Predicting drug sensitivity and resistance: Profiling ABC transporter genes in cancer cells

Gergely Szakács, Jean Philippe Annereau, Samir Lababidi, Uma Shankavaram, Angela Arciello, Kimberly J. Bussey, William Reinhold, Yanping Guo, Gary D. Kruh, Mark Reimers, John N. Weinstein, Michael M. Gottesman

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406 Citations (Scopus)

Abstract

For analysis of multidrug resistance, a major barrier to effective cancer chemotherapy, we profiled mRNA expression of the 48 known human ABC transporters in 60 diverse cancer cell lines (the NCI-60) used by the National Cancer Institute to screen for anticancer activity. The use of real-time RT-PCR avoided artifacts commonly encountered with microarray technologies. By correlating the results with the growth inhibitory profiles of 1,429 candidate anticancer drugs tested against the cells, we identified which transporters are more likely than others to confer resistance to which agents. Unexpectedly, we also found and validated compounds whose activity is potentiated, rather than antagonized, by the MDR1 multidrug transporter. Such compounds may serve as leads for development.

Original languageEnglish
Pages (from-to)129-137
Number of pages9
JournalCancer Cell
Volume6
Issue number2
DOIs
Publication statusPublished - Aug 1 2004

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ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Szakács, G., Annereau, J. P., Lababidi, S., Shankavaram, U., Arciello, A., Bussey, K. J., Reinhold, W., Guo, Y., Kruh, G. D., Reimers, M., Weinstein, J. N., & Gottesman, M. M. (2004). Predicting drug sensitivity and resistance: Profiling ABC transporter genes in cancer cells. Cancer Cell, 6(2), 129-137. https://doi.org/10.1016/j.ccr.2004.06.026