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.
Szakács
Gergely
G
Laboratory of Cell Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD, 20892, USA. szakacsg@mail.nih.gov
Annereau
Jean-Philippe
JP
Lababidi
Samir
S
Shankavaram
Uma
U
Arciello
Angela
A
Bussey
Kimberly J
KJ
Reinhold
William
W
Guo
Yanping
Y
Kruh
Gary D
GD
Reimers
Mark
M
Weinstein
John N
JN
Gottesman
Michael M
MM
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