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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.