Prostate Cancer

Due to the poor prognosis of CDK12-mutant PCa patients and the mediocre response to classic standard therapies, HRD and increased neoantigen levels have provided clinicians with new insights into alternative systematic treatments for this novel PCa phenotype. In this review, we summarize the roles of CDK12 mutations in PCa and discuss their clinical value, suggesting that CDK12 potentially represents a target for further research and the development of clinical strategies for PCa.

PTOV1 and Cyfra21-1 are upregulated in LUAC patients who are resistant to neoadjuvant chemotherapy. Both markers not only have predictive value for chemosensitivity in these patients, but are also independent factors affecting neoadjuvant chemosensitivity.

Lastly, NKX2-1/FOXA2 interacts with, and recruits CBP/p300 proteins to activate NE enhancers, and pharmacological inhibitors of CBP/p300 effectively blunted NE gene expression and abolished NEPC tumor growth. Thus, our study reports a hierarchical network of TFs governed by NKX2-1 in regulating the 2D and 3D chromatin re-organization during NET and uncovers a promising therapeutic approach to eradicate NEPC.

The lncRNA MIR503HG acts as an oncogenic regulator in PCa by repressing cellular senescence. SAL-induced suppression of MIR503HG enhances the tumor-suppressive effects of AR signaling, suggesting that MIR503HG could serve as a biomarker for BAT responsiveness and as a target for combination therapies with PARP inhibitors.

We identified MS4A1 as a promising biomarker for the diagnosis of PCa-related fatigue. Our findings would lay a foundation for revealing the pathogenesis and developing therapies for PCa-related fatigue.

The results demonstrate that this test can accurately quantitate the level of promoter methylation at the BRCA1 and RAD51C genes using FFPE samples, even when the extracted DNA is extremely degraded or the input amount is limited. This test increases the precision of diagnostic tests aimed at identifying patients who are likely and unlikely to respond to PARP inhibitor therapy.

P1, N=8, Recruiting, Hoag Memorial Hospital Presbyterian

P1, N=30, Recruiting, Amgen | Not yet recruiting --> Recruiting

P=N/A, N=100, Recruiting, Case Comprehensive Cancer Center | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=22, Completed, Ultimovacs ASA | Active, not recruiting --> Completed

P2, N=166, Terminated, SOTIO Biotech AG | Active, not recruiting --> Terminated; Due to lack of expected efficacy shown at the time of the interim analysis

P2, N=25, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

Gene signatures driven by ARE activity correlate with improved prognosis and luminal phenotypes in PCa patients. Canonical AREs maintain a normal, lineage-specific transcriptional program that can be reengaged in PCa cells, offering therapeutic potential and clinical relevance.

Finally, we have offered the current attempts of chronotherapy targeting CSCs. Elucidating the molecular regulation of circadian clock gene in CSCs will provide us a novel direction for the development of therapeutics to target CSCs.

This study identified a list of AR/SRF common interactors that represent a pipeline of druggable targets for the treatment of PCa.

Androgen receptor (AR) signaling is the principal driver of prostate cancer, and drugs that target this pathway (e.g., abiraterone and enzalutamide) are standard treatments for metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer (mCRPC). These promising preclinical data supported clinical development of bavdegalutamide as a potential treatment for patients with prostate cancer. Bavdegalutamide was the first PROTAC protein degrader to enter human clinical trials, specifically in patients with mCRPC in a phase 1/2 study (NCT03888612).

In the present review, the developmental course, composition and mechanism of action of ADCs are explored, with a specific focus on recently published studies and ongoing trials aimed at investigating the efficacy and safety of ADCs in treating PCa. Lastly, ongoing challenges in ADC development and corresponding strategies to combat them are discussed.

P=N/A, N=104, Not yet recruiting, Pfizer

P=N/A, N=25, Recruiting, University of Texas Southwestern Medical Center | Not yet recruiting --> Recruiting

P2, N=25, Not yet recruiting, University of Florida | Initiation date: Nov 2024 --> Feb 2025

P1, N=174, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Apr 2025 --> May 2029 | Trial primary completion date: Dec 2024 --> Aug 2025

P=N/A, N=1000, Recruiting, Mayo Clinic | N=300 --> 1000

P4, N=600, Not yet recruiting, Roswell Park Cancer Institute

Patients with higher PPP1R14B expression responded more sensitively to drugs selumetinib and vorinostat, zebularine, azacitidine and VER155008. In summary, PPP1R14B was a potential diagnostic and prognostic biomarker of PCa and its high expression had closely association with tumor immune inhibition, proliferation and migration, providing a new target for drug therapy and immunotherapy in PCa.

Increasing PCA3 level was associated with any APFs except perineural invasion in our study, which comprised mostly of intermediate and high-risk prostate cancer patients. Therefore, PCA3 could be used as an adjunctive measure in selecting patients for definitive treatments.

P=N/A, N=12, Not yet recruiting, Edith Cowan University

P=N/A, N=60, Completed, Edith Cowan University | Recruiting --> Completed

P2, N=32, Recruiting, University of Utah | Not yet recruiting --> Recruiting

P=N/A, N=24, Completed, UNC Lineberger Comprehensive Cancer Center | Recruiting --> Completed

Three novel feed-back loops and a novel AR- BHLHE40 / LYL1 -p27kip1 axis has been identified mediating cellular senescence in PCa cells.

Notable activities of linichlorin B, cynaropicrin, and aguerin B (with IC50 values of 13.67 μg/ml, 6.79 μg/ml, and 3.46 μg/ml, respectively) were detected in the PC-3 cell line; aguerin B demonstrated activity most comparable to the standard anticancer agent doxorubicin. Likewise, linichlorin B, aguerin B, and cynaropicrin demonstrated notable efficacy in the HeLa and MCF-7 cell lines, as reported by the American National Cancer Institute. Aguerin B, linichlorin B, and cynaropicrin are projected to serve as promising novel chemotherapeutic agents for cancer therapy.

TBx samples yield higher genomic scores than SBx samples, with grade influencing the association between PI-RADS score and genomic risk. For the GG 1 subgroup, there was no correlation between PI-RADS and genomic scores. These findings need further validation to assess the impact of TBx on genomic risk assessment in active surveillance.

The elevated M-CSF levels in serum and urine at baseline were associated with the deterioration of QoL during radiotherapy. The results of this study may help to develop mitigation strategies to limit radiation damage to the bladder.

We also identify a conformational shift upon EPI-001 binding to the TAU-5, and to a much lesser extent with TAU-1 containing constructs. This work provides novel insight on the interactions of EPI-001 with the AR-NTD, and the structural alterations that it exerts, and positions IM-MS as an informative tool that will enhance the tractability of IDPs, potentially leading to better therapies.

Following diagnosis, the typical life expectancy ranges from 12 to 15 months, as current established treatments like surgical intervention, radiotherapy, and chemotherapy using temozolomide exhibit limited effectiveness...We delineate the receptors it binds to and its significance in glioblastoma and other cancer types. Lastly, we examine its role in immunotherapy and the utilization of nanobodies in this domain.

P=N/A, N=278, Not yet recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2027 --> Mar 2029 | Initiation date: Oct 2024 --> May 2025 | Trial primary completion date: Jul 2027 --> Mar 2029

P=N/A, N=300, Recruiting, Ministry of Science and Technology of the People´s Republic of China

P1, N=126, Completed, University of Wisconsin, Madison | Recruiting --> Completed

However, results were based on few distinct study populations and generally had low precision, underscoring the need for replication. In conclusion, prostate cancer with TMPRSS2:ERG fusion is an etiologically distinct subtype that may be, in part, preventable by addressing modifiable and hormonally acting etiologic factors that align with the established mechanistic role of TMPRSS2:ERG in androgen, insulin, antioxidant, and growth factor pathways.

P1, N=232, Recruiting, Bayer | N=140 --> 232

P=N/A, N=43, Completed, Sidney Kimmel Cancer Center at Thomas Jefferson University | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> Jul 2024 | Trial primary completion date: Nov 2024 --> Jun 2024

We develop a custom targeted cfDNA sequencing assay, named AR-ctDETECT, to detect ctDNA in limiting plasma cfDNA available from mCRPC patients in the Alliance A031201 randomized phase 3 trial of enzalutamide with or without abiraterone. ctDNA-positive patients have significantly worse median overall survival than ctDNA-negative patients (29.0 months vs. 47.4 months, respectively). Here, we show that mCRPC patients identified as ctDNA-positive using the AR-ctDETECT assay have poor survival despite treatment with potent AR inhibitors in a phase 3 trial.