mediated by ATP-binding cassette (ABC) transporters — and discuss various approaches to combating multidrug resistant cancer, including the development of drugs that inhibit, engage, evade or exploit efflux by ABC transporters.

For many patients with irritable bowel disease, including Crohn's disease or ulcerative colitis, existing therapies are unsatisfactory. Podolsky and Korzenik review progress in the development of new irritable bowel disease drugs including monoclonal antibodies and other biologics, and probiotic and prebiotic strategies.

Two of the newest members of the tumour-necrosis factor family, BLyS and APRIL, are crucial in B-cell development and survival, and are implicated in autoimmune diseases and cancer. Dillon and colleagues review APRIL biology, and compare potential therapeutics that target APRIL and/or BLyS.

Schizophrenia trials are subject to multiple endpoint comparison problems, the risk of false-positives, patient non-compliance, high drop-out rates and missing data. Stroup and colleagues discuss current trial limitations and how these might be addressed by innovations in trial design and statistics.

Although the prospects of gene therapy have not been fully realised, there is hope that nanotechnologies will have great impact on this field. Crommelin and colleagues describe such approaches to gene therapy. Nucleic acid delivery systems are being developed that incorporate virus-like functions in a single nanoparticle.