Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Endocr Relat Cancer. 2019 Apr 1;26(4):R195-R209. doi: 10.1530/ERC-19-0009.
Currently, prostate cancer (PCa) remains the most commonly diagnosed solid tumor and the second leading cause of cancer-related deaths in US men. Most of these deaths are attributed to the development of castration-resistant (CR) PCa. ErbB-2 and ErbB family members have been demonstrated to contribute to the progression of this lethal disease. In this review, we focus on updating the role of ErbB-2 in advanced PCa progression and its regulation, including its regulation via ligand activation, miRNAs and protein phosphorylation. We also discuss its downstream signaling pathways, including AKT, ERK1/2 and STATs, involved in advanced PCa progression. Additionally, we evaluate the potential of ErbB-2, focusing on its protein hyper-phosphorylation status, as a biomarker for aggressive PCa as well as the effectiveness of ErbB-2 as a target for the treatment of CR PCa via a multitude of approaches, including orally available inhibitors, intratumoral expression of cPAcP, vaccination and immunotherapy.
目前，前列腺癌（PCa）仍然是美国男性中最常见的实体肿瘤和癌症相关死亡的第二大主要原因。这些死亡大多归因于去势抵抗性（CR）PCa 的发展。已经证明 ErbB-2 和 ErbB 家族成员有助于这种致命疾病的进展。在这篇综述中，我们重点关注 ErbB-2 在晚期 PCa 进展及其调控中的作用，包括通过配体激活、miRNAs 和蛋白质磷酸化进行调控。我们还讨论了其下游信号通路，包括 AKT、ERK1/2 和 STATs，它们参与了晚期 PCa 的进展。此外，我们评估了 ErbB-2 的潜力，重点关注其蛋白质过度磷酸化状态，作为侵袭性 PCa 的生物标志物，以及通过多种方法，包括口服抑制剂、肿瘤内表达 cPAcP、疫苗接种和免疫疗法，将 ErbB-2 作为治疗 CR PCa 的靶点的有效性。
