Reviews & Analysis

Predictive biomarkers allow the identification of the subsets of patients who will benefit from a particular drug. However, the development of biomarker–drug combinations requires novel clinical trial designs. In their Perspective, Beckman and colleagues formulate guidelines for the adaptive integration of predictive biomarkers into Phase II/Phase III clinical trials and present strategies to achieve optimal efficiency of such trials.

Analysing data on bioactive compounds can provide insight for developing improved molecules, although much of this data currently resides in proprietary databases. However, even when such data is made available in research articles or public databases, key information is often missing, or the data is not in a format suited to data-mining. With the aim of addressing these issues, this article proposes reporting guidelines for bioactive entities, which have been developed by representatives from industry, academia and data resource providers.

The efficacy–effectiveness gap describes the difference in drug performance under clinical trial conditions versus real-life conditions. Here, the authors argue that this phenomenon is due to variability in drug responses. They discuss the underlying biological and behavioural reasons for this phenomenon and propose strategies to 'bridge the gap'.

Vessel normalization strategies aim to increase tumour perfusion and oxygenation, and have the potential to reduce metastasis and improve responses to conventional anticancer therapies. Here, Carmeliet and Jain discuss the benefits and limitations of this emerging new treatment paradigm for cancer and other angiogenic disorders.

G-quadruplexes are four-stranded DNA structures that appear to be over-represented in the promoter region of various genes, including oncogenes such asMYC and KRAS. This article discusses evidence indicating the possibility of therapeutically modulating the transcription of such genes through the targeting of G-quadruplexes with small molecules, and considers challenges and opportunities for the development of such molecules as anticancer drugs.

The reduction in attrition rates of cancer therapeutics in the clinic requires robust translational strategies. In their Perspective, Caponigro and Sellers review historical and current uses of preclinical model systems, and discuss how these systems can be optimized for rationally predicting the therapeutic benefit of drug candidates.

Has high-throughput screening (HTS) been unfairly blamed one factor responsible for the decline in productivity in the pharmaceutical industry? This article discusses some common misconceptions about the nature and value of HTS, and argues in support of its importance as a key tool in the discovery of novel chemotypes in drug discovery and chemical biology.

The Fc (crystallizable fragment) region of therapeutic antibodies can have an important role in their safety and efficacy. This article summarizes the current knowledge of antibody Fc functionality, provides a strategy for assessing the effector functions of different classes of therapeutic antibodies and proposes a path for routine testing and controls for manufacturers of antibody products.