Cell microarray platform for anticancer drug development

Min Jung Lee, Joo Chung Eun, Sunmin Lee, Joon Yong Chung, William G. Telford, Edward A. Sausville, Ivana Gojo, Judith E. Karp, Steven D. Gore, Veena Kapoor, Sang Kim Yeong, Shivaani Kummar, Martin Gutierrez, Stephen M. Hewitt, Jane B. Trepel

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)226-234
Number of pages9
JournalDrug Development Research
Volume68
Issue number5
DOIs
StatePublished - Aug 1 2007

Keywords

  • High-throughput
  • Histone deacetylase inhibitor
  • Pharmacodynamic
  • Tissue microarray

ASJC Scopus subject areas

  • Drug Discovery

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