Hendrix Lauren N, Hamilton David A, Kyprianou Natasha
a Division of Urology, University of Kentucky College of Medicine, Lexington, KY, USA.
b Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA.
Expert Rev Endocrinol Metab. 2013 Jul;8(4):403-416. doi: 10.1586/17446651.2013.811914.
Advanced prostate cancer will claim nearly 30,000 lives among men in the USA in the year 2013. Most of these will be castration-resistant prostate cancers that are not responsive to traditional therapeutic modalities, and there is no available regimen that fully eradicates metastatic disease. This poses a significant clinical challenge for practitioners and has stimulated the development of novel agents that target these castration-resistant tumor cells. Development of metastatic prostate cancer is orchestrated by multiple signaling pathways that regulate cell survival, apoptosis, anoikis, epithelial-mesenchymal transition (EMT), invasion, the androgen signaling axis and angiogenesis. Disruption of the mechanisms underlying these processes is critical for development of agents that can target otherwise resistant tumor cells. Insights into the mechanisms by which rounds of EMT/mesenchymal-epithelial transition conversions facilitate the progression of localized prostate carcinomas to advanced metastatic and castration-resistant disease emerge as attractive targets for drug development. In this review, the authors discuss the current understanding of therapeutic resistance in castration-resistant prostate cancer with focus on the androgen receptor signaling axis and EMT. Novel therapeutic approaches targeting critical players of both pathways as well as the results from ongoing clinical trials will be discussed in this review.
2013年，美国将有近3万名男性死于晚期前列腺癌。其中大多数将是去势抵抗性前列腺癌，对传统治疗方式无反应，且目前尚无能够完全根除转移性疾病的治疗方案。这给临床医生带来了重大挑战，并促使人们研发针对这些去势抵抗性肿瘤细胞的新型药物。转移性前列腺癌的发展由多种信号通路调控，这些信号通路调节细胞存活、凋亡、失巢凋亡、上皮-间质转化（EMT）、侵袭、雄激素信号轴和血管生成。破坏这些过程背后的机制对于开发能够靶向原本耐药的肿瘤细胞的药物至关重要。对EMT/间质-上皮转化循环促进局限性前列腺癌发展为晚期转移性和去势抵抗性疾病的机制的深入了解，成为了有吸引力的药物开发靶点。在这篇综述中，作者讨论了目前对去势抵抗性前列腺癌治疗耐药性的理解，重点关注雄激素受体信号轴和EMT。本文还将讨论针对这两条通路关键参与者的新型治疗方法以及正在进行的临床试验结果。
