enzalutamide

We retrospectively analyzed 148 patients with mHSPC treated with either ARPI (abiraterone, enzalutamide, or apalutamide) plus androgen deprivation therapy (ADT) (n = 98) or docetaxel plus ADT (n = 50). In this real-world cohort, ARPI-based therapy was associated with an improvement in rPFS compared with docetaxel, while OS outcomes remained comparable. In the absence of direct randomized comparisons, these findings may provide supportive real-world evidence for the clinical relevance of ARPI-based therapy as a first-line treatment option for patients with mHSPC.

P2, N=50, Recruiting, Sean Sachdev | Trial primary completion date: Nov 2028 --> Nov 2030

Mechanistically, ENZ blocked AR-mediated transcriptional activation of MCM4, a critical component of the DNA helicase complex, thereby enhancing the effect of CDK4/6 inhibition on DNA replication and inducing a pronounced synergistic antitumor response. These results suggest that the ENZ-DAL combination is a promising therapeutic approach that warrants further clinical evaluation in CRPC patients.

Leveraging these insights, we perform structure-based virtual screening based on the identified druggable conformations and identify K53, a rationally designed AR-NTD antagonist, which exhibits potent anti-proliferative activity in enzalutamide-resistant prostate cancer cells. K53 directly binds the AR-NTD, suppresses AR transcriptional activity, and demonstrates high selectivity for cancer cells. This work provides a rational design paradigm for targeting intrinsically disordered proteins and offers a therapeutic candidate for resistant prostate cancer.

P2, N=132, Recruiting, University Health Network, Toronto | Trial completion date: Mar 2026 --> Feb 2031 | Trial primary completion date: Mar 2026 --> Feb 2031

P2, N=53, Recruiting, Syntrix Biosystems, Inc. | Trial primary completion date: Jun 2026 --> Jun 2027

P3, N=5000, Not yet recruiting, Exelixis

P1/2, N=212, Recruiting, Qilu Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

APOL3 is a central driver of PCa aggressiveness and enzalutamide resistance, functioning via the direct modulation of the DAB2IP/STAT3 axis and the activation of the GR bypass pathway. Cotargeting APOL3 alongside DAB2IP restoration represents a highly promising, synergistic therapeutic strategy to circumvent adaptive resistance and halt metastatic progression in advanced castration-resistant prostate cancer.

Talazoparib added to enzalutamide led to significantly better imaging-based progression-free survival than placebo plus enzalutamide among patients with metastatic APMS prostate cancer harboring alterations in homologous recombination repair genes. Serious adverse events were more common with talazoparib plus enzalutamide than with placebo plus enzalutamide. (Funded by Pfizer; TALAPRO-3 ClinicalTrials.gov number, NCT04821622.).

Collectively, our findings implicate Kaiso as a key player in TNBC and QNBC, highlighting its potential as a druggable target for improving outcomes in these aggressive breast cancer subtypes.

To antagonize the ACSL4-conferred ferroptosis risk, SCL/NEL cells upregulated GPX4 through AP-1 transcription complex to suppress ferroptosis and thus promoted the malignant progression of SCL/NEL cells. Notably, we characterized Auranofin, an anti-rheumatoid arthritis drug, as a ferroptosis inducer for these SCL/NEL cells in vitro and in vivo by targeting AP-1 and decreasing GPX4 expression, suggesting a new application for Auranofin in treating enzalutamide-resistant stem cell-like AP-1High CRPC.