Pharmacogenetic biomarkers for the prediction of response to antiangiogenic treatment

Abstract

Antiangiogenic treatments have shown activity across multiple tumour types and in various settings. Despite having been approved on the basis of efficacy, the therapeutic index varies substantially in different settings for many of these agents. A major limitation is the current inability to personalise treatment a priori according to findings on measurement of a predictive biomarker. The roles of germline single-nucleotide polymorphisms have been investigated as potential biomarkers for antiangiogenic treatments. The rationale is founded on the understanding that the drugs target the vasculature rather than the tumour, which could mean that much of the variability is regulated by the host. Several single-nucleotide polymorphisms have been associated with differential outcomes and toxic effects in clinical trials. In this Review we provide an overview of available data with particular attention paid to the pitfalls and strengths of potential biomarkers. We also highlight continuing work and plans for confirmatory studies.