Brown Nicholas E, Sullivan Camille, Waltz Susan E
Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Research Service, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45267, USA.
EMS Cancer Sci J. 2018;1(1). Epub 2018 Jul 30.
The Ron receptor tyrosine kinase was initially discovered as a protein which played a critical role in regulating inflammatory responses. This effect was primarily determined through studies in various macrophage populations. Since its initial discovery, a role has emerged for Ron as a driver of cancer within epithelial cells. After numerous publications have detailed a role for Ron in promoting tumor initiation, growth, and metastasis, Ron has been designated as an emerging therapeutic option in a variety of cancers.
This review discusses the current literature regarding the role of Ron in prostate cancer and places special emphasis on the role of Ron in both epithelial cells and macrophages. Whole body loss of Ron signaling initially exposed a variety of prostate cancer growth mechanisms regulated by Ron. With the knowledge that Ron plays an integral part in regulating the function of epithelial cells and macrophages, studies commenced to discern the cell type specific functions for Ron in prostate cancer. A novel role for Ron in promoting Castration Resistant Prostate Cancer has recently been uncovered, and the results of these studies are summarized herein. Furthermore, this review gives a summary of several currently available compounds which show promise at targeting Ron in both epithelial and macrophage populations.
Sufficient evidence has been provided for the initiation of clinical trials focused on targeting Ron in both macrophage and epithelial compartments for the treatment of prostate cancer. A number of therapeutic avenues for targeting Ron in prostate cancer are currently available; however, special consideration will need to take place knowing that Ron signaling impacts multiple cell types. Further understanding of the cell type specific functions of Ron in prostate cancer will help inform and shape future clinical research and therapeutic strategies.
Ron受体酪氨酸激酶最初被发现是一种在调节炎症反应中起关键作用的蛋白质。这种作用主要是通过对各种巨噬细胞群体的研究确定的。自最初发现以来,Ron已成为上皮细胞内癌症驱动因子。在众多出版物详细阐述了Ron在促进肿瘤起始、生长和转移中的作用后,Ron已被指定为多种癌症中一种新兴的治疗选择。
本综述讨论了关于Ron在前列腺癌中作用的当前文献,并特别强调了Ron在上皮细胞和巨噬细胞中的作用。Ron信号通路的全身缺失最初揭示了多种受Ron调节的前列腺癌生长机制。鉴于Ron在调节上皮细胞和巨噬细胞功能中起着不可或缺的作用,研究开始辨别Ron在前列腺癌中的细胞类型特异性功能。最近发现了Ron在促进去势抵抗性前列腺癌中的新作用,本文总结了这些研究结果。此外,本综述总结了几种目前可用的化合物,它们有望在上皮细胞和巨噬细胞群体中靶向Ron。
已有充分证据表明应启动针对巨噬细胞和上皮细胞区室中Ron的临床试验,以治疗前列腺癌。目前有多种针对前列腺癌中Ron的治疗途径;然而,鉴于Ron信号通路会影响多种细胞类型,需要特别考虑。进一步了解Ron在前列腺癌中的细胞类型特异性功能将有助于为未来的临床研究和治疗策略提供信息并塑造这些策略。