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

Cancer Cell. 2004 Aug;6(2):129-37. doi: 10.1016/j.ccr.2004.06.026.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Cell Line, Tumor
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Drug Screening Assays, Antitumor
  • Gene Expression Profiling*
  • Humans
  • Neoplasms / genetics*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Statistics as Topic

Substances

  • ATP-Binding Cassette Transporters
  • RNA, Messenger