TY - JOUR
T1 - Cross-resistance and molecular mechanisms in antiestrogen resistance
AU - Clarke, R.
AU - Brünner, N.
PY - 1995
Y1 - 1995
N2 - Almost all initially responsive breast tumors acquire resistance to the triphenylethylene antiestrogen tamoxifen (TAM). Development of resistance represents the major restriction in the current use of TAM. More recently, a series of steroidal antiestrogens have been developed (e.g. ICI 182,780), and we wished to determine whether cross-resistance among these drugs occurs, and what the likely mechanisms of resistance are. We have further selected breast cancer variant cell lines that no longer require estrogens for growth (MCF-7/LCC-1) against either 4-hydroxytamoxifen (MCF-7/LLC-2) or ICI 182,780 (MCF-7/LCC-9). Analysis of the resistance phenotypes suggests that TAM resistant cells can retain responsiveness to the steroidal antiestrogens, whereas cells selected against ICI 182,780 are cross-resistant to TAM. If similar resistance patterns are acquired in patients, a sequential modality with TAN as the first-line and ICI 182,780 as a second-line drug, is suggested. We have generated a gene-network hypothesis to explain these differential resistance patterns and outline their potential molecular mechanisms.
AB - Almost all initially responsive breast tumors acquire resistance to the triphenylethylene antiestrogen tamoxifen (TAM). Development of resistance represents the major restriction in the current use of TAM. More recently, a series of steroidal antiestrogens have been developed (e.g. ICI 182,780), and we wished to determine whether cross-resistance among these drugs occurs, and what the likely mechanisms of resistance are. We have further selected breast cancer variant cell lines that no longer require estrogens for growth (MCF-7/LCC-1) against either 4-hydroxytamoxifen (MCF-7/LLC-2) or ICI 182,780 (MCF-7/LCC-9). Analysis of the resistance phenotypes suggests that TAM resistant cells can retain responsiveness to the steroidal antiestrogens, whereas cells selected against ICI 182,780 are cross-resistant to TAM. If similar resistance patterns are acquired in patients, a sequential modality with TAN as the first-line and ICI 182,780 as a second-line drug, is suggested. We have generated a gene-network hypothesis to explain these differential resistance patterns and outline their potential molecular mechanisms.
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U2 - 10.1677/erc.0.0020059
DO - 10.1677/erc.0.0020059
M3 - Review article
AN - SCOPUS:0028919074
SN - 1351-0088
VL - 2
SP - 59
EP - 72
JO - Endocrine-related cancer
JF - Endocrine-related cancer
IS - 1
ER -