Metabolizadores

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Cancer pharmacogenomics: do cancer cell lines have the right stuff?
“With the advent of next-generation sequencing technologies, we are at a tipping point where we can gain unprecedented insights into the genetic alterations present in different cancers.”
KEYWORDS: cancer n chemotherapy response n NCI60 panel npharmacogenetics n tumor cell line

In order to improve cancer patient outcomes, considerable effort has been undertaken to identify genomic alterations that impact patient response to chemotherapy. Once all the relevant alterations become known, it is hoped that the promise of individualized therapy, where each patient is treated with the optimal chemotherapy regimen for their tumor, would becomefulfilled. Since clinical tissues are limited both in quan­ tity and availability, many researchers have used cancer cell lines in their pharmacogenomics research. Cancer cell lines serve as useful models for clinical tumors because they proliferate read­ ily, are experimentally tractable and are a renew­ able resource. One such resource in pharmaco­ genomics research is the NCI60 panel, a panelof 60 different cell lines encompassing nine differ­ ent types of cancer (reviewed in [1]). The NCI60 panel has been utilized in studies to screen com­ pounds for cytotoxic activity and potential clini­ cal targets, while also identifying the necessary molecular factors required for cytotoxic activity. But with all the effort and money being put into pharmacogenomics research using cancer celllines, it is appropriate to ask: how faithfully do cancer cell lines represent the tumors that they are being used to model? First, do cancer cell lines look like the tumors they are modeling? The good news is that, in general, cancer cell lines look like their tis­ sue of origin at the molecular level (i.e., gene­ expression patterns and genomic alterations), at least when compared with cancer celllines derived from other tissues. Using a microarray­ based gene­expression profiling approach, Ross et al. were able to identify gene­expression pat­ terns in the NCI60 cancer cell line panel that corresponded to the tissue of origin from which the cell lines were derived [2] . However, not all cancer cell lines fully represent their tissues of
10.2217/PGS.10.107 © 2010 Future Medicine Ltdorigin. A study by Sandberg et al. comparing expression profiles of the NCI60 panel with their corresponding in vivo tumors indicated that only approximately 50% of the cancer cell lines tested were most similar to their tissue of origin [3] . In fact, the authors found that the cancer cell lines varied widely in their expression of tumor characteristic genes, which impacted the propri­ ety ofsome of the cell lines for the tissues they were supposed to be modeling. Some of the dif­ ferences in gene expression between cancer cell lines and their tissue of origin are probably due to the presence of contaminating stromal cells in in vivo tumors; however, there is some evidence that stromal cells contribute little to the pat­ terns of gene expression observed in tumors [4] . Overall, whilemany cancer cell lines fully repre­ sent their tissue of origin at the molecular level, care should be taken to determine the suitability of individual cancer cell lines for the research in question.

J Todd Auman
UNC Institute for Pharmacogenomics & Individualized Therapy, The University of North Carolina at Chapel Hill, UNC Eshelman School of Pharmacy, Room 1096, Genetic Medicine Building,Campus Box 7361, 120 Mason Farm Road, Chapel Hill, NC 27599-7361, USA Tel.: +1 919 966 6995 Fax: +1 919 966 5863 jtauman@email.unc.edu

“…cancer cell lines are likely to be poor choices for discovering novel genomic or epigenetic alterations that are relevant to cytotoxic drug response…”
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