Castration-Resistant Prostate Cancer

Together, these observations support the integration of HSD3B1 into germline testing and clinical trials as it might help to identify groups at increased likelihood of benefiting from early, intensified, AR-targeting interventions. Lastly, 3βHSD1 is a promising target for pharmacological inhibition, which enables new strategies for systemic prostate cancer therapy.

Interpretation & conclusions Collectively, the findings of this study suggest that miR-363-3p may be a potential biomarker in differentiating individuals with PCa and CRPC from healthy controls. The miR-363-3p triggers various oncogenic genes (MDM2, NRAS, E2F3, CCNE2) and tumour suppressor genes (PTEN) that are actively involved in PCa progression and development.

This intriguing paradox - where both inhibition and activation of AR have anti-cancer effects - is now being harnessed clinically in the form of bipolar androgen therapy (BAT). This review describes mechanisms underlying the tumour-suppressive functions of AR in the context of potent androgenic stimulation and discusses how our maturing understanding of these mechanisms is influencing the clinical deployment of BAT.

D+T is active in mCRPC but patient selection remains a challenge. Further studies to develop predictive biomarkers are warranted.

This study revealed valuable findings for the clinical care of metastatic prostate cancer. Especially, predictive factors such as HRR defect in mCSPC should be validated in the future.

Germline pathogenic/likely pathogenic (P/LP) variants in BRCA2 and ATM genes are associated with a shorter time to progression and rarer P/LP variants in other DRG genes may play a role in mCRPC. This justifies the use of routine screening of men with advanced PrCa for germline variants and supports the need for an expanded panel test.

sTK1 was examined in three cohorts: (1) 43 men with de novo mHSPC managed with androgen deprivation monotherapy; (2) 99 patients with mCRPC managed with androgen receptor signaling inhibitors (ARSIs); and (3) 98 patients with mCRPC treated with docetaxel...We found that for patients with metastatic prostate cancer, high levels of a protein called TK1 that is involved in cell division was linked to higher risk of death. Our findings need to be confirmed in other studies.

P1, N=353, Completed, Eli Lilly and Company | Active, not recruiting --> Completed

Moreover, ATC-324 remains potent in enzalutamide-resistant PCa cells. These results demonstrate the potential of the AUTOTAC platform to target previously considered undruggable proteins and overcome certain drug resistance mechanisms.

P1, N=8, Active, not recruiting, Roswell Park Cancer Institute | Recruiting --> Active, not recruiting | N=18 --> 8 | Trial completion date: Jan 2025 --> Mar 2026

P2, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Sep 2024 --> Dec 2024

Introduction: TALAPRO-2 (NCT03395197) demonstrated that first-line talazoparib + enzalutamide significantly improved radiographic progression-free survival versus placebo + enzalutamide for patients with metastatic castration-resistant prostate cancer (mCRPC). These results are supportive of the ability of F1LCDx to sensitively detect alterations in HRR genes, and the likely overall modest impact of CHiP in calling HRR gene alteration status in this study. These results support the complementary benefits of ctDNA testing to tumor tissue testing in assessing current disease alteration status, particularly AR.

P1, N=18, Active, not recruiting, Washington University School of Medicine | Trial completion date: Mar 2026 --> Sep 2025

P1/2, N=150, Active, not recruiting, ESSA Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Jan 2025 | Trial primary completion date: Aug 2025 --> Oct 2024

P2, N=12, Completed, Abramson Cancer Center at Penn Medicine | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Feb 2024 | Trial primary completion date: Jun 2024 --> Feb 2024

P1, N=99, Active, not recruiting, ESSA Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Sep 2026 --> Jan 2025 | Trial primary completion date: Apr 2026 --> Oct 2024

P1, N=120, Recruiting, The Affiliated Hospital of Qingdao University

P2, N=20, Not yet recruiting, Xiangya Hospital of Central South University; Xiangya Hospital of Central South University

P1, N=92, Not yet recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

P1, N=63, Completed, Bayer | Active, not recruiting --> Completed

P1, N=48, Completed, Sumitomo Pharma Switzerland GmbH | Active, not recruiting --> Completed | N=72 --> 48 | Trial completion date: May 2025 --> May 2024 | Trial primary completion date: May 2025 --> May 2024

This is the first randomised phase 3 trial in the setting of PDT in patients with oligoprogressive mCRPC with OS as the primary endpoint.

Our results offer insights into the real-world application of CGP testing for patients with mCRPC at a cooperative hospital for cancer genomic medicine in Japan. Thus, urologists require a comprehensive understanding of the current status of CGP testing to enhance mCRPC management.

(Trial registration: ClinicalTrials.gov NCT04159896. Registration date: November 12, 2019.).

We previously developed and validated a signature reflecting low TSG expression (TSGlow) that was associated with poor outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) ± docetaxel...We found that patients with low expression of two out of three tumor suppressor genes (TP53, RB1, PTEN) had worse clinical outcomes and had aggressive variants of prostate cancer. Measuring the expression of these genes in early-stage prostate cancer could help in finding better treatments for these patients.

P3, N=430, Recruiting, Telix Pharmaceuticals (Innovations) Pty Limited | Not yet recruiting --> Recruiting

P=N/A, N=1574, Active, not recruiting, British Columbia Cancer Agency | Recruiting --> Active, not recruiting

The bioinformatic analysis revealed upregulation of anticancerogenic genes, downregulation of cancerogenic-related processes and pathways. Knocking down hsa-miR-192-5p in PC-3 cells resulted in downregulation of cancer cell proliferation, thus confirming these results.

P1, N=26, Active, not recruiting, University of Michigan Rogel Cancer Center | Recruiting --> Active, not recruiting

Nonetheless, recent breakthroughs in using natural derivatives to target AR and its splice variants have shown promise in treating chemoresistant castration-resistant prostate cancer (CRPC). This review will discuss the role of AR variants, particularly androgen receptor splice variant 7 (AR-V7), in CRPC and investigate the latest findings on how natural compounds and their derivatives target AR and AR splice variants.

P2, N=43, Recruiting, Andrew J. Armstrong, MD | Trial completion date: Jun 2027 --> Jun 2028 | Trial primary completion date: Dec 2024 --> Dec 2025

Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.

P1, N=66, Recruiting, Shenzhen Ionova Life Sciences Co., Ltd. | Not yet recruiting --> Recruiting

P3, N=528, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

P2, N=69, Recruiting, Australian and New Zealand Urogenital and Prostate Cancer Trials Group | Not yet recruiting --> Recruiting

P1, N=45, Recruiting, South Metropolitan Health Service (SMHS) | Not yet recruiting --> Recruiting

P2, N=223, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial primary completion date: Dec 2024 --> Mar 2025

P=N/A, N=167, Completed, Ipsen | Recruiting --> Completed | N=300 --> 167

P3, N=439, Active, not recruiting, Curium US LLC | Trial completion date: Jun 2029 --> Feb 2029

Because of the low FAP expression levels in CRPC, the utility of FAPi PET imaging may be limited. Although FAPi PET imaging may be further tested in PSMA-negative CRPC, such as small cell carcinoma, other molecular imaging modalities should be evaluated as alternative choices.

The identified genetic mutations and PSA levels have a moderate predictive ability for determining AR-V7 status.

The FDA recently approved olaparib and rucaparib for treating mCRPC patients with HRR gene alterations. Ongoing trials are investigating combination therapies involving PARP inhibitors combined with radiation, chemotherapy, immunotherapy, and androgen receptor signaling inhibitors (ARSIs) to improve the effectiveness of PARP inhibitors and broaden the range of patients who can benefit from the treatment. This review provides an overview of the development of PARP inhibitors in prostate cancer and analyzes the mechanisms underlying their resistance.