Drug-eluting microarrays to identify effective chemotherapeutic combinations targeting patient-derived cancer stem cells

Matthew R. Carstens, Robert C. Fisher, Abhinav P. Acharya, Elizabeth A. Butterworth, Edward Scott, Emina H. Huang, Benjamin G. Keselowsky

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

A new paradigm in oncology establishes a spectrum of tumorigenic potential across the heterogeneous phenotypes within a tumor. The cancer stem cell hypothesis postulates that a minute fraction of cells within a tumor, termed cancer stem cells (CSCs), have a tumor-initiating capacity that propels tumor growth. An application of this discovery is to target this critical cell population using chemotherapy; however, the process of isolating these cells is arduous, and the rarity of CSCs makes it difficult to test potential drug candidates in a robust fashion, particularly for individual patients. To address the challenge of screening drug libraries on patient-derived populations of rare cells, such as CSCs, we have developed a drug-eluting microarray, a miniaturized platform onto which a minimal quantity of cells can adhere and be exposed to unique treatment conditions. Hundreds of drug-loaded polymer islands acting as drug depots colocalized with adherent cells are surrounded by a nonfouling background, creating isolated culture environments on a solid substrate. Significant results can be obtained by testing <6% of the cells required for a typical 96-well plate. Reliability was demonstrated by an average coefficient of variation of 14% between all of the microarrays and 13% between identical conditions within a single microarray. Using the drug-eluting array, colorectal CSCs isolated from two patients exhibited unique responses to drug combinations when cultured on the drug-eluting microarray, highlighting the potential as a prognostic tool to identify personalized chemotherapeutic regimens targeting CSCs.

Original languageEnglish (US)
Pages (from-to)8732-8737
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number28
DOIs
StatePublished - Jul 14 2015

Keywords

  • Cancer stem cell
  • Chemopredictive
  • Combination therapy
  • Microarray
  • Personalized medicine

ASJC Scopus subject areas

  • General

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