Androgen receptor gene mutation, rearrangement, polymorphism.
Androgen receptor gene mutation, rearrangement, polymorphism.
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DOI：
10.3978/j.issn.2223-4683.2013.09.15
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发表时间：
2013-09-01
影响因子：
2
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Eisermann K;Wang D;Jing Y;Pascal LE;Wang Z
由突变、重排和多态引起的雄激素受体(AR)的遗传异常导致了与野生型AR相比具有不同功能的突变受体。到目前为止，已有1000多个突变在AR中被报道，其中大多数与雄激素不敏感综合征(AIS)有关。虽然与前列腺癌相关的AR突变在早期局部疾病中较少发生，但在接受抗雄激素治疗的去势抵抗型前列腺癌(CRPC)患者中发生突变的频率更高，其中10%-30%的患者存在某种形式的AR突变。抗雄激素治疗的耐药性通常是由于LBD的功能获得突变所致，例如比卡鲁胺和最近的苯扎鲁胺(MDV3100)。因此，研究这些新的AR突变是由抗雄激素和其他小分子药理学药物耐药引起的。
Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents.