The Cardiotoxic Effects of Androgen Deprivation Therapy in Men Treated for Prostate Cancer

Background: Prostate cancer (PC) is the second leading cause of cancer-associated mortality among men. In addition, cardiovascular disease (CVD) is the most common cause of death in men with PC who survive chemotherapy. Although androgen deprivation therapy (ADT) has significantly improved cancer survival rates, the incidence of CVD has subsequently increased. Non-Hispanic black (NHB) men with PC tend to experience more severe CVD compared to non-Hispanic white (NHW) men with PC for reasons unknown. Transforming growth factors (TGFs) and cyclin-dependent kinases (CDKs) are two different families of genes that contribute to CVD (i.e., cardiotoxicity). Thus, this study sought to investigate the effects of ADT on various proteins related to cardiotoxicity in men with PC. Methods: Nineteen men (8 NHB, 11 NHW) with a new clinical diagnosis of PC were enrolled in this study. Blood samples were collected at baseline and 4 weeks and 12 weeks following initiation of ADT. O-link proteomics was performed at all time points to determine genes related to cardiotoxicity, which are presented as normalized units. Results: Elevated expression among some members of the TGF and CDK families was observed following ADT. Specifically, an increase ( p =0.083) in the expression of TGF-Beta Activated Kinase 1 (TAB2) was observed from baseline to 12 weeks in both NHB and NHW men with PC. However, there appears to be a greater difference in the change (p=0.321 in TAB2 expression in the NHB (4.0±0.7 to 4.4±0.4) men when compared to NHW men (4.2±0.6 to 4.9±0.3). In addition, Menage A Trois 1 (MNAT), a CDK-Activating kinase assembly factor, increased (p=0.082) from baseline (0.4±1.1) to 4 weeks (1.1±0.9). Conclusion: Findings from the present investigation indicate that TGFs and CDKs, genes that contribute to CVD, were not only upregulated following ADT in men with PC, but race may also play a role in the cardiotoxicity gene expression. Therapies designed to regulate CDK and TGF isoforms represent a novel approach to decrease the CVD risk associated with ADT in men with prostate cancer; however, future studies are certainly warranted. AHA Strategically Focused Research Network: SFRN 863621 (RAH, AG, NLW) Laboratory of Integrative Vascular and Exercise Physiology (LIVEP) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.