Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania,19107.
The Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Cold Spring Harb Perspect Med. 2019 Jan 2;9(1):a030486. doi: 10.1101/cshperspect.a030486.
Prostatic adenocarcinoma (PCa) remains a significant health concern. Although localized PCa can be effectively treated, disseminated disease remains uniformly fatal. PCa is reliant on androgen receptor (AR); as such, first-line therapy for metastatic PCa entails suppression of AR signaling. Although initially effective, recurrent tumors reactivate AR function, leading to a lethal stage of disease termed castration-resistant PCa (CRPC). Recent findings implicate AR signaling in control of DNA repair and show that alterations in DNA damage repair pathways are strongly associated with disease progression and poor outcome. This review will address the DNA repair alterations observed in the clinical setting, explore the anticipated molecular and cellular consequence of DNA repair dysfunction, and consider clinical strategies for targeting tumors with altered DNA repair.
前列腺腺癌（PCa）仍然是一个重大的健康问题。尽管局限性 PCa 可以得到有效治疗，但转移性疾病仍然是致命的。PCa 依赖雄激素受体（AR）；因此，转移性 PCa 的一线治疗需要抑制 AR 信号。尽管最初有效，但复发性肿瘤会重新激活 AR 功能，导致一种称为去势抵抗性 PCa（CRPC）的致命疾病阶段。最近的研究结果表明，AR 信号在控制 DNA 修复中起作用，并表明 DNA 损伤修复途径的改变与疾病进展和不良预后密切相关。这篇综述将讨论在临床环境中观察到的 DNA 修复改变，探讨 DNA 修复功能障碍的预期分子和细胞后果，并考虑针对具有改变的 DNA 修复的肿瘤的临床策略。
