Predicting drug sensitivity and resistance

Profiling ABC transporter genes in cancer cells

G. 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

Research output: Contribution to journalArticle

388 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 2004

Fingerprint

ATP-Binding Cassette Transporters
Neoplasm Genes
Drug Resistance
National Cancer Institute (U.S.)
Multiple Drug Resistance
Artifacts
Real-Time Polymerase Chain Reaction
Neoplasms
Technology
Drug Therapy
Cell Line
Messenger RNA
Growth
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Szakács, G., Annereau, J. P., Lababidi, S., Shankavaram, U., Arciello, A., Bussey, K. J., ... 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

Predicting drug sensitivity and resistance : Profiling ABC transporter genes in cancer cells. / Szakács, G.; Annereau, Jean Philippe; Lababidi, Samir; Shankavaram, Uma; Arciello, Angela; Bussey, Kimberly J.; Reinhold, William; Guo, Yanping; Kruh, Gary D.; Reimers, Mark; Weinstein, John N.; Gottesman, Michael M.

In: Cancer Cell, Vol. 6, No. 2, 08.2004, p. 129-137.

Research output: Contribution to journalArticle

Szakács, G, Annereau, JP, Lababidi, S, Shankavaram, U, Arciello, A, Bussey, KJ, Reinhold, W, Guo, Y, Kruh, GD, Reimers, M, Weinstein, JN & Gottesman, MM 2004, 'Predicting drug sensitivity and resistance: Profiling ABC transporter genes in cancer cells', Cancer Cell, vol. 6, no. 2, pp. 129-137. https://doi.org/10.1016/j.ccr.2004.06.026
Szakács, G. ; Annereau, Jean Philippe ; Lababidi, Samir ; Shankavaram, Uma ; Arciello, Angela ; Bussey, Kimberly J. ; Reinhold, William ; Guo, Yanping ; Kruh, Gary D. ; Reimers, Mark ; Weinstein, John N. ; Gottesman, Michael M. / Predicting drug sensitivity and resistance : Profiling ABC transporter genes in cancer cells. In: Cancer Cell. 2004 ; Vol. 6, No. 2. pp. 129-137.
@article{8ec87fe4d59c4d2cb4f1f57497726059,
title = "Predicting drug sensitivity and resistance: Profiling ABC transporter genes in cancer cells",
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.",
author = "G. Szak{\'a}cs and Annereau, {Jean Philippe} and Samir Lababidi and Uma Shankavaram and Angela Arciello and Bussey, {Kimberly J.} and William Reinhold and Yanping Guo and Kruh, {Gary D.} and Mark Reimers and Weinstein, {John N.} and Gottesman, {Michael M.}",
year = "2004",
month = "8",
doi = "10.1016/j.ccr.2004.06.026",
language = "English",
volume = "6",
pages = "129--137",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Predicting drug sensitivity and resistance

T2 - Profiling ABC transporter genes in cancer cells

AU - Szakács, G.

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=5144226566&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=5144226566&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2004.06.026

DO - 10.1016/j.ccr.2004.06.026

M3 - Article

VL - 6

SP - 129

EP - 137

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 2

ER -