TY - JOUR
T1 - Models and mechanisms of acquired antihormone resistance in breast cancer
T2 - Significant clinical progress despite limitations
AU - Sweeney, Elizabeth E.
AU - McDaniel, Russell E.
AU - Maximov, Philipp Y.
AU - Fan, Ping
AU - Craig Jordan, V.
PY - 2012
Y1 - 2012
N2 - Translational research for the treatment and prevention of breast cancer depends upon the four Ms: models, molecules, and mechanisms in order to create medicines. The process, to target the estrogen receptor (ER) in estrogen-dependent breast cancer, has yielded signifi cant advances in patient survivorship and the first approved medicines (tamoxifen and raloxifene) to reduce the incidence of any cancer in high- or low-risk women. This review focuses on the critical role of the few ER-positive cell lines (MCF-7, T47D, BT474, ZR-75-1) that continue to advance our understanding of the estrogenregulated biology of breast cancer. More importantly, the model cell lines have provided an opportunity to document the development and evolution of acquired antihormone resistance. The description of this evolutionary process that occurs in micrometastatic disease during up to a decade of adjuvant therapy would not be possible in the patient. The use of the MCF-7 breast cancer cell line, in particular, has been instrumental in discovering a vulnerability of ER-positive breast cancer exhaustively treated with antihormone therapy. Physiologic estradiol acts as an apoptotic trigger to cause tumor regression. These unanticipated fi ndings in the laboratory have translated to clinical advances in our knowledge of the paradoxical role of estrogen in the life and death of breast cancer.
AB - Translational research for the treatment and prevention of breast cancer depends upon the four Ms: models, molecules, and mechanisms in order to create medicines. The process, to target the estrogen receptor (ER) in estrogen-dependent breast cancer, has yielded signifi cant advances in patient survivorship and the first approved medicines (tamoxifen and raloxifene) to reduce the incidence of any cancer in high- or low-risk women. This review focuses on the critical role of the few ER-positive cell lines (MCF-7, T47D, BT474, ZR-75-1) that continue to advance our understanding of the estrogenregulated biology of breast cancer. More importantly, the model cell lines have provided an opportunity to document the development and evolution of acquired antihormone resistance. The description of this evolutionary process that occurs in micrometastatic disease during up to a decade of adjuvant therapy would not be possible in the patient. The use of the MCF-7 breast cancer cell line, in particular, has been instrumental in discovering a vulnerability of ER-positive breast cancer exhaustively treated with antihormone therapy. Physiologic estradiol acts as an apoptotic trigger to cause tumor regression. These unanticipated fi ndings in the laboratory have translated to clinical advances in our knowledge of the paradoxical role of estrogen in the life and death of breast cancer.
KW - antihormone
KW - breast cancer
KW - resistance
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U2 - 10.1515/hmbci-2011-0004
DO - 10.1515/hmbci-2011-0004
M3 - Article
C2 - 23308083
AN - SCOPUS:84880263301
SN - 1868-1883
VL - 9
SP - 143
EP - 163
JO - Hormone Molecular Biology and Clinical Investigation
JF - Hormone Molecular Biology and Clinical Investigation
IS - 2
ER -