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Pharmacodynamic Modelling of Biomarker Data in Oncology
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 ma...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scholarly Research Network
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302113/ https://www.ncbi.nlm.nih.gov/pubmed/22523699 http://dx.doi.org/10.5402/2012/590626 |
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author | Jackson, Robert C. |
author_facet | Jackson, Robert C. |
author_sort | Jackson, Robert C. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3302113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | International Scholarly Research Network |
record_format | MEDLINE/PubMed |
spelling | pubmed-33021132012-04-20 Pharmacodynamic Modelling of Biomarker Data in Oncology Jackson, Robert C. ISRN Pharmacol Review Article 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. International Scholarly Research Network 2012-02-16 /pmc/articles/PMC3302113/ /pubmed/22523699 http://dx.doi.org/10.5402/2012/590626 Text en 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. |
spellingShingle | Review Article Jackson, Robert C. Pharmacodynamic Modelling of Biomarker Data in Oncology |
title | Pharmacodynamic Modelling of Biomarker Data in Oncology |
title_full | Pharmacodynamic Modelling of Biomarker Data in Oncology |
title_fullStr | Pharmacodynamic Modelling of Biomarker Data in Oncology |
title_full_unstemmed | Pharmacodynamic Modelling of Biomarker Data in Oncology |
title_short | Pharmacodynamic Modelling of Biomarker Data in Oncology |
title_sort | pharmacodynamic modelling of biomarker data in oncology |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302113/ https://www.ncbi.nlm.nih.gov/pubmed/22523699 http://dx.doi.org/10.5402/2012/590626 |
work_keys_str_mv | AT jacksonrobertc pharmacodynamicmodellingofbiomarkerdatainoncology |