Stimulating Soluble Guanylyl Cyclase with the Clinical Agonist Riociguat Restrains the Development and Progression of Castration-Resistant Prostate Cancer.

ABSTRACT: Castration-resistant prostate cancer (CRPC) is incurable and fatal, making prostate cancer the second leading cancer-related cause of death for American men. CRPC results from therapeutic resistance to standard-of-care androgen deprivation (AD) treatments, through incompletely understood molecular mechanisms, and lacks durable therapeutic options. In this study, we identified enhanced soluble guanylyl cyclase (sGC) signaling as a mechanism that restrains CRPC initiation and growth. Patients with aggressive, fatal CRPC exhibited significantly lower serum levels of the sGC catalytic product cyclic GMP (cGMP) compared with the castration-sensitive stage. In emergent castration-resistant cells isolated from castration-sensitive prostate cancer populations, the obligate sGC heterodimer was repr

SUBMITTER: Zhang L 

PROVIDER: S-EPMC11695179 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature