Prostate cancer remains one of the most commonly diagnosed cancers and a leading cause of cancer death in men. Initially, prostate tumors respond to hormonal therapies, but androgen-independent tumors refractory to these therapies emerge. Identifying the mechanisms responsible for the emergence of androgen independence has been the subject of multiple studies. This article reviews the multiple pathways that have been shown to promote androgen independence, including a recently described mechanism that involves androgen receptor proteolysis to a constitutively active ligand-independent isoform. Identifying the underlying mechanisms of androgen independence is crucial in the design of appropriate therapies for hormonally refractive neoplasms.
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