TY - JOUR
T1 - New approaches to reverse resistance to hormonal therapy in human breast cancer
AU - Weinberg, Olga K.
AU - Marquez-Garban, Diana C.
AU - Pietras, Richard J.
N1 - Funding Information:
This work was supported by funds from the US Army Breast Cancer Research Program, the Stiles Program in Oncology, the Wells Fargo Foundation, the Hamburger Fund of the Jonsson Cancer Center Foundation and the Howard Hughes Medical Institute Fellowship Program.
PY - 2005/8
Y1 - 2005/8
N2 - Breast cancer is now the most common malignancy diagnosed in women. Growth factor and estrogen receptors elicit tight regulation of breast tumor progression. Estrogen receptors occur in about two-thirds of breast tumors, and endocrine therapy targeted to these receptors is effective in a large proportion of tumors that express both estrogen and progesterone receptors. However, after an initial period of response to hormonal therapy, such as tamoxifen, most tumors develop resistance leading to disease relapse. Emerging data suggest that previously unsuspected interactions between growth factor and estrogen signaling pathways contribute to growth promotion in breast cancer. Targeting different components of this signaling axis may allow development of more effective and less toxic antihormone treatments for breast cancer. In recent clinical studies, anastrozole, letrozole and exemestane, inhibitors of the estrogen synthase, aromatase, have shown advantages over tamoxifen as treatment for advanced disease. Fulvestrant is a new type of estrogen receptor antagonist that downregulates cellular levels of estrogen receptor and has no agonist activity. Due to its unique mode of action, fulvestrant may be an ideal candidate for combination treatment with inhibitors targeted to growth factor receptor signaling pathways. New understanding of estrogen receptor genes, gene transcripts and variants, post-translational modifications of receptor protein products and interactions with other signaling networks in tumor cells are leading us to unique targeted approaches in the hormonal therapy of breast cancer.
AB - Breast cancer is now the most common malignancy diagnosed in women. Growth factor and estrogen receptors elicit tight regulation of breast tumor progression. Estrogen receptors occur in about two-thirds of breast tumors, and endocrine therapy targeted to these receptors is effective in a large proportion of tumors that express both estrogen and progesterone receptors. However, after an initial period of response to hormonal therapy, such as tamoxifen, most tumors develop resistance leading to disease relapse. Emerging data suggest that previously unsuspected interactions between growth factor and estrogen signaling pathways contribute to growth promotion in breast cancer. Targeting different components of this signaling axis may allow development of more effective and less toxic antihormone treatments for breast cancer. In recent clinical studies, anastrozole, letrozole and exemestane, inhibitors of the estrogen synthase, aromatase, have shown advantages over tamoxifen as treatment for advanced disease. Fulvestrant is a new type of estrogen receptor antagonist that downregulates cellular levels of estrogen receptor and has no agonist activity. Due to its unique mode of action, fulvestrant may be an ideal candidate for combination treatment with inhibitors targeted to growth factor receptor signaling pathways. New understanding of estrogen receptor genes, gene transcripts and variants, post-translational modifications of receptor protein products and interactions with other signaling networks in tumor cells are leading us to unique targeted approaches in the hormonal therapy of breast cancer.
KW - Antiestrogen
KW - Aromatase inhibitor
KW - Breast cancer
KW - EGFR
KW - Estrogen receptor
KW - Growth factor receptor
KW - HER-2/neu
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U2 - 10.1016/j.drup.2005.06.002
DO - 10.1016/j.drup.2005.06.002
M3 - Article
C2 - 16054421
AN - SCOPUS:26844480683
SN - 1368-7646
VL - 8
SP - 219
EP - 233
JO - Drug Resistance Updates
JF - Drug Resistance Updates
IS - 4
ER -