TY - JOUR
T1 - Predicting drug sensitivity and resistance
T2 - Profiling ABC transporter genes in cancer cells
AU - Szakács, Gergely
AU - Annereau, Jean Philippe
AU - Lababidi, Samir
AU - Shankavaram, Uma
AU - Arciello, Angela
AU - Bussey, Kimberly J.
AU - Reinhold, William
AU - Guo, Yanping
AU - Kruh, Gary D.
AU - Reimers, Mark
AU - Weinstein, John N.
AU - Gottesman, Michael M.
N1 - Funding Information:
We thank Balázs Sarkadi for the MDCKII cell lines. We thank the staff of NCI DTP for generation of the pharmacological database used in this study and George Leiman for editorial assistance. This work was supported by the National Institutes of Health.
PY - 2004/8
Y1 - 2004/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2004.06.026
DO - 10.1016/j.ccr.2004.06.026
M3 - Article
C2 - 15324696
AN - SCOPUS:5144226566
SN - 1535-6108
VL - 6
SP - 129
EP - 137
JO - Cancer cell
JF - Cancer cell
IS - 2
ER -