Androgen Receptor in Hormone Receptor-Positive Breast Cancer.
Androgen Receptor in Hormone Receptor-Positive Breast Cancer.
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激素受体阳性乳腺癌中的雄激素受体。
DOI：
10.3390/ijms25010476
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发表时间：
2023-12-29
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
激素受体亚型(HR+BCA)乳腺癌预后良好，对一线内分泌治疗(ET)有效。然而，大多数HR+BCA患者表现出内源性或获得性ET抵抗(ET-R)，并迅速发生不可治愈的转移性BCA。随着常规ET的失败，对于ET-R HR+BCA患者存在有限的靶向治疗。在HR阴性的BCA亚型中，雄激素受体(AR)正在成为一个有吸引力的替代治疗靶点。AR推动Lumina AR(LAR)三重阴性乳腺癌的进展，在临床试验中，LAR患者使用AR拮抗剂始终显示出积极的临床益处。相比之下，AR在HR+BCA中的作用更具矛盾性。HR+BCA的AR与良好的预后相关，但AR支持ET-R BCA的发展。虽然AR拮抗剂无效，但正在进行的选择性AR调节剂的临床试验已经显示出对HR+BCA患者的希望。为了了解AR在HR+BCA中的不协调作用，本文讨论了AR的结构和翻译后修饰对AR功能的影响。此外，还介绍了FDA批准的针对BCA的AR靶向药物的已完成和正在进行的临床试验。最后，我们确定了未来HR+BCA治疗的有前景的研究小分子和嵌合体药物。
Breast cancer subtypes expressing hormone receptors (HR+ BCa) have a good prognosis and respond to first-line endocrine therapy (ET). However, the majority of HR+ BCa patients exhibit intrinsic or acquired ET resistance (ET-R) and rapid onset of incurable metastatic BCa. With the failure of conventional ET, limited targeted therapy exists for ET-R HR+ BCa patients. The androgen receptor (AR) in HR-negative BCa subtypes is emerging as an attractive alternative target for therapy. The AR drives Luminal AR (LAR) triple-negative breast cancer progression, and LAR patients consistently exhibit positive clinical benefits with AR antagonists in clinical trials. In contrast, the function of the AR in HR+ BCa is more conflicting. AR in HR+ BCa correlates with a favorable prognosis, and yet, the AR supports the development of ET-R BCa. While AR antagonists were ineffective, ongoing clinical trials with a selective AR modulator have shown promise for HR+ BCa patients. To understand the incongruent actions of ARs in HR+ BCa, the current review discusses how the structure and post-translational modification impact AR function. Additionally, completed and ongoing clinical trials with FDA-approved AR-targeting agents for BCa are presented. Finally, we identify promising investigational small molecules and chimera drugs for future HR+ BCa therapy.
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