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Effect of AR antagonist combined with PARP1 inhibitor on sporadic triple-negative breast cancer bearing AR expression and methylation-mediated BRCA1 dysfunction

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机构: [1]Hebei Med Univ, Affiliated Hosp 4, Res Ctr & Tumor Res Inst, Shijiazhuang 050017, Hebei, Peoples R China [2]Hebei Med Univ, Affiliated Hosp 4, Breast Dis Diagnost & Therapeut Ctr, Shijiazhuang 050017, Hebei, Peoples R China [3]Hebei Univ Chinese Med, Dept Surg Nursing, Shijiazhuang 050200, Hebei, Peoples R China
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关键词: Triple-negative breast cancer Androgen receptor BRCA1 Enzalutamide Olaparib

摘要:
Triple-negative breast cancer (TNBC) patients usually present worse clinical outcomes due to their high heterogeneity. The purpose of our study is to investigate the prognostic role of AR and BRCA1 expression in sporadic TNBC patients, and effect of AR blockade and PARP1 inhibitor for TNBC patients who characterized by positive-AR expression and BRCA1 inactivation or dysfunction. In our present study, we found that AR is expressed in 43.6% and 34.0% of TNBC tissues, when 1% or 10% staining was used as the threshold for AR positivity, respectively. When 1% staining was used as the threshold, AR expression indicates a poor disease-free survival (DFS) of TNBC patients. TNBC patients with negative BRCA1 show a poor DFS, and BRCA1 suppression is associated with the methylation status of its promoter. Interestingly, BRCA1-/AR + TNBC patients have shorter DFS than other TNBC patients regardless of the threshold for AR positivity. AR antagonists MDV3100 enhances the PARP1 inhibitor Olaparib-mediated decrease of cell viability in AR-positive/BRCA1-inactivated cells in vitro and in vivo. Our results suggested that combination of AR blockade and PARP1 inhibitor may be a potential strategy for sporadic TNBC patients who characterized by positive-AR expression and BRCA1 inactivation or dysfunction.

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基金编号: 81001178 16967788D

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出版当年[2019]版:
大类 | 3 区 医学
小类 | 3 区 医学:研究与实验 3 区 药学
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验 2 区 药学
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出版当年[2019]版:
Q1 PHARMACOLOGY & PHARMACY Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2024]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 PHARMACOLOGY & PHARMACY

影响因子: 最新[2024版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [1]Hebei Med Univ, Affiliated Hosp 4, Res Ctr & Tumor Res Inst, Shijiazhuang 050017, Hebei, Peoples R China
通讯作者:
通讯机构: [1]Hebei Med Univ, Affiliated Hosp 4, Res Ctr & Tumor Res Inst, Shijiazhuang 050017, Hebei, Peoples R China [2]Hebei Med Univ, Affiliated Hosp 4, Breast Dis Diagnost & Therapeut Ctr, Shijiazhuang 050017, Hebei, Peoples R China [*1]Breast Disease Diagnostic and Therapeutic Center, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
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