Castration-Resistant Prostate Cancer

P1/2, N=1200, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

In contrast to other coumarin-based inhibitors, osthole-derived compounds with extended C8-substitutions, interact with the SP1 pocket in a novel and distinct manner. These findings validate our design strategy of enhancing SP1 pocket binding to improve AKR1C3 selectivity over other AKR1C isoforms, and provide valuable structural insights for the further development of selective AKR1C3 inhibitors as potential therapeutics for CRPC.

P2, N=162, Active, not recruiting, Australian and New Zealand Urogenital and Prostate Cancer Trials Group | Trial completion date: Jan 2025 --> Dec 2026

P=N/A, N=100, Terminated, University Hospital, Montpellier | Trial completion date: Oct 2025 --> Jun 2026 | Recruiting --> Terminated; Flaw in the analytical technique

Sixteen-week-old mice underwent surgical and chemical castration (10 mg/Kg enzalutamide), alone or in combination with JPE (5.8 g/Kg)...Mechanistically, JPE-induced effects in castrated mice involved decrease of AR protein expression as well as ERβ beneficial actions, which included a putative stimulation of TGF-β tumor-suppressive actions. In conclusion, JPE prevented the progression of poorly differentiated tumors with CRPC traits in the TRAMP model by hampering EMT and modulating steroid hormone and TGF-β signaling.

The results indicate that NUSAP1 enhanced prostate cancer ENZ resistance through activation of the Wnt/β-Catenin-AR/AR-V7 signalling pathway. Targeting NUSAP1 could offer a potential therapeutic approach to address ENZ resistance in CRPC.

P=N/A, N=500, Active, not recruiting, Guangxi Medical University

P1, N=10, Recruiting, VitsGen Therapeutics Inc.

P1/2, N=0, Withdrawn, Novartis Pharmaceuticals | N=217 --> 0 | Not yet recruiting --> Withdrawn

P3, N=110, Active, not recruiting, AstraZeneca | Trial completion date: Apr 2026 --> Feb 2027

P1/2, N=10, Not yet recruiting, Queensland University of Technology

Treatment of metastatic, castration-resistant prostate cancer (mCRPC) remains clinically challenging due to tumor heterogeneity and resistance to standard microtubule-targeting agents, such as docetaxel and cabazitaxel. The top upregulated proteins, TTLL3, ANAPC7, PIK3CA, ARID4B, and COL16A1, are linked to microtubule dynamics and cell cycle regulation; the main downregulated, namely KDM2B, PTOV1, YWHAQ, PSMB6, and PRKCB, are involved in cell survival, protein homeostasis and mitotic checkpoint control. These findings provide proteomic evidence that (+)-PTC interferes with cytoskeletal protein dynamics and promotes apoptosis in mCRPC and so warranting its further investigation as a candidate anti-cancer scaffold.