Table of Contents
ISRN Pharmacology
Volume 2012, Article ID 590626, 12 pages
http://dx.doi.org/10.5402/2012/590626
Review Article

Pharmacodynamic Modelling of Biomarker Data in Oncology

Pharmacometrics Ltd., Whittlesford, Cambridge CB22 4NZ, UK

Received 5 November 2011; Accepted 6 December 2011

Academic Editors: S. Cuzzocrea and E. M. Urbanska

Copyright © 2012 Robert C. Jackson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The development of pharmacodynamic (PD) biomarkers in oncology has implications for design of clinical protocols from preclinical data and for predicting clinical outcomes from early clinical data. Two classes of biomarkers have received particular attention. Phosphoproteins in biopsy samples are markers of inhibition of signalling pathways, target sites for many novel agents. Biomarkers of apoptosis in plasma can measure tumour cell killing by drugs in phase I clinical trials. The predictive power of PD biomarkers is enhanced by data modelling. With pharmacokinetic models, PD models form PK/PD models that predict the time course both of drug concentration and drug effects. If biomarkers of drug toxicity are also measured, the models can predict drug selectivity as well as efficacy. PK/PD models, in conjunction with disease models, make possible virtual clinical trials, in which multiple trial designs are assessed in silico, so the optimal trial design can be selected for experimental evaluation.