Date of Award
Fall 8-22-2025
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Molecular Biology
First Advisor
Steven Kregel
Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related death in men. Early-stage PCa is treatable with androgen deprivation therapy (ADT) but resistance develops frequently, leading to castration-resistant PCa (CRPC). AR antagonists like enzalutamide are common therapies for CRPC, but late-stage disease is often fatal. Enzalutamide-resistant PCa exhibits high oxidative stress and upregulates antioxidant systems, notably the thioredoxin (Trx) system, which depends on ubiquitous thioredoxin reductases, TXNRD1 and TXNRD2. This cycle promotes survival by regulating transcription, proliferation, and apoptosis. TXNRD2 levels are higher in tumor tissue, suggesting patients may benefit from a TXNRD inhibitor. We identified a new class of non-covalent TXNRD inhibitors. siRNA knockdowns of TXNRD1 and TXNRD2 significantly reduced PCa cell viability. Two non-covalent inhibitors, 8VP101 and 9VP19, also decreased proliferation in vitro and synergized with enzalutamide to increase treatment efficacy. Ongoing studies aim to further characterize these compounds for potential therapeutic use in aggressive, late-stage PCa.
Recommended Citation
Deegan, Carleen Danielle, "The Role of Thioredoxin Reductase Paralogs in Prostate Cancer" (2025). Dissertations. 4270.
https://ecommons.luc.edu/luc_diss/4270
