Titration of Androgen Signaling: How Basic Studies Have Informed Clinical Trials Using High-Dose Testosterone Therapy in Castrate-Resistant Prostate Cancer.

ABSTRACT: Since the Nobel Prize-winning work of Huggins, androgen ablation has been a mainstay for treatment of recurrent prostate cancer. While initially effective for most patients, prostate cancers inevitably develop the ability to survive, grow, and metastasize further, despite ongoing androgen suppression. Here, we briefly review key preclinical studies over decades and include illustrative examples from our own laboratories that suggest prostate cancer cells titrate androgen signaling to optimize growth. Such laboratory-based studies argue that adaptations that allow growth in a low-androgen environment render prostate cancer sensitive to restoration of androgens, especially at supraphysiologic doses. Based on preclinical data as well as clinical observations, trials employing high-dose testos

SUBMITTER: Nordeen SK 

PROVIDER: S-EPMC8465783 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature