Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials

Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials

Anti-cancer clinical drug development is currently costly and slow with a high attrition rate. There is thus an urgent and unmet need to integrate pharmacodynamic biomarkers into early phase clinical trials in the framework provided by the “pharmacologic audit trail” in order to overcome this challe...

Full description

Bibliographic Details
Main Authors: Ang, Joo Ern, Kaye, Stan, Banerji, Udai
Format: Online
Language:English
Published: Bentham Science Publishers 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531821/
id pubmed-3531821
recordtype oai_dc
spelling pubmed-35318212013-01-02 Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials Ang, Joo Ern Kaye, Stan Banerji, Udai Article Anti-cancer clinical drug development is currently costly and slow with a high attrition rate. There is thus an urgent and unmet need to integrate pharmacodynamic biomarkers into early phase clinical trials in the framework provided by the “pharmacologic audit trail” in order to overcome this challenge. This review discusses the rationale, advantages and disadvantages, as well as the practical considerations of various tissue-based approaches to perform pharmacodynamic studies in early phase oncology clinical trials using case histories of molecular targeting agents such as PI3K, m-TOR, HSP90, HDAC and PARP inhibitors. These approaches include the use of normal “surrogate” tissues such as peripheral blood mononuclear cells, platelet-rich plasma, plucked hair follicles, skin biopsies, plasma-based endocrine assays, proteomics, metabolomics and circulating endothelial cells. In addition, the review discusses the use of neoplastic tissues including tumor biopsies, circulating tumor DNA and tumor cells and metabolomic approaches. The utilization of these tissues and technology platforms to study biomarkers will help accelerate the development of molecularly targeted agents for the treatment of cancer. Bentham Science Publishers 2012-11 2012-11 /pmc/articles/PMC3531821/ /pubmed/22974395 http://dx.doi.org/10.2174/138945012803530062 Text en © 2012 Bentham Science Publishers http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ang, Joo Ern
Kaye, Stan
Banerji, Udai
spellingShingle Ang, Joo Ern
Kaye, Stan
Banerji, Udai
Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials
author_facet Ang, Joo Ern
Kaye, Stan
Banerji, Udai
author_sort Ang, Joo Ern
title Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials
title_short Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials
title_full Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials
title_fullStr Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials
title_full_unstemmed Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials
title_sort tissue-based approaches to study pharmacodynamic endpoints in early phase oncology clinical trials
description Anti-cancer clinical drug development is currently costly and slow with a high attrition rate. There is thus an urgent and unmet need to integrate pharmacodynamic biomarkers into early phase clinical trials in the framework provided by the “pharmacologic audit trail” in order to overcome this challenge. This review discusses the rationale, advantages and disadvantages, as well as the practical considerations of various tissue-based approaches to perform pharmacodynamic studies in early phase oncology clinical trials using case histories of molecular targeting agents such as PI3K, m-TOR, HSP90, HDAC and PARP inhibitors. These approaches include the use of normal “surrogate” tissues such as peripheral blood mononuclear cells, platelet-rich plasma, plucked hair follicles, skin biopsies, plasma-based endocrine assays, proteomics, metabolomics and circulating endothelial cells. In addition, the review discusses the use of neoplastic tissues including tumor biopsies, circulating tumor DNA and tumor cells and metabolomic approaches. The utilization of these tissues and technology platforms to study biomarkers will help accelerate the development of molecularly targeted agents for the treatment of cancer.
publisher Bentham Science Publishers
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531821/
_version_ 1611943225228001280

Similar Items