Strand Douglas W, Costa Daniel N, Francis Franto, Ricke William A, Roehrborn Claus G
Department of Urology, University of Texas Southwestern Medical Center, USA.
Department of Radiology, University of Texas Southwestern Medical Center, USA.
Differentiation. 2017 Jul-Aug;96:49-61. doi: 10.1016/j.diff.2017.07.005. Epub 2017 Aug 4.
Benign prostatic hyperplasia and associated lower urinary tract symptoms remain difficult to treat medically, resulting in hundreds of thousands of surgeries performed annually in elderly males. New therapies have not improved clinical outcomes since alpha blockers and 5 alpha reductase inhibitors were introduced in the 1990s. An underappreciated confounder to identifying novel targets is pathological heterogeneity. Individual patients display unique phenotypes, composed of distinct cell types. We have yet to develop a cellular or molecular understanding of these unique phenotypes, which has led to failure in developing targeted therapies for personalized medicine. This review covers the strategic experimental approach to unraveling the cellular pathogenesis of discrete BPH phenotypes and discusses how to incorporate these findings into the clinic to improve outcomes.
良性前列腺增生及相关下尿路症状在药物治疗上仍然困难重重,导致老年男性每年要进行数十万例手术。自20世纪90年代引入α受体阻滞剂和5α还原酶抑制剂以来,新疗法并未改善临床疗效。识别新靶点时一个未得到充分重视的混杂因素是病理异质性。个体患者表现出由不同细胞类型组成的独特表型。我们尚未从细胞或分子层面理解这些独特表型,这导致在开发个性化医疗的靶向治疗方面遭遇失败。本综述涵盖了解开离散型良性前列腺增生表型细胞发病机制的战略实验方法,并讨论了如何将这些发现应用于临床以改善治疗效果。