Challenges of PK/PD measurements in modern drug development

Abstract

Modern cancer drug development can be characterised by a number of important principles [1–4]. These include: (1) A focus on the genes and pathways that are driving the molecular pathology and progression of human cancers, providing an intellectual framework and a source of new molecular targets for improving drug efficacy and selectivity; (2) Application of new technologies, such as high throughput screening, combinatorial chemistry and gene expression microarrays, to accelerate the discovery and development process; (3) Use of pharmacokinetic (PK) and pharmacodynamic (PD) endpoints to enhance the rationality and hypothesis-testing power of early clinical trials; and (4) Development of diagnostic, prognostic and pharmacogenomic biomarkers to allow the targeting of individualised treatments to patients most likely to benefit from a particular therapy. The exploitation of the cancer genome to discover new markers of molecular pathology, on the one hand, and novel therapeutic agents, on the other, is illustrated in Fig. 1. Against this exciting background, molecular imaging technologies have tremendous potential to impact on postgenomic drug discovery and development.