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Ariazi EA, Lewis-Wambi JS, Gill SD, Pyle JR, Ariazi JL, Kim HR, Sharma CG, Cordera F, Shupp HA, Li TY, Jordan VC
Emerging principles for the development of resistance to antihormonal therapy: Implications for the clinical utility of fulvestrant
Journal of Steroid Biochemistry and Molecular Biology (2006) 102:128-138.
Abstract
We seek to evaluate the clinical consequences of resistance to antihormonal therapy by studying analogous animal xenograft models. Two approaches were taken: (1) MCF-7 tumors were serially transplanted into selective estrogen receptor modulator (SERM)-treated immunocompromised mice to mimic 5 years of SERM treatment. The studies in vivo were designed to replicate the development of acquired resistance to SERMs over years of clinical exposure. (2) MCF-7 cells were cultured long-term under SERM-treated or estrogen withdrawn conditions (to mimic aromatase inhibitors), and then injected into mice to generate endocrine-resistant xenografts. These tumor models have allowed us to define Phase I and Phase II antihormonal resistance according to their responses to E-2 and fulvestrant. Phase I SERM-resistant tumors were growth stimulated in response to estradiol (E-2), but paradoxically, Phase II SERM and estrogen withdrawn-resistant tumors were growth inhibited by E-2. Fulvestrant!
Note
Publication Date: 2006-12-01.
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