Castration-Resistant Prostate Cancer

P2, N=154, Active, not recruiting, MacroGenics | Trial completion date: Sep 2027 --> Mar 2026 | Trial primary completion date: Sep 2026 --> Feb 2026

P2, N=87, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P2, N=7, Terminated, M.D. Anderson Cancer Center | Trial completion date: Apr 2027 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Apr 2027 --> Mar 2026; <75% participation

The aberrant expression/activation of DAG-regulated kinases during prostate cancer progression results in pronounced deregulation and rewiring of transcriptional networks associated with cell cycle control, invasiveness, and cancer cell interactions with the tumor microenvironment (TME). The multifaceted regulation of nuclear functions by these pleiotropic kinases underscores their convoluted roles in prostate cancer development and progression, offering new opportunities for therapeutic targeting.

P3, N=138, Recruiting, Janssen Research & Development, LLC | N=63 --> 138

Pharmacological inhibition of STAT3, stabilization of tetrameric PKM2 by L-serine, and ROS scavenging with N-acetylcysteine significantly reduced STAT3 phosphorylation, PKM2 nuclear translocation, and HIF-1α stabilization...Functionally, treated cells exhibited reduced Ki-67 expression and impaired clonogenic capacity. Our results identify the STAT3-PKM2-HIF-1α/ROS axis as a key determinant of metabolic and phenotypic plasticity in hormone-independent breast and prostate cancers, highlighting its potential as a molecular target for therapeutic modulation of cancer-associated metabolic phenotypes.

Membranous and nuclear CD24 were expressed in the majority of mCRPC specimens, while NPY expression was more limited. NPY and nuclear CD24 were more highly expressed in AR+ mCRPC than AR- neuroendocrine disease, and nuclear CD24 displayed site-specific expression, suggesting a potential role for nuclear CD24 in promoting AR+ mCRPC.

This systematic review consolidates contemporary evidence regarding natural products as potential bioactive alternatives for modulating the androgen receptor (AR) signaling axis. Rather than providing a definitive clinical roadmap, this work establishes a preclinical framework for identifying substances that may deactivate the receptor, break down its resistant forms, or prevent nuclear translocation.

Overall, TH287 exhibited potent radiosensitization effects for CRPC treatment, effectively killing tumor cells when administered alongside IR at 12 h after the initial drug treatment.

P=N/A, N=25, Not yet recruiting, Institut Cancerologie de l'Ouest

P2, N=40, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2027 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2027

P1, N=453, Recruiting, Pfizer | Trial completion date: Mar 2029 --> Jul 2029