Lasalle Claudia, Wang Yulu, Morales Maria T, Giubellino Alessio, Amber Kyle T, Mansini Adrian P
Department of Dermatology, Rush University Medical Center, Chicago, IL 60612, USA.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Cancers (Basel). 2025 Aug 29;17(17):2828. doi: 10.3390/cancers17172828.
Melanoma is one of the most aggressive skin cancers, with increasing rates of occurrence. Although it has not traditionally been considered hormonally driven, recent evidence links androgen receptor (AR) signaling to important aspects of melanoma biology, including tumor growth, metastasis, immune evasion, and resistance to therapy. Mechanistically, AR promotes melanoma progression by activating a pro-metastatic gene program, suppressing anti-tumor immune responses, and altering the tumor microenvironment. Additionally, emerging data indicate AR's involvement in resistance to chemotherapy and immune-based therapies. This review provides a comprehensive overview of AR's intricate role in melanoma, focusing on its molecular mechanisms, its impact on immune evasion and therapy resistance, and its potential clinical applications. We also assess AR-targeted strategies, including androgen deprivation therapy and AR antagonists, to improve the effectiveness of chemotherapy, targeted therapy, and immunotherapy. Understanding AR's role in melanoma could lead to new treatment options, particularly for sex-specific patient groups.
黑色素瘤是最具侵袭性的皮肤癌之一，发病率不断上升。尽管传统上并不认为它是由激素驱动的，但最近的证据将雄激素受体（AR）信号传导与黑色素瘤生物学的重要方面联系起来，包括肿瘤生长、转移、免疫逃逸和对治疗的耐药性。从机制上讲，AR通过激活促转移基因程序、抑制抗肿瘤免疫反应和改变肿瘤微环境来促进黑色素瘤进展。此外，新出现的数据表明AR参与了对化疗和免疫疗法的耐药性。本综述全面概述了AR在黑色素瘤中的复杂作用，重点关注其分子机制、对免疫逃逸和治疗耐药性的影响以及其潜在的临床应用。我们还评估了以AR为靶点的策略，包括雄激素剥夺疗法和AR拮抗剂，以提高化疗、靶向治疗和免疫治疗的有效性。了解AR在黑色素瘤中的作用可能会带来新的治疗选择，特别是针对特定性别的患者群体。
