Coulter Jonathan B, Song Daniel Y, DeWeese Theodore L, Yegnasubramanian Srinivasan
The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD; Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.
Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.
Semin Radiat Oncol. 2022 Jan;32(1):76-81. doi: 10.1016/j.semradonc.2021.09.003.
Androgen receptor signaling blockade is perhaps the first example of targeted therapy in the treatment of cancer. Since the initial observations that prostate cancers depend on hormone signaling, hormonal therapies remain a cornerstone in the treatment of metastatic prostate cancer. Androgen deprivation therapy has been shown to improve outcomes involving treatment of prostate cancers with radiotherapy, though a mechanistic understanding into the optimal sequencing of androgen deprivation therapy and radiotherapy remains incomplete. In this review we highlight key clinical trials designed to study combinations of hormonal and radiotherapies and introduce recent discoveries into the complex biology of androgen receptor signaling and DNA damage and repair. These emerging mechanistic and translational studies may have profound implications on both our understanding of hormonal therapy and radiotherapy combinations and the development of novel treatment strategies for locally-advanced and metastatic castrate resistant prostate cancer.
雄激素受体信号通路阻断可能是癌症治疗中靶向治疗的首个范例。自最初观察到前列腺癌依赖激素信号以来，激素疗法一直是转移性前列腺癌治疗的基石。雄激素剥夺疗法已被证明可改善前列腺癌放疗的治疗效果，不过对于雄激素剥夺疗法与放疗的最佳联合顺序，其机制理解仍不完整。在本综述中，我们重点介绍了旨在研究激素疗法与放疗联合应用的关键临床试验，并介绍了雄激素受体信号通路以及DNA损伤与修复复杂生物学的最新发现。这些新出现的机制和转化研究可能对我们理解激素疗法与放疗联合应用以及开发局部晚期和转移性去势抵抗性前列腺癌的新治疗策略产生深远影响。
