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After recent approvals, poly-adenosine diphosphate [ADP]-ribose polymerase inhibitors (PARPis) have emerged as a frontline treatment for metastatic castration-resistant prostate cancer (mCRPC). Unlike their restricted use in breast or ovarian cancers, where approval is limited to those with BRCA1/2 alterations, PARPis in mCRPC are applied across a broader spectrum of genetic aberrations. Key findings from the phase III PROPEL trial suggest that PARPis' accessibility may broaden, even without mandatory testing. An increasing body of evidence underscores the importance of distinct alterations in homologous recombination repair (HRR) genes, revealing unique sensitivities to PARPis. Nonetheless, despite the initial effectiveness of PARPis in treating BRCA-mutated tumors, resistance to therapy is frequently encountered. This review aims to discuss patient stratification based on biomarkers and genetic signatures, offering insights into the nuances of first-line PARPis' efficacy in the intricate landscape of mCRPC.
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http://dx.doi.org/10.3390/ijms25042184 | DOI Listing |
Clin Nucl Med
September 2025
Department of Radiology and Nuclear Medicine, Comprehensive Cancer Care and Research Center (SQCCCRC), University Medical City, Muscat, Oman.
PSMA-targeted radioligand therapies with 177Lu-PSMA-617 have shown promising response rates with favorable toxicity in patients with metastasized castration-resistant prostate cancer. We report a case of a 72-year-old man with metastatic castration-resistant prostate cancer having comorbidities of DM, HTN, and end-stage renal disease (ESRD) on regular hemodialysis. The patient received 2 doses of 7.
View Article and Find Full Text PDFJ Med Chem
September 2025
State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Resistance-conferring mutations in the androgen receptor (AR) ligand-binding pocket (LBP) compromise the effectiveness of clinically approved orthosteric AR antagonists. Targeting the dimerization interface pocket (DIP) of AR presents a promising therapeutic approach. In this study, we report the design and optimization of -(thiazol-2-yl) furanamide derivatives as novel AR DIP antagonists, among which was the most promising candidate.
View Article and Find Full Text PDFBJUI Compass
September 2025
Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine Kyoto University Kyoto Kyoto Japan.
Objectives: To develop a novel risk score (RS) model to predict the probability of progression to castration-resistant prostate cancer (PCa) (CRPC) after intensity-modulated radiation therapy (IMRT) for patients with high- and very high-risk PCa according to the National Comprehensive Cancer Network (NCCN) risk classification, since accurate prediction of the clinical outcome of definitive radiation therapy for patients with high- and very high-risk PCa remains challenging due to its heterogeneity.
Materials And Methods: We conducted a retrospective review of 600 patients with high- and very high-risk PCa treated with IMRT at our institution. They were randomly divided into discovery (n = 300) and validation (n = 300) cohorts.
J Chemother
September 2025
Eli Lilly Japan K.K, Kobe, Japan.
The aim of this Phase 1, multicentre, open-label study was to evaluate the safety, tolerability and pharmacokinetics (PK) of abemaciclib administered at global recommended Phase 2 dose (RP2D) of 200 mg twice daily, combined with standard doses of abiraterone and prednisolone, in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Dose-limiting toxicities (DLTs) were assessed for 28 days post-first dose. Six patients were treated, and all experienced at least one treatment-emergent adverse event (TEAE), mostly low grade; no Grade 4 or 5 TEAEs occurred.
View Article and Find Full Text PDFCancer Med
September 2025
The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, China.
Background: Prostate cancer is one of the principal malignancies threatening human health, and the development of castration resistance often constitutes a major cause of treatment failure in its management.
Methods: To elucidate the potential association between programmed death-ligand 1 (PD-L1) and castration resistance in prostate cancer, we analyzed the expression levels of PD-L1 in both primary prostate cancer tissues and castration-resistant prostate cancer (CRPC) specimens as well as in corresponding cell lines by using western blots and immunohistochemistry. Then, we explored the specific mechanisms through transcriptomic sequencing technology.