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Cell microarray platform for anticancer drug development
Author(s) -
Lee MinJung,
Chung Eun Joo,
Lee Sunmin,
Chung JoonYong,
Telford William G.,
Sausville Edward A.,
Gojo Ivana,
Karp Judith E.,
Gore Steven D.,
Kapoor Veena,
Kim Yeong Sang,
Kummar Shivaani,
Gutierrez Martin,
Hewitt Stephen M.,
Trepel Jane B.
Publication year - 2007
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20183
Subject(s) - peripheral blood mononuclear cell , medicine , bone marrow , histone deacetylase inhibitor , in vivo , histone deacetylase , clinical trial , tissue microarray , pharmacology , microarray , cancer research , pharmacodynamics , drug , immunology , oncology , pathology , in vitro , biology , pharmacokinetics , histone , immunohistochemistry , gene expression , biochemistry , microbiology and biotechnology , gene
Pharmacodynamic assessment of whether a drug has interacted with and modified its target is an essential component of molecularly targeted clinical trials. Although many trials are written with the intent to assess tumor biopsies, if available, thus far the great majority of early drug trials have used peripheral blood mononuclear cells (PBMC) as a tumor surrogate. Typically, PBMC are studied by low‐throughput techniques such as Western blot. We present the use of a cell‐based tissue microarray for assessment of anticancer drug activity in vivo. We demonstrate the utility of this technique for analysis of protein hyperacetylation in response to treatment with the histone deacetylase inhibitor, SNDX‐275 in PBMC treated in vitro and in PBMC and bone marrow aspirates from patients in Phase I clinical trials with SNDX‐275. We demonstrate that the cell microarray can be used to measure drug response in a high‐throughput manner, allowing analysis of an entire trial on one or two glass slides. The cell microarray technique brings the advantages of the tissue microarray platform to the pharmacodynamic assessment of single cells, such as those isolated from bone marrow aspirates, fine needle aspirates, or malignant effusions, and to analysis of PBMC, the most commonly studied surrogate in oncology trials. Drug Dev Res 68:226–234, 2007. Published 2007 Wiley‐Liss, Inc.