Biological Sciences Department, The University of Texas at Dallas, 800 West Campbell Road, FO31, Richardson, TX 75080, United States of America.
Biological Sciences Department, The University of Texas at Dallas, 800 West Campbell Road, FO31, Richardson, TX 75080, United States of America.
Pharmacol Ther. 2020 Jul;211:107538. doi: 10.1016/j.pharmthera.2020.107538. Epub 2020 Mar 19.
Prostate Cancer (PCa) is the second leading cause of cancer-related death in men. Adenocarcinoma of the prostate is primarily composed of Androgen Receptor-positive (AR) luminal cells that require AR transcriptional activity for survival and proliferation. As a consequence, androgen deprivation and anti-androgens are used to treat PCa patients whose disease progresses following attempted surgical or radiation interventions. Unfortunately, patients with advanced PCa can develop incurable castration-resistant PCa (CRPCa) due to mutated, variant, or overexpressed AR. Conversely, low or no AR accumulation or activity can also underlie castration resistance. Whether CRPCa is due to aberrant AR activity or AR independence, NF-κB signaling is also implicated in the initiation and maintenance of CRPCa and, thus, the NF-κB pathway may be a promising alternative therapeutic target. In this review, we present evidence that NF-κB signaling promotes CRPCa initiation and progression, describe the dichotomic role of NF-κB in the regulation of AR expression and activity and outline studies that explore NF-κB inhibitors as PCa therapies.
前列腺癌（PCa）是男性癌症相关死亡的第二大主要原因。前列腺腺癌主要由雄激素受体阳性（AR）腔细胞组成，这些细胞的存活和增殖需要 AR 转录活性。因此，雄激素剥夺和抗雄激素被用于治疗那些在尝试手术或放射干预后疾病进展的 PCa 患者。不幸的是，由于 AR 的突变、变体或过表达，患有晚期 PCa 的患者可能会发展为无法治愈的去势抵抗性 PCa（CRPCa）。相反，低水平或无 AR 积累或活性也可能导致去势抵抗。无论 CRPCa 是由于异常的 AR 活性还是 AR 独立性，NF-κB 信号通路都与 CRPCa 的发生和维持有关，因此，NF-κB 通路可能是一种有前途的替代治疗靶点。在这篇综述中，我们提出了证据表明 NF-κB 信号通路促进了 CRPCa 的发生和进展，描述了 NF-κB 在 AR 表达和活性调节中的双重作用，并概述了探索 NF-κB 抑制剂作为 PCa 治疗方法的研究。
