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Pharmaceuticals 2016, 9(2), 33; doi:10.3390/ph9020033

Tumor Heterogeneity, Single-Cell Sequencing, and Drug Resistance

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany
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Academic Editor: Jean Jacques Vanden Eynde
Received: 28 December 2015 / Revised: 13 June 2016 / Accepted: 14 June 2016 / Published: 16 June 2016
(This article belongs to the Collection Choices of the Journal)
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Abstract

Tumor heterogeneity has been compared with Darwinian evolution and survival of the fittest. The evolutionary ecosystem of tumors consisting of heterogeneous tumor cell populations represents a considerable challenge to tumor therapy, since all genetically and phenotypically different subpopulations have to be efficiently killed by therapy. Otherwise, even small surviving subpopulations may cause repopulation and refractory tumors. Single-cell sequencing allows for a better understanding of the genomic principles of tumor heterogeneity and represents the basis for more successful tumor treatments. The isolation and sequencing of single tumor cells still represents a considerable technical challenge and consists of three major steps: (1) single cell isolation (e.g., by laser-capture microdissection), fluorescence-activated cell sorting, micromanipulation, whole genome amplification (e.g., with the help of Phi29 DNA polymerase), and transcriptome-wide next generation sequencing technologies (e.g., 454 pyrosequencing, Illumina sequencing, and other systems). Data demonstrating the feasibility of single-cell sequencing for monitoring the emergence of drug-resistant cell clones in patient samples are discussed herein. It is envisioned that single-cell sequencing will be a valuable asset to assist the design of regimens for personalized tumor therapies based on tumor subpopulation-specific genetic alterations in individual patients. View Full-Text
Keywords: intratumoral heterogeneity; tumor ecosystems; single-cell sequencing; micromanipulation; laser-capture microdissection; flow cytometry; next generation sequencing; RNA sequencing; whole genome amplification; multi-region sequencing; circulating tumor cells; xenograft tumor models; cancer treatment; individualized therapy; precision medicine intratumoral heterogeneity; tumor ecosystems; single-cell sequencing; micromanipulation; laser-capture microdissection; flow cytometry; next generation sequencing; RNA sequencing; whole genome amplification; multi-region sequencing; circulating tumor cells; xenograft tumor models; cancer treatment; individualized therapy; precision medicine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Schmidt, F.; Efferth, T. Tumor Heterogeneity, Single-Cell Sequencing, and Drug Resistance. Pharmaceuticals 2016, 9, 33.

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