Drug-eluting microarrays to identify effective chemotherapeutic combinations targeting patient-derived cancer stem cells
Drug-eluting microarrays to identify effective chemotherapeutic combinations targeting patient-derived cancer stem cells
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DOI:
10.1073/pnas.1505374112
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发表时间:
2015-07-14
影响因子:
11.1
通讯作者:
Keselowsky, Benjamin G.
中科院分区:
文献类型:
--
作者:
Carstens, Matthew R.;Fisher, Robert C.;Keselowsky, Benjamin G.
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