Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells.
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.
Laboratory of Cell Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD, 20892, USA. szakacsg@mail.nih.gov
Gergely
G
Szakács
Jean-Philippe
JP
Annereau
Samir
S
Lababidi
Uma
U
Shankavaram
Angela
A
Arciello
Kimberly J
KJ
Bussey
William
W
Reinhold
Yanping
Y
Guo
Gary D
GD
Kruh
Mark
M
Reimers
John N
JN
Weinstein
Michael M
MM
Gottesman
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D020869:Gene Expression Profiling; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D013223:Statistics as Topic
D018528:ATP-Binding Cassette Transporters; D012333:RNA, Messenger