文章：

非前列腺恶性肿瘤中的雄激素受体信号传导：挑战与机遇

Androgen receptor signalling in non-prostatic malignancies: challenges and opportunities

原文发布日期：2024-11-25

DOI: 10.1038/s41568-024-00772-w

类型: Review Article

开放获取: 否

英文摘要：

The androgen receptor (AR) signalling pathway has been intensively studied in the context of prostate cancer, where androgen deprivation therapy is part of the standard of care for metastatic disease. By contrast, fewer studies have investigated the impact and translational potential of targeting AR in other cancer types where it is also expressed and functional. In this Review, we discuss the current understanding of AR in non-prostatic cancer types and summarize ongoing AR-directed clinical trials. While different androgen levels contribute to sexual dimorphism in cancer, targeting the AR system could benefit both sexes and help overcome resistance to targeted therapies. However, a bimodal function of AR signalling, which suppresses stromal changes associated with the early stages of cancer development, also needs to be considered. Future research is necessary to scrutinize cellular and molecular mechanisms of action of AR in cancer cells and the tumour microenvironment, to develop selective modulators of AR activity, and to identify patients with non-prostatic cancer who might benefit from targeting this pathway. AR-directed manipulation of host immune cells may offer a promising therapeutic approach for many types of cancers.

摘要翻译： 

雄激素受体（AR）信号通路在前列腺癌研究中已得到深入探索，其中雄激素剥夺疗法是转移性疾病标准治疗方案的一部分。相比之下，针对其他同样表达且具有功能性AR的癌症类型，相关研究及其靶向治疗的转化潜力探索仍较匮乏。本综述讨论了目前对非前列腺癌中AR作用的理解，并总结了正在进行的AR靶向临床试验。虽然不同雄激素水平会导致癌症发生的性别差异，但靶向AR系统可能使不同性别患者均获益，并有助于克服靶向治疗耐药性。然而，AR信号具有双重作用：它既能抑制与癌症早期发展阶段相关的基质改变，这一功能也需纳入考量。未来研究需深入剖析AR在癌细胞及肿瘤微环境中的细胞与分子作用机制，开发AR选择性调节剂，并筛选可能从该通路靶向治疗中获益的非前列腺癌患者。针对宿主免疫细胞的AR定向调控可能为多种癌症类型提供具有前景的治疗策略。

原文链接：

Androgen receptor signalling in non-prostatic malignancies: challenges and opportunities