bims-meproc Biomed News
on Metabolism in Prostate Cancer
Issue of 2026–01–25
forty-six papers selected by
Grigor Varuzhanyan, UCLA
  1. Androgen receptor contributes to radioresistance through DNA repair and autophagy in AR-positive prostate cancer cells.
  2. Retraction: Mitostatin is down-regulated in human prostate cancer and suppresses the invasive phenotype of prostate cancer cells.
  3. RIPK2 induces docetaxel resistance in prostate cancer through the NF-κB/P-gp signaling pathway.
  4. MYC-driven TRIM27 upregulation promotes prostate cancer progression by enhancing CANX ubiquitination and activating PI3K/AKT signaling.
  5. Cytotoxic and anti-metastatic effects of Pllans-II from Porthidium lansbergii lansbergii venom against prostate cancer cells.
  6. Integrative transcriptomic profiling reveals subtype-specific therapeutic vulnerabilities and resistance mechanisms in prostate cancer.
  7. RNA-Binding Protein NF90 Mediates Polycomb-Independent Transactivation by EZH2 to Promote Cancer Growth.
  8. TBX21 correlates with an immunosuppressive tumor microenvironment and Treg/Th17 imbalance in prostate cancer.
  9. Neuregulin induces prostate cancer cell migration via HER3/HER2-FAK/Src signaling axis.
  10. Action mechanism of Qianlie Xiaozheng decoction against prostate cancer: network pharmacology, molecular docking, and molecular dynamics simulations.
  11. Loss of biomechanical features reveals smooth muscle disruption and disease progression in prostate cancer.
  12. Exploring the Therapeutic Potential of Processed Citrus reticulata Peel Extracts in the Treatment of Prostate Cancer and Benign Prostatic Hyperplasia.
  13. A novel protein encoded by circIMP3 promotes prostate cancer progression by regulating alternative splicing and tumor microenvironment.
  14. The predictive value of necroptosis-related lncRNAs in prostate cancer prognosis and their potential to distinguish between cold and hot tumors.
  15. Identify GDPD3 as a key regulator of epithelial-mesenchymal transition and prostate adenocarcinoma progression via the LPA/LPAR1/AKT axis: transcriptomic and experimental study.
  16. Microenvironment-Guided Evolution of ssDNA-SWCNT Probes for Selective Recognition of Aggressive Prostate Cancer Phenotypes.
  17. Integrating Proteomics and Predictive Model: Elucidating the Role of Aminated Nanodiamonds in Suppressing Prostate Cancer Growth.
  18. Inflammation Beyond the Prostate: The Role of Systemic Inflammatory Disorders in Prostate Carcinogenesis.
  19. Inhibition of LONP1 in prostate cancer: bibliometrics-guided target screening and AI-driven antibody design.
  20. Identification of prognostic biomarkers and development of a prediction model for prostate cancer.
  21. Compound Library Screening Identified Cladribine as a Novel Radiosensitizer for Prostate Cancer.
  22. The role of neuroendocrine differentiation in treatment resistance of prostate cancer and intervention strategies.
  23. Boolean network-based identification of optimal drug combinations for prostate cancer.
  24. Combination prostate cancer therapy via CuTCPP-MOF-mediated chemodynamic and photodynamic effects.
  25. Cellular signaling and radioresistance in prostate cancer.
  26. Fat quality, not quantity, linked to reduced risk of advanced and lethal prostate cancer in US populations: a large prospective multicenter study.
  27. Long Noncoding RNA ST8SIA6-AS1 Promotes the Development of Prostate Cancer by Activating the TGF-β/Smad Signaling Pathway through Regulating the miR-18a-5p/TGFBR1 Axis.
  28. Targeting glycolysis in prostate cancer: Molecular mechanisms and therapeutic advances.
  29. Combined prostate cancer vaccine plus immune checkpoint inhibition synergizes to eliminate prostate cancer.
  30. Clinical hurdles for curcumin and piperine nanoparticles in prostate cancer treatment: a bridge too far or a path to clinical reality?
  31. Diversity of Gut Microbiota and Metabolites in Benign Prostatic Hyperplasia with Different Prostate Volumes.
  32. Current landscape and therapeutic prospects of indole hybrids for prostate cancer treatment: A mini-review.
  33. Multi-stimuli activated PROTAC prodrug for controlled protein degradation with enhanced therapeutic effects.
  34. Identification of a Cuproptosis-Related Molecular Signature for Predicting Biochemical Recurrence in Prostate Cancer.
  35. Computational Analysis and in vitro Validation of the Anti-Prostate Cancer Activity of Sesamin from Sesamum indicum.
  36. Time-Resolved Förster Resonance Energy Transfer Nanoassay Based on CdTe Quantum Dots for Sensitive Detection of Prostate Cancer Antigen 3.
  37. Correction to "FOXS1 Acts as an Oncogene and Induces EMT Through FAK/PI3K/AKT Pathway by Upregulating HILPDA in Prostate Cancer".
  38. Polyploid cisplatin-resistant cancer cells have altered nuclear organization and epigenomic status.
  39. Association between red blood cell distribution width to albumin ratio and prostate specific antigen based on NHANES data.
  40. PSMA RNA aptamer A10-3.2 conjugated with indocyanine green for rapid intraoperative imaging and effective mild photothermal therapy of prostate cancer.
  41. Natural product-mediated autophagy targeting for prostate cancer: A novel potential therapeutic strategy.
  42. Folate-Functionalized Polymeric Nanoparticles for 5‑Fluorouracil Delivery to Prostate Cancer: Physicochemical and In Vitro/In Vivo Characterization.
  43. MRI prostate tumor volume predicts the need for systematic biopsies in patients undergoing MRI-targeted biopsy.
  44. [Therapy-Associated Neuroendocrine Prostate Cancer (tNEPC): A Diagnostic and Therapeutic Challenge in Uro-Oncology with Emerging Clinical Implications].
  45. European Study of Prostate Cancer Screening - 23-Year Follow-up.
  46. Synergistic treatment of prostate cancer and multiple myeloma using CD46-targeted radioimmunotherapy-antibody drug conjugates.
  1. bioRxiv. 2025 Dec 05. pii: 2025.12.03.690226. [Epub ahead of print]
    Androgen receptor contributes to radioresistance through DNA repair and autophagy in AR-positive prostate cancer cells.
    Ken-Ichi Kudo, Qianhua Feng, Maria Isabel Chosco, Jonathan M Anzules, Ziyi Huang, Kavya Achanta, Leslie Wenning, Jeshwanth Mohan, June-Wha Rhee, Maedeh Mohebnasab, Evita Sadimin, Zhao V Wang, Yun Rose Li.
      Androgen receptor (AR) is a critical therapeutic target in prostate cancer (PCa), and androgen blockade is known to act synergistically with radiation therapy. However, the mechanisms through which AR modulates radiation response are not yet fully understood. In this study, we aimed to investigate the role of AR in mediating radioresistance in PCa. AR-positive LNCaP and castration-resistant C4-2 cells exhibited significantly higher radioresistance than AR-negative cells, as determined by apoptosis and cell viability assays. Following irradiation, most LNCaP cells were arrested in the G1 phase, accompanied by rapid p53 activation and p21 induction. Consistently, AR silencing significantly increased radiosensitivity and reduced DNA-PKcs expression and phosphorylation, suggesting that AR enhances DNA repair, likely through non-homologous end joining (NHEJ). At the cellular level, irradiation markedly induced macroautophagy in LNCaP and C4-2 cells, as evidenced by increased LC3B-II accumulation and autophagic vacuole formation, and the upregulation of 11 autophagy-related genes was identified by whole-transcriptomic analysis. To assess their functional relevance, we performed siRNA-mediated knockdown of selected autophagy-related genes and assessed cell viability and Annexin V/PI staining. Notably, BECN1 and LC3 knockdown significantly enhanced radiosensitivity, with BECN1 knockdown showing an effect comparable to that observed with AR silencing. These results suggest that radiation-induced autophagy promotes the survival of AR-positive prostate cancer cells. Moreover, immunohistochemical analysis of ex vivo- irradiated, patient - derived PCa tissues from patients with newly diagnosed high - Gleason score prostate cancer undergoing prostatectomy further demonstrated that radiation-induced autophagy supports the survival of high-grade AR-positive tumor cells. Collectively, our findings reveal that AR promotes radioresistance in PCa by enhancing both DNA repair and autophagy.
    DOI:  https://doi.org/10.64898/2025.12.03.690226
  2. PLoS One. 2026 ;21(1): e0341382
    Retraction: Mitostatin is down-regulated in human prostate cancer and suppresses the invasive phenotype of prostate cancer cells.
    PLOS One Editors
      
    DOI:  https://doi.org/10.1371/journal.pone.0341382
  3. PLoS One. 2026 ;21(1): e0341445
    RIPK2 induces docetaxel resistance in prostate cancer through the NF-κB/P-gp signaling pathway.
    Shaoqiang Xing, Zhaoliang Xu, Sheng Zeng, Minghao Yue, Wenzhou Xing, Qian Liu.
      Chemoresistance is a reason for treatment failure in prostate cancer. Receptor-interacting protein kinase 2 (RIPK2) has been shown to play a role in drug resistance in various cancers; however, its role and the underlying mechanism of chemoresistance in prostate cancer are unclear. We analyzed data from The Cancer Genome Atlas for RIPK2 expression in prostate cancer and its association with clinicopathological features. We also elucidated the role and mechanism of action of RIPK2 in prostate cancer cell resistance to docetaxel (DTX). The results showed that RIPK2 expression was upregulated in prostate cancer tissues and was associated with poor pathological grading. RIPK2 was also upregulated in 22RV1/DTX, C4-2/DTX, PC-3/DTX, and DU145/DTX cell lines and involved in DTX resistance. Mechanistic experiments revealed that RIPK2 was involved in DTX resistance by upregulating P-glycoprotein (P-gp) expression through the activation of the NF-κB signaling pathway. Xenograft tumor experiments confirmed that inhibition of RIPK2 or P-gp enhanced the efficacy of DTX in suppressing PC-3/DTX growth. Taken together, these results suggest that RIPK2 mediates DTX resistance in prostate cancer cells through the NF-κB/P-gp signaling pathway. RIPK2 and its downstream signaling molecules are potential targets for the treatment of chemoresistant prostate cancer.
    DOI:  https://doi.org/10.1371/journal.pone.0341445
  4. Funct Integr Genomics. 2026 Jan 20. 26(1): 29
    MYC-driven TRIM27 upregulation promotes prostate cancer progression by enhancing CANX ubiquitination and activating PI3K/AKT signaling.
    Zitao Wang, Jinzhuo Ning, Lizhe Xu, Fan Cheng.
      
    Keywords:  Biomarker; CANX; Prostate cancer; TRIM27; Ubiquitination
    DOI:  https://doi.org/10.1007/s10142-025-01811-x
  5. Biochem Biophys Res Commun. 2026 Jan 17. pii: S0006-291X(26)00071-9. [Epub ahead of print]800 153307
    Cytotoxic and anti-metastatic effects of Pllans-II from Porthidium lansbergii lansbergii venom against prostate cancer cells.
    Cesar Vela-Prieto, Mildrey Mosquera Escudero, Alejandro Montoya-Gómez, Eliécer Jiménez-Charris.
      Prostate cancer remains a major health challenge due to therapeutic resistance and the adverse effects of conventional treatments. Snake venom phospholipases A2 have emerged as promising bioactive molecules with selective anti-cancer properties. In this study, we evaluated the cytotoxic and anti-metastatic effects of Pllans-II, an Asp-49 PLA2 purified from Porthidium lansbergii lansbergii venom, on prostate cancer cell lines. Pllans-II exerted a dose-dependent cytotoxic effect on LNCaP, PC-3, and DU-145 cells, with the strongest activity observed in LNCaP cells (IC50 = 100 μg/mL). In contrast, it spared non-tumorigenic prostate epithelial cells (PCS-440-010), unlike Docetaxel. Pllans-II did not compromise plasma membrane integrity, suggesting a non-lytic mechanism of action. Functional assays revealed that Pllans-II significantly inhibited LNCaP cell migration in both 2D wound-healing and 3D transwell models, reduced adhesion to fibronectin and Matrigel, and impaired clonogenic capacity. Western blot analysis revealed no change in the caspase-8 expression, but a marked upregulation of Beclin-1, probably related to autophagy cell death pathways. These findings highlight the selective cytotoxicity and anti-metastatic potential of Pllans-II, positioning it as a promising prototype for the development of novel therapeutic strategies against prostate cancer.
    Keywords:  Anticancer activity; Autophagy; Bioprospecting; Drug discovery; Snake venom
    DOI:  https://doi.org/10.1016/j.bbrc.2026.153307
  6. BMC Cancer. 2026 Jan 21. 26(1): 97
    Integrative transcriptomic profiling reveals subtype-specific therapeutic vulnerabilities and resistance mechanisms in prostate cancer.
    Wei Liu, Weiyu Kong, Silin Jiang, Yong Wei, Zijie Yu, Xiaoyang Cao, Jian Yang, Xiyi Wei, Luming Shen, Chao Qin, Qingyi Zhu.
       OBJECTIVE: Advanced prostate cancer (PCa) remains therapeutically challenging due to heterogeneous mechanisms of resistance to androgen receptor (AR)-targeting agents. While AR signaling persists in castration-resistant PCa (CRPC), emerging evidence suggests AR-independent survival pathways may contribute to therapeutic escape. This study integrates transcriptomic data and clinical profiling to dissect AR dependency and resistance mechanisms in PCa, aiming to identify subtype-specific vulnerabilities and therapeutic targets.
    METHODS: We performed CRISPR-Cas9 screens in AR-dependent (VCaP, LNCaP, 22Rv1) and AR-independent (DU145, PC-3, WPE1-NA22, P4E6, Shmac5) cell lines to identify core essential genes. RNA sequencing data from TCGA-PRAD, Changhai, and DKFZ cohorts were integrated to define molecular subtypes using consensus clustering. Spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) were employed to validate gene expression patterns in primary tumors and metastatic samples. Temporal expression dynamics were analyzed using fuzzy clustering to identify resistance mediators, with a focus on MCL1. Drug sensitivity analysis revealed that AR-dependent cells were more sensitive to MCL1 inhibitor UMI-77, and MCL1 expression was higher in Enzalutamide-resistant cell lines. Functional validation via MCL1 knockdown confirmed its role in supporting the proliferation and inhibiting apoptosis of resistant cells.
    RESULTS: CRISPR screening identified 952 shared essential genes in prostate cancer, with 157 AR-high essential signature and 130 AR-low essential signature genes. AR-high essential signature genes enriched in cell cycle/polycomb pathways, while AR-low essential signature genes correlated with oxidative phosphorylation/mTOR signaling. Consensus clustering of TCGA-PRAD data revealed three molecular subtypes (Clusters 1-3); Cluster 3 showed worst prognosis (shorter PFI/OS) and advanced clinical features (higher T/N stage, Gleason grade). External validation confirmed Cluster 3's aggressive phenotype and independent prognostic value (meta-cohort HR = 1.98, 95% CI: 1.19-3.27). Cluster 3 signature genes were upregulated in metastatic/CRPC tissues and spatially enriched in CRPC epithelium. Notably, Cluster 3 shared essential gene expression decreased after Enzalutamide treatment, whereas AR-high essential signature genes remained stable. MCL1 emerged as a key resistance driver, demonstrating persistent upregulation in Enzalutamide-resistant cells and CRPC models.
    CONCLUSIONS: This study elucidates distinct AR dependency landscapes in PCa, revealing AR-independent survival pathways and a clinically actionable molecular subtype (Cluster 3) linked to therapy resistance. MCL1 emerges as a critical mediator of adaptive resistance, highlighting the need for combination therapies targeting both AR-driven and AR-independent programs to improve outcomes in advanced PCa.
    Keywords:  CRISPR-Cas9 screen; Enzalutamide resistance; MCL1; Multi-omics; Prostate cancer
    DOI:  https://doi.org/10.1186/s12885-025-15357-5
  7. bioRxiv. 2025 Dec 03. pii: 2025.12.02.691892. [Epub ahead of print]
    RNA-Binding Protein NF90 Mediates Polycomb-Independent Transactivation by EZH2 to Promote Cancer Growth.
    Yuan Wang, Liu Peng, Xiaodong Lu, Hongshun Shi, Mohan Zheng, Sambhavi Senthil, Jawad Akhtar, Yongik Lee, Hana Chandonnet, Jonathan D Licht, Ximing Yang, Jonathan C Zhao, Jindan Yu.
      Increasing evidence suggests critical roles of the polycomb-independent transactivation function of EZH2 in promoting some cancers, such as prostate cancer (PCa), yet the underlying mechanism remains poorly understood. Here, we identify the RNA-binding protein NF90 as a key mediator of this activity. NF90 interacts with EZH2, but not with other core components of the polycomb repressive complex 2 (PRC2), through its RNA-binding modules. Conversely, EZH2 engages NF90 via its intrinsically disordered RNA-binding domain in an RNA-dependent manner. NF90 and EZH2 mutually recruit each other to the AR promoter, where they cooperatively activate AR transcription and enhance downstream AR signaling. This NF90-EZH2 complex is essential for PCa cell growth: depletion of either factor abolishes proliferation, an effect rescued by AR re-expression. Similar to EZH2, NF90 promotes cell-cycle gene expression, is upregulated in advanced PCa, and is associated with poor clinical outcomes. Collectively, our findings uncover RNA-mediated protein interactions as a central mechanism underlying PRC2-independent transcriptional activation by EZH2 and establish NF90 as a major EZH2 coactivator, a master regulator of the cell cycle, and a promising therapeutic target in advanced PCa.
    DOI:  https://doi.org/10.64898/2025.12.02.691892
  8. Front Oncol. 2025 ;15 1701148
    TBX21 correlates with an immunosuppressive tumor microenvironment and Treg/Th17 imbalance in prostate cancer.
    Heng Wang, Zhaofei Liu, Xiangjun Xu, Qichao Wang, Pingan Chang, Lei He, Jun Ouyang.
       Background: Prostate cancer (PCa) remains a major health burden, and identifying target molecules will provide new research ideas for treating PCa. TBX21 is a transcriptional factor with critical functions in tumor development, roles of which in PCa were studied herein.
    Methods: TBX21 expression was evaluated by RNA-seq, RT-PCR, Western blot, and immunohistochemistry in PCa tissues and cell lines. Functional assays were performed using LNCaP and 22RV1 cells with TBX21 knockdown to assess proliferation and apoptosis. Tumor growth and immune alterations were examined in xenograft and humanized immune cell models, while flow cytometry and Western blot were used to characterize immune cell subsets and effector molecules.
    Results: TBX21 expression was significantly elevated in PCa tissues and cell lines. TBX21 knockdown was associated with reduced proliferation and increased apoptosis in vitro and suppressed tumor growth in vivo. In humanized xenografts, TBX21 silencing was accompanied by a decrease in regulatory T cells (Treg) and an increase in Th17 and cytotoxic CD8+ T cells, together with enhanced expression of effector molecules (TNF-α, GZMB). Co-culture experiments showed that TBX21-deficient tumor cells reduced the induction of CD25+Foxp3+ Treg cells from activated CD4+ T cells.
    Conclusion: TBX21 is associated with tumor progression and an immunosuppressive microenvironment in PCa, underscoring its potential role in modulating the tumor-immune balance.
    Keywords:  TBX21; Treg; immune microenvironment; immunosuppression; prostate cancer
    DOI:  https://doi.org/10.3389/fonc.2025.1701148
  9. Cancer Cell Int. 2026 Jan 21.
    Neuregulin induces prostate cancer cell migration via HER3/HER2-FAK/Src signaling axis.
    Eun Jin Lim, Yu Jeong Yoon, Yehwon Kim, Hyung Hwan Moon, Yung-Hyun Choi, Young-Ho Kim.
      
    Keywords:  Cell migration; Epithelial-mesenchymal transition; HER3; Neuregulin-1; Prostate cancer; Snail
    DOI:  https://doi.org/10.1186/s12935-026-04186-6
  10. Comput Methods Biomech Biomed Engin. 2026 Jan 19. 1-12
    Action mechanism of Qianlie Xiaozheng decoction against prostate cancer: network pharmacology, molecular docking, and molecular dynamics simulations.
    Xing Fu.
      Prostate cancer (PCa) is a leading male malignancy. This study explores the anti-PCa mechanism of Qianlie Xiaozheng decoction (QLXZD) using network pharmacology. From 34 ingredients and 23 potential therapeutic targets, 3 hub ingredients (baicalein, kaempferol, quercetin) and 4 hub targets (CCNB1, CDK1, EGFR, TOP2A) were prioritized. Enrichment analysis of the 23 targets linked them to cell cycle and kinase signaling. Molecular docking confirmed strong binding of the hub ingredients to the hub targets, comparable to known inhibitors. Molecular dynamics simulations supported baicalein-TOP2A complex stability. These findings reveal QLXZD exerts anti-PCa effects via a multi-component, multi-target mechanism, supporting its clinical application.
    Keywords:  Qianlie xiaozheng decoction; molecular docking; network pharmacology; prostate cancer; traditional Chinese medicine
    DOI:  https://doi.org/10.1080/10255842.2026.2617941
  11. Cancer Cell Int. 2026 Jan 20.
    Loss of biomechanical features reveals smooth muscle disruption and disease progression in prostate cancer.
    Yu Luo, Chengcheng Wei, Zixiong Jiang, Zhangcheng Liu, Jingke He, Liangdong Song, Wenjun Zhou, Kun Han, Yunfan Li, Jindong Zhang, Xiaoqi Deng, Jue Wang, Shuai Su, Delin Wang.
       BACKGROUND: Biomechanical features show notable heterogeneity in tumor risk stratification, yet their role in prostate cancer (PCa) progression remains unclear. This study aimed to elucidate the role and underlying mechanism of biomechanical features in PCa progression.
    METHODS: We integrated transcriptomic data from 1693 PCa patients across ten public cohorts and single-cell RNA sequencing (scRNA-seq) data from 19 PCa samples to define biomechanical subtypes. RT-qPCR was used to assess the impact of mechanical stimulation on malignant phenotypes. Biomechanical regulatory genes (BMRGs) were identified using consensus clustering and Weighted Gene Co-expression Network Analysis (WGCNA). A prognostic index (MRPX) was developed using machine learning. Immune infiltration and drug sensitivity analyses were conducted to assess the clinical utility of MRPX in guiding precision therapy. A co-culture model was employed to assess the impact of COL5A1-positive fibroblasts on the metastatic potential of PCa cells.
    RESULTS: Loss of biomechanical features was associated with smooth muscle disruption and PCa progression. In vitro mechanical stimulation suppressed EMT-related gene expression in PC-3 cells. WGCNA identified 137 hub BMRGs, from which MRPX was constructed. MRPX demonstrated strong generalizability in predicting PCa progression and effectively stratified patient responses to both immunotherapy and chemotherapy. Elevated MRPX was associated with smooth muscle disruption, which linked MRPX to extracapsular extension (ECE) and enhanced metastatic potential. Mechanistically, COL5A1 was closely linked to PCa progression, and CellChat analysis indicated that COL5A1⁺ fibroblasts contribute to shaping an aggressive tumor microenvironment. Co-culture experiments confirmed a marked upregulation of COL5A1 in cancer-associated fibroblasts (CAFs). Furthermore, silencing of COL5A1 significantly attenuated the ability of CAFs to promote the metastatic potential of PC-3 cells.
    CONCLUSIONS: This study establishes MRPX as a robust biomarker for prognostic stratification and therapeutic guidance in PCa, offering new insights into biomechanical regulation of tumor progression and providing a potential avenue for precision oncology.
    Keywords:  Biomechanical feature; Machine learning; Multi-omics; Prostate cancer; Risk stratification
    DOI:  https://doi.org/10.1186/s12935-026-04169-7
  12. Curr Pharm Des. 2026 Jan 09.
    Exploring the Therapeutic Potential of Processed Citrus reticulata Peel Extracts in the Treatment of Prostate Cancer and Benign Prostatic Hyperplasia.
    Cheng-Yang Hsieh, Khyle Suratos, Ching-Chiung Wang, Lemmuel Tayo, Paolo Robert Bueno, Mon-Juan Lee, Agnes Alimboyoguen, Po-Wei Tsai.
       BACKGROUND: Citrus reticulata (CR) has a long-standing role in traditional medicine, primarily due to its bioactive constituents such as hesperidin and narirutin, which are known for their antioxidant, antiinflammatory, antibacterial, and anticancer properties.
    OBJECTIVE: This study investigates the anti-proliferative activity of CR water extracts against DU-145 prostate cancer cells and explores the therapeutic potential and underlying molecular mechanisms of hesperidin and narirutin in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) through network pharmacology and molecular docking approaches.
    METHODS: Cytotoxicity assays were employed to determine the anti-cancer efficacy (IC50) of processed CR water extracts in DU-145 cells. Targets related to hesperidin, narirutin, PCa, and BPH were identified using bioinformatics platforms. Network pharmacology was applied to construct compound-target interaction networks and perform enrichment analyses (GO, KEGG, and DisGeNET) to elucidate key signalling pathways. Molecular docking was conducted to validate compound-target interactions.
    RESULTS: Soil-processed CR extracts exhibited the strongest anti-cancer activity (IC50 = 1.789 mg/mL). Enrichment analyses identified significant pathways, including AGE-RAGE signalling, p53 signalling, inflammation, angiogenesis, and apoptosis. Molecular docking confirmed strong binding affinities of hesperidin and narirutin to the predicted targets.
    CONCLUSION: Anti-proliferative assays, network pharmacology, and molecular docking collectively demonstrate that hesperidin and narirutin from CR show strong therapeutic potential against PCa and BPH. The findings highlight the involvement of AGE-RAGE and p53 signalling pathways and support the potential of these compounds in future drug development.
    Keywords:  Citrus reticulata; benign prostatic hyperplasia; hesperidin; narirutin; network pharmacology.; prostate cancer
    DOI:  https://doi.org/10.2174/0113816128406327251110111652
  13. Front Cell Dev Biol. 2025 ;13 1722674
    A novel protein encoded by circIMP3 promotes prostate cancer progression by regulating alternative splicing and tumor microenvironment.
    Wenren Zuo, Weizhou Huang, Haojie Chen, Yan Xu, Yang Zhang.
       Introduction: Prostate cancer (PC) is one of the most prevalent malignancies in men, with rising incidence and mortality rates globally. Despite advances in therapeutic options such as androgen deprivation therapy and chemotherapy, effective cures, especially for advanced stages of the disease, remain limited. Recent research has highlighted the significant roles of alternative splicing (AS) and noncoding RNAs in tumor progression and drug resistance. This study aims to investigate the role of circIMP3, derived from the IMP3 gene, in prostate cancer development.
    Methods: In this study, we employed quantitative PCR, RNA sequencing, and immunoblotting to identify and characterize circIMP3 in prostate cancer tissues and patient blood samples. Functional assays, including cell proliferation and in vivo tumorigenicity assays, were conducted to assess the biological role of circIMP3 in PC cells. RNA immunoprecipitation sequencing (RIP-seq) was used to identify alternative splicing events regulated by circIMP3. Additionally, exosome isolation and uptake assays were performed to explore the paracrine signaling function of circIMP3 within the tumor microenvironment (TME).
    Results: We identified circIMP3, which is significantly upregulated in both prostate cancer tissues and peripheral blood of patients. CircIMP3 contains an internal ribosome entry site (IRES) and encodes a previously uncharacterized 288-amino-acid protein, circIMP3_288aa. Functional assays revealed that circIMP3_288aa promotes cell proliferation in vitro and accelerates tumor growth in vivo. Mechanistically, circIMP3_ 288aa regulates the alternative splicing of FBXW7, leading to impaired c-Myc ubiquitination and stabilization, which enhances oncogenic signaling. RIP-seq analysis identified over 2,000 alternative splicing events regulated by IMP3, with a notable enrichment in pathways related to ubiquitin-mediated proteolysis. Furthermore, circIMP3 is secreted into the TME via exosomes, where it is taken up by recipient cells, contributing to their proliferation.
    Discussion: Our findings demonstrate that circIMP3 acts as a key regulator of both intracellular alternative splicing and extracellular paracrine signaling within the TME. The ability of circIMP3 to influence FBXW7 splicing and stabilize c-Myc provides a mechanistic basis for its role in promoting oncogenesis in prostate cancer. Clinically, high expression levels of circIMP3 correlate with poorer event-free survival in prostate cancer patients, suggesting its potential as a prognostic biomarker. Additionally, the detection of circIMP3 in peripheral blood positions it as a promising target for liquid biopsy applications in PC diagnosis and monitoring.
    Keywords:  Fbxw7; IMP3; alternative splicing; c-Myc; circular RNA; prostate cancer
    DOI:  https://doi.org/10.3389/fcell.2025.1722674
  14. Front Cell Dev Biol. 2025 ;13 1722671
    The predictive value of necroptosis-related lncRNAs in prostate cancer prognosis and their potential to distinguish between cold and hot tumors.
    Ke Zhang, Kai Li, Junpeng Deng, Chunchun Zhao, Fei Wang, JianJun Xie.
       Background: Prostate cancer (PCa) is frequently associated with poor prognosis, and immunotherapy has shown limited efficacy. This study aimed to identify novel necroptosis-related long non-coding RNAs (lncRNAs) that could predict patient outcomes and guide personalized treatment.
    Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA) were analyzed using co-expression analysis and univariate Cox regression to identify lncRNAs associated with PCa progression. A necroptosis-related lncRNA prognostic model was constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and validated via Kaplan-Meier survival analysis, time-dependent receiver operating characteristic (ROC) curves, Cox regression, and calibration plots. Functional analyses included Gene set enrichment analysis (GSEA), principal component analysis (PCA), immune profiling, and half-maximal inhibitory concentration (IC50) predictions to explore therapeutic implications.
    Results: We established a nine-lncRNA necroptosis-related signature with strong prognostic performance. Among these, NR2F1-AS1 was identified as a core oncogenic lncRNA, showing marked upregulation in PCa tissues and promoting proliferation, invasion, and migration in vitro. The two inferred risk groups demonstrated distinct immune characteristics: hot tumors (Cluster 2) exhibited higher infiltration of activated immune cells, increased immune checkpoint expression, and greater predicted sensitivity to immunotherapy, whereas cold tumors showed immunosuppressive infiltration patterns and lower checkpoint levels. These features allowed the model to robustly distinguish cold from hot tumor phenotypes.
    Conclusion: Necroptosis-related lncRNAs, particularly NR2F1-AS1, may serve as prognostic biomarkers and inform immune-based stratification, supporting more precise personalized treatment strategies for PCa.
    Keywords:  cold-hot tumors; immune profiling; immunotherapy; necroptosis; prostate adenocarcinoma
    DOI:  https://doi.org/10.3389/fcell.2025.1722671
  15. Front Immunol. 2025 ;16 1637325
    Identify GDPD3 as a key regulator of epithelial-mesenchymal transition and prostate adenocarcinoma progression via the LPA/LPAR1/AKT axis: transcriptomic and experimental study.
    Lin Hao, Xiangqiu Chen, Tao He, Tao Wu, Zhiqiang Wen, Ziliang Ji, Xichun Zheng, Qingyou Zheng, Qingchun Zhou, Chengwu He, Qishan Long, Donglin Sun.
       Background: Prostate adenocarcinoma (PRAD) is a common malignancy with marked clinical heterogeneity, complicating prognosis and disease monitoring. Traditional tools like the Gleason score lack molecular and microenvironmental insights, underscoring the need for biomarker-driven predictive models.
    Methods: Single-cell RNA-seq data from GEO and bulk RNA-seq data from TCGA were analyzed. scRNA-seq processing used the Seurat package, with cluster-specific genes identified via FindAllMarkers. Differentially expressed genes (DEGs) from bulk data were obtained using limma, and key gene modules were identified through WGCNA. Using univariate Cox regression and LASSO analysis, a prognostic model was developed based on cluster-specific genes, key module genes, and differentially expressed genes. Clinical validation included comparison of tumor and adjacent normal tissues, revealing significantly elevated GDPD3 expression, further confirmed by immunohistochemistry. In vitro knockdown experiments were conducted in DU145 cells to assess GDPD3's role in promoting proliferation, migration, and epithelial-mesenchymal transition (EMT).
    Results: In this study, through integrated single-cell sequencing and Bulk-RNA-seq analyses, we established a 21-gene prognostic model. QPCR confirmed significant upregulation of three candidates, including GDPD3, which was also elevatedin malignant tissues. Knockdown of GDPD3 inhibited tumor cell proliferation, invasion, and migration. Mechanistically, GDPD3 regulated the levels of lysophosphatidic acid (LPA), which in turn induced EMT in tumor cells. Inhibition or knockdown of the LPA receptor LPAR1 suppressed EMT. LPA promoted EMT through activation of the AKT signaling pathway, and inhibition of this pathway reversed LPA-induced EMT.
    Conclusion: This study underscores key molecular mechanisms underlying prostate cancer progression, with GDPD3 emerging as a potential therapeutic target.
    Keywords:  GDPD3; epithelial–mesenchymal transition; prognosis; prostate adenocarcinoma; transcriptomic analysis
    DOI:  https://doi.org/10.3389/fimmu.2025.1637325
  16. Adv Sci (Weinh). 2026 Jan 21. e18582
    Microenvironment-Guided Evolution of ssDNA-SWCNT Probes for Selective Recognition of Aggressive Prostate Cancer Phenotypes.
    Dakyeon Lee, Seok-Hyeon Lee, Yunseo Jung, Jeongho Lee, Min-Seo Choi, SaeOck Oh, Sungjee Kim, Byoung Soo Kim, Sanghwa Jeong.
      Despite advances in prostate cancer detection, distinguishing indolent from aggressive phenotypes remains challenging. We report a microenvironment-guided strategy for evolving phenotype-specific molecular probes using single-stranded DNA-functionalized single-walled carbon nanotubes (ssDNA-SWCNTs). Our approach employs 3D tumor models that recapitulate complex cancer microenvironments, enabling identification of ssDNA sequences with differential binding properties. We developed two distinct probes for prostate cancer cells: PC3D2, which preferentially binds hypoxia-adapted stem-like cells associated with treatment resistance, and PC2D2, which shows enhanced binding to mesenchymal-like cells. These probes exhibit characteristic second near-infrared (NIR-II, 1000-1700 nm) fluorescence, enabling non-invasive detection of aggressive phenotypes in heterogeneous tumors using NIR-II optical imaging. We demonstrate their utility for selective drug delivery to prostate cancer spheroids, resulting in enhanced therapeutic efficacy. This platform represents a significant advancement in precision diagnostics and theranostics, potentially transforming prostate cancer management through phenotype-specific targeting. The methodology offers a generalizable approach for developing nanoprobes that recognize clinically relevant cancer phenotypes based on their unique microenvironmental signatures rather than individual biomarkers.
    Keywords:  3D bioprinting; DNA; SELEX; carbon nanotube; prostate cancer
    DOI:  https://doi.org/10.1002/advs.202518582
  17. ACS Omega. 2026 Jan 13. 11(1): 1557-1574
    Integrating Proteomics and Predictive Model: Elucidating the Role of Aminated Nanodiamonds in Suppressing Prostate Cancer Growth.
    Wenjie Xie, Qianfeng Xu, Zeheng Tan, Jundong Lin, Fen Zou, Muqi Chen, Jiaquan Xu, Guowei Zhong, Qiuling Du, Jinxiang Zhang, Jibiao Li, Minyao Jiang, Ming Xi, Wei Hua, Yangjia Zhuo, Yixun Zhang, Qishan Dai, Weide Zhong.
      Prostate cancer (PCa) presents a formidable therapeutic challenge owing to the limited efficacy of existing treatments. In this study, a series of comparative experiments demonstrated that nanodiamonds (NDs) with different functional groups exhibit inhibitory effects on the growth, replication, and migration of prostate cancer cells without directly killing the cells. Among them, aminated nanodiamonds (aNDs) showed the most pronounced inhibitory activity. Subsequently, a combination of proteomics analysis and machine learning was employed to elucidate the molecular mechanisms by which these aNDs exerted their inhibitory effects on PCa progression. Data-independent acquisition proteomics identified the key proteins affected by the aNDs, and the Kyoto Encyclopedia of Genes and Genomes analysis revealed ribosome pathway enrichment. Bioinformatics analysis focused on ten crucial genes, thus incorporating a novel prognostic model that categorized patients based on gene expression and emphasized the significance of mitochondrial ribosomal protein L22 (MRPL22). In vivo experiments confirmed the antitumor effects and biocompatibility of the aNDs. In addition, an analysis of the response of MRPL22 to anticancer drugs in public databases revealed its relevance to a range of drugs and compounds. In summary, this study integrated diverse interdisciplinary methodologies, thereby offering insights into the mechanism of the inhibition of PCa by the aNDs and the regulatory role of MRPL22 in the ribosomal pathway.
    DOI:  https://doi.org/10.1021/acsomega.5c09311
  18. Cureus. 2025 Dec;17(12): e99640
    Inflammation Beyond the Prostate: The Role of Systemic Inflammatory Disorders in Prostate Carcinogenesis.
    Gurjit K Bhatti, Ishtiaq Ahmed, Anushka Verma, Inderpal S Sidhu, Jasvinder S Bhatti, Kawaljit S Kaura.
      Prostate cancer remains the most frequently diagnosed malignancy in men worldwide, yet the mechanisms driving its pathogenesis extend far beyond organ-specific factors confined to prostatic tissue. Emerging evidence increasingly demonstrates that systemic inflammatory disorders and body-wide inflammatory processes function as fundamental drivers of prostate cancer initiation and progression. This comprehensive review examines the multifaceted mechanisms by which systemic inflammation contributes to prostate carcinogenesis, synthesizing evidence from diverse inflammatory disease contexts, including obesity, rheumatoid arthritis, systemic autoimmune diseases, cardiovascular disease, and chronic kidney disease. Systemic inflammatory biomarkers, including C-reactive protein, composite inflammatory indices such as the systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio, provide accessible measures of systemic inflammatory burden with significant prognostic utility in prostate cancer prediction and outcome assessment. Multiple molecular mechanisms interconnect systemic inflammation with prostate carcinogenesis - pro-inflammatory cytokines act as endocrine signals activating proliferative pathways in prostate epithelial cells; systemic inflammation promotes recruitment of pro-tumor myeloid-derived cells; oxidative stress generates DNA damage, increasing mutation frequency; inflammatory mediators facilitate angiogenesis and vascular permeability; and chronic immune activation impairs regulatory T cell differentiation while promoting immunosuppression. Recognition of systemic inflammation as a central driver of prostate cancer opens therapeutic opportunities through lifestyle modifications that reduce the systemic inflammatory burden, pharmacologic targeting of inflammatory pathways, and the integration of inflammatory biomarkers into clinical risk stratification and treatment planning algorithms. These integrated approaches may simultaneously optimize prostate cancer outcomes while addressing cardiovascular and metabolic comorbidities, sharing common inflammatory drivers.
    Keywords:  adipokines; carcinogenesis; inflammatory biomarkers; obesity; prostate cancer; systemic inflammation
    DOI:  https://doi.org/10.7759/cureus.99640
  19. Int J Surg. 2026 Jan 19.
    Inhibition of LONP1 in prostate cancer: bibliometrics-guided target screening and AI-driven antibody design.
    Jiawei Pan, Yuan Zhang, Anqi Yang, Linglong Jiang, Yuwei Shen, Yangyang Sun, Jundong Zhu, Zhen Chen, Min Fan, Jian Shi.
       BACKGROUND: Prostate cancer remains one of the most common malignant tumors among men worldwide, with its incidence showing a continuous global increase. In recent years, mitochondria-targeted therapeutic strategies have emerged as a prominent research focus in oncology. However, a systematic analysis of the research trends concerning mitochondria in prostate cancer treatment is currently lacking. This study employed bibliometric methods to conduct a comprehensive analysis of the dynamic progress in mitochondria-related prostate cancer research, ascertain its significant role, and identify potential mitochondria-targeted therapeutic targets. Furthermore, using computer-aided methods, we designed and optimized a specific antibody, providing a candidate strategy for prostate cancer control.
    METHODS: This study utilized the Web of Science Core Collection database (2015-2023) to perform visual analysis of country-keyword network relationships using CiteSpace and the Bibliometric Online Analysis Platform. Target screening was conducted by integrating bioinformatics and research intelligent agents. Subsequently, inhibitory antibodies were designed and screened based on GeoBiologics, followed by systematic in vitro evaluation of their purity, antigen-antibody affinity, conformational stability, colloidal stability, and enzymatic inhibitory activity.
    RESULTS: The role of mitochondria in prostate cancer has garnered significant attention. Research trends have shifted from fundamental mechanisms to addressing drug resistance, developing novel delivery systems, and exploring combination therapies, highlighting mitochondria as a promising target for clinical intervention. Lon Peptidase 1(LONP1) is closely associated with mitochondrial homeostasis and prostate cancer progression. Antibody_82-M1 effectively blocks the ATP-binding site of LONP1, demonstrating high affinity, favorable stability, a high degree of humanization, and excellent drug-like properties, indicating strong potential for clinical translation.
    CONCLUSION: The designed LONP1 inhibitory antibody offers a novel strategy for prostate cancer treatment. The proposed workflow - "bibliometric guidance - research intelligent agent screening - bioinformatics support" - proves beneficial for enhancing AI-driven scientific research and optimizing the screening of therapeutic targets for diseases.
    Keywords:  GeoBiologics; LONP1; bibliometric; mitochondria; prostate cancer
    DOI:  https://doi.org/10.1097/JS9.0000000000004705
  20. Front Immunol. 2025 ;16 1709264
    Identification of prognostic biomarkers and development of a prediction model for prostate cancer.
    Dake Chen, Wu Chen, Ruxian Ye, Linjin Li, Feilong Miao, Xianghui Kong, Weiqiang Ning, Jingyi Jia, Qiuli Chen, Peter Wang, Bowei Yin.
       Background: Prostate cancer (PCa) is biologically heterogeneous, and its molecular underpinnings remain incompletely define. In this study, we sought to identify genes shared between PCa cells and stem-like subpopulations and to develop a prognostic model.
    Methods: RNA sequencing was performed on PC3 cells and side population stem-like cells (SPC). Primary prostate tumor data were obtained from GSE172301, and The Cancer Genome Atlas (TCGA) provided transcriptomes with clinical annotations. Differential expression, immune microenvironment and infiltration analyses were conducted. Single-cell spatiotemporal transcriptomics data were analyzed using Seurat and spatialLibs. To delineate the role of PLXNA4 in PCa cells, we performed CCK-8 viability assays, EdU incorporation assays, Annexin V-FITC/PI flow cytometry for apoptosis, and Matrigel-coated Transwell invasion assays.
    Results: We identified 562 upregulated and 671 downregulated genes in SPC. A total of nine genes emerged, including CPNE6, RASL10B, GCNT4, STAC2, RBPMS2, PADI3, PLXNA4, S100A14, and MMP9, as potential targets using the support vector machine (SVM) and LASSO methods, with MMP9 highly expressed in tumor cells. A three-gene prognostic signature (RASL10B, RBPMS2, ANGPTL3) stratified patients into risk groups. The high-risk group showed enrichment of Gene Ontology terms related to immune activation, antigen receptor signaling, and B-cell-mediated immunity. We also cataloged seven ubiquitin-related markers and putative ubiquitination sites. Functionally, PLXNA4 depletion reduced cell viability and proliferation, increased apoptosis, and suppressed invasion in PCa cells.
    Conclusions: We identified nine target genes and propose a three-gene prognostic model for outcome prediction in PCa. Our findings suggest that targeting PLXNA4 may offer new therapeutic opportunities for the treatment of PCa, including immunotherapy.
    Keywords:  PC3; immunotherapy; learning machine; prostate cancer; stem cells
    DOI:  https://doi.org/10.3389/fimmu.2025.1709264
  21. Cancer Sci. 2026 Jan 19.
    Compound Library Screening Identified Cladribine as a Novel Radiosensitizer for Prostate Cancer.
    Toshiki Oka, Koji Hatano, Shohei Katsuki, Tomohiro Kanaki, Shunsuke Inoguchi, Masaru Tani, Akihiro Yoshimura, Yuki Horibe, Yutong Liu, Nesrine Sassi, Yohei Okuda, Akinaru Yamamoto, Toshihiro Uemura, Gaku Yamamichi, Yu Ishizuya, Takuji Hayashi, Yoshiyuki Yamamoto, Taigo Kato, Atsunari Kawashima, Keisuke Tamari, Bangzhong Lin, Akiyoshi Tani, Kazutake Tsujikawa, Yutaka Takahashi, Kazuhiko Ogawa, Shawn E Lupold, Norio Nonomura.
      Radiation therapy effectively treats prostate cancer, but tumor recurrence remains a clinical challenge, highlighting the need for strategies to enhance radiosensitivity. In this study, we developed a simple, high-throughput drug repurposing screening platform to find radiosensitizers from compounds approved by the U.S. Food and Drug Administration. A library of 1134 compounds was systematically screened at two concentrations (0.2 and 2 μM) using LNCaP cells stably expressing Metridia luciferase, allowing highly sensitive and quantitative assessment of cell viability through luciferase activity in culture supernatants. In the primary screening, 8 and 12 candidate radiosensitizers were identified at 0.2 μM and 2 μM, respectively. In the secondary screening, 19 compounds were evaluated at two radiation doses (4 Gy and 6 Gy) and six drug concentrations, identifying 5 radiation-sensitizing candidate compounds. Through this stepwise screening approach, cladribine was identified as the most potent radiosensitizer. Cladribine increased radiation-induced cytotoxicity in multiple prostate cancer cell lines (22Rv1, DU145, and PC3), with dose-modifying factors of 1.46, 1.55, and 1.43, respectively, based on the radiation dose needed to achieve 90% cell death. Mechanistically, cladribine prevented the repair of radiation-induced DNA double-strand breaks, shown by increased γH2AX levels. Importantly, its radiosensitizing effect was further confirmed in vivo using 22Rv1 and DU145 xenograft models. This study demonstrates that a luciferase-based high-throughput drug repurposing platform is useful for identifying clinically relevant radiosensitizers, revealing that cladribine is a promising candidate for further translational research in prostate cancer radiotherapy.
    Keywords:  cladribine; compound library screening; prostate cancer; radiation; radiosensitizer
    DOI:  https://doi.org/10.1111/cas.70326
  22. Front Oncol. 2025 ;15 1743689
    The role of neuroendocrine differentiation in treatment resistance of prostate cancer and intervention strategies.
    Baozhen Wang, Yanyun Zhang, Wenbo Zhang.
      Prostate cancer is one of the most common malignancies in men, and resistance to conventional treatments is frequently encountered in clinical practice. Among the mechanisms contributing to this resistance, neuroendocrine differentiation (NED) is particularly significant. NED does not only change the basic biological characteristics of cancer cells but also is capable of inducing resistance to endocrine therapy and chemotherapy, which impact the overall prognosis negatively. While NED drives prostate cancer progression and treatment resistance, its pathophysiology and the mechanisms underlying its development are still poorly understood, which restricts the availability of effective clinical interventions. Hence, a detailed study on the molecular pathways that cause NED and the role of this phenomenon in therapy resistance will be needed to improve treatment outcomes in prostate cancer. This review delineates the role of NED in mediating therapy resistance in prostate cancer and evaluates current therapeutic interventions, with the aim of informing the development of new treatment strategies for this malignancy.
    Keywords:  CRPC; NEPC; neuroendocrine differentiation; prostate cancer; resistance
    DOI:  https://doi.org/10.3389/fonc.2025.1743689
  23. Comput Biol Chem. 2026 Jan 12. pii: S1476-9271(26)00023-X. [Epub ahead of print]122 108898
    Boolean network-based identification of optimal drug combinations for prostate cancer.
    Pranabesh Bhattacharjee, Addanki Pratap Kumar, Aniruddha Datta.
      Prostate cancer is one of the most common cancers among men in the United States and is a leading cause of cancer-related deaths and the second most common cancer in men worldwide. In this study, we used a Boolean network model to analyze prostate cancer signaling pathways and to identify optimal drug combinations for precision therapy. By integrating publicly available biological signaling pathway data with recent research findings, we developed a comprehensive model that represents protein-protein interactions, gene mutations, and pathway dysregulation. Faults induced by mutations were modeled using the "stuck at 0" or "stuck at 1" fault paradigms, capturing the impact of genetic alterations on pathway behavior. The model was simulated across various drug combinations to determine which therapies could most effectively alleviate the aberrant signaling caused by specific mutations. To quantify therapeutic efficacy, we calculated a Size Difference (SD) score, a metric analogous to Hamming distance, measuring the deviation from normal, for each drug combination and fault scenario. The results revealed that drug combinations involving Berberine, Docetaxel, Olaparib, and Enzalutamide showed promising prediction efficacy (more than 90 %), indicating higher therapeutic potential. A distinguishing feature of this work is that, in addition to the standard prostate cancer drugs, we have included Berberine, a non-toxic natural compound with beneficial effects. These computational findings provide a framework for future experimental and clinical validation, which is necessary to confirm the therapeutic relevance of the predicted drug combinations.
    Keywords:  Berberine; Boolean modeling; Combination therapy; Enzalutamide; Gene regulatory networks; Prostate cancer; Targeted therapy
    DOI:  https://doi.org/10.1016/j.compbiolchem.2026.108898
  24. Biomater Sci. 2026 Jan 21.
    Combination prostate cancer therapy via CuTCPP-MOF-mediated chemodynamic and photodynamic effects.
    Yu Cao, Cheng Cao, Yingao Jiao, Huifang Hao, Dengyao Gao, Yan Gao, Kunhou Yao, Ruiyi Wu, Yanlei Liu.
      Prostate cancer remains one of the most common malignant tumors among men worldwide, and treatment options are limited in the advanced stage. To address this challenge, we have developed a pH-responsive copper porphyrin metal-organic framework (CuTCPP-MOF), which integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT). It enables efficient electron transfer and ROS generation. Under 488 nm laser irradiation, MOF acts as a self-sensitizing photosensitizer to generate single-state oxygen (1O2), which gradually releases Cu2+ in an acidic environment. Subsequently, it is reduced to Cu+ by intracellular glutathione (GSH), achieving continuous consumption of GSH and enhancing the Fenton-like reaction to promote the continuous formation of hydroxyl radicals (˙OH). This amplifies the oxidative stress within tumor cells. In vitro experiments have shown that ROS accumulation and mitochondrial membrane depolarization lead to apoptosis of RM-1 prostate cancer cells. In vivo, CuTCPP-MOF combined with laser irradiation can significantly inhibit tumor growth without causing systemic toxicity and hemolysis. Histological analysis confirmed that after treatment, the apoptosis of tumor cells was enhanced and their proliferation ability was reduced. In conclusion, CuTCPP-MOF is a promising nano-therapeutic agent that can work in synergy with PDT and CDT to achieve effective and safe treatment of prostate cancer.
    DOI:  https://doi.org/10.1039/d5bm01627d
  25. Cell Signal. 2026 Jan 16. pii: S0898-6568(26)00016-1. [Epub ahead of print]141 112367
    Cellular signaling and radioresistance in prostate cancer.
    Gustavo A Sosa, Betsy Crosswhite, Austin N Kirschner.
      
    Keywords:  Androgen receptor; DNA damage repair; Hypoxia; Prostate cancer; Radioresistance; Radiotherapy; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.cellsig.2026.112367
  26. Eur J Cancer Prev. 2026 Jan 21.
    Fat quality, not quantity, linked to reduced risk of advanced and lethal prostate cancer in US populations: a large prospective multicenter study.
    Yadong Li, Manli Zhou, Yuanpeng Liao, Qiliang Zhai, Kaidi Zhang, Xin Huang, Mayao Luo, Shidong Lv, Qiang Wei.
       BACKGROUND: Epidemiological evidence on dietary fat intake and advanced prostate cancer (PCa) risk is limited and inconclusive; moreover, no prospective study has been conducted to investigate the association between fat quality and quantity and advanced and lethal PCa risk.
    METHODS: This prospective cohort included 49 424 men from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The fat quality index (FQI) and low-fat diet score (LFDs) were used to evaluate the quality and quantity separately, where higher scores indicated greater adherence. Cox proportional hazards regression was used to evaluate the risk of PCa incidence and mortality. Subgroup analyses were conducted to identify potential confounders. Sensitivity analyses were performed to assess the robustness of the results.
    RESULTS: During follow-up, a total of 857 incident cases of advanced PCa, including 425 lethal PCa were documented. Individuals in the highest compared with the lowest quartiles of FQI had a lower advanced PCa [hazard ratioQ4 versus Q1 : 0.72, 95% confidence interval (CI): 0.58-0.88, P for trend = 0.002] and lethal PCa (hazard ratioQ4 versus Q1 : 0.65, 95% CI: 0.48-0.87, P for trend = 0.005). This inverse association between FQI and advanced PCa risk was not observed for nonlethal PCa. Subgroup analyses indicated this inverse association of FQI with advanced PCa was only observed in participants with higher LFDs. No significant associations were found between LFDs and the risk of advanced and lethal PCa.
    CONCLUSION: Our findings suggest focusing on higher quality, rather than restricting the quantity of fat intake, may be an effective approach to reduce the risk of advanced PCa in the US population, particularly for lethal PCa.
    Keywords:  advanced prostate cancer; cancer prevention; epidemiology; fat quality index; low-fat diet pattern
    DOI:  https://doi.org/10.1097/CEJ.0000000000001007
  27. Tohoku J Exp Med. 2026 Jan 22.
    Long Noncoding RNA ST8SIA6-AS1 Promotes the Development of Prostate Cancer by Activating the TGF-β/Smad Signaling Pathway through Regulating the miR-18a-5p/TGFBR1 Axis.
    Qingshan Liu, Jian Ke, Yu Luo.
      
    DOI:  https://doi.org/10.1620/tjem.2025.J140
  28. Biochim Biophys Acta Rev Cancer. 2026 Jan 16. pii: S0304-419X(26)00009-0. [Epub ahead of print]1881(2): 189537
    Targeting glycolysis in prostate cancer: Molecular mechanisms and therapeutic advances.
    Jiexiang Zhang, Tongtong Zhang, Dexin Song, Dongliang Xu.
      Prostate cancer (PCa) is the second most common cancer among men worldwide and poses a significant threat to male health. A key feature of tumor progression is metabolic reprogramming, which involves the abnormal activation of glycolysis. This metabolic process supports PCa proliferation, metastasis, and drug resistance through rapid energy production, the provision of biosynthetic precursors, and the remodeling of the tumor microenvironment (TME). Key enzymes such as hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase M2 (PKM2), glucose transporters (GLUTs), and lactate dehydrogenase A (LDHA) play pivotal roles in regulating aerobic glycolysis in PCa cells. Glycolytic enzymes are modulated by a variety of mechanisms, including the PI3K/AKT and AMPK signaling pathways, hypoxia-inducible factor 1α (HIF-1α), c-Myc, and non-coding RNAs. Current therapeutic strategies targeting glycolysis include natural products and small-molecule inhibitors. Targeting glycolysis presents novel opportunities to address existing limitations in PCa management. This review discusses the advances, challenges, and future research directions in glycolysis-focused PCa studies, providing a theoretical foundation for the development of precise metabolic interventions.
    Keywords:  Glycolysis; Metabolic reprogramming; Molecular mechanism; Prostate cancer; Therapeutic advance; Warburg effect
    DOI:  https://doi.org/10.1016/j.bbcan.2026.189537
  29. iScience. 2026 Jan 16. 29(1): 114552
    Combined prostate cancer vaccine plus immune checkpoint inhibition synergizes to eliminate prostate cancer.
    Gabriel Carreno-Galeano, Seema Dubey, Kenneth A Iczkowski, Peter Van Veldhuizen, Uzoma A Anele, Jamie C Messer, Murali K Ankem, Dev Karan.
      Immunotherapy has improved outcomes in many cancers, yet the clinical benefits remain limited in prostate cancer. We evaluated whether an adenovirus-based bivalent prostate cancer vaccine (Ad-PS2) targeting two tumor antigens could be strengthened by combination with immune checkpoint blockade. Using immunocompetent mouse models, we found that Ad-PS2 combined with low-dose anti-CTLA4 generated robust anti-tumor immunity capable of eliminating established tumors, exceeding the effects of either treatment alone. Tumor-free mice resisted subsequent tumor rechallenge, indicating durable immune protection. Tumor analysis revealed a significant increase in intratumor CD8+ T cell infiltration with Ad-PS2 and anti-CTLA4, whereas anti-PD1 alone produced minimal infiltration and, with the vaccine, provided no therapeutic advantage. These results highlight a mechanistically synergistic interaction between dual antigen-targeted vaccination and CTLA4 blockade and illustrate how rational combination immunotherapy can overcome resistance in prostate cancer. This work defines a strategy that could inform future translational approaches for improving immunologic control of prostate cancer.
    Keywords:  Biotechnology; Cancer; Immunology
    DOI:  https://doi.org/10.1016/j.isci.2025.114552
  30. Expert Opin Drug Deliv. 2026 Jan 22. 1-16
    Clinical hurdles for curcumin and piperine nanoparticles in prostate cancer treatment: a bridge too far or a path to clinical reality?
    Jibira Yakubu, Oya Tagit, Amit V Pandey.
       INTRODUCTION: Prostate cancer (PC) treatment is limited by resistance mechanisms and cumulative toxicities, necessitating novel therapeutic strategies. While curcumin and piperine exhibit potent anticancer properties, their clinical utility is severely compromised by poor bioavailability and rapid metabolism.
    AREAS COVERED: This review critically analyzes the preclinical and clinical landscape of curcumin and piperine nanoformulations (CPN) for the treatment of PC. We utilized PubMed and Scopus (2000-2025) to evaluate molecular mechanisms, focusing on CYP17A1 inhibition, PI3K/Akt/mTOR signaling, and ferroptosis. The report examines the physicochemical properties of nanocarriers, including PLGA and liposomes, and addresses translational barriers such as the heterogeneity of the Enhanced Permeability and Retention (EPR) effect, stromal density, and risks associated with piperine-mediated drug - drug interactions.
    EXPERT OPINION: While nano-encapsulation enhances the therapeutic index of curcumin, clinical translation remains stalled by a reliance on passive targeting and insufficient manufacturing scalability. Future success depends on shifting from 'beaker' synthesis to microfluidic production (Quality by Design) and adopting active targeting (e.g. PSMA-directed delivery) to penetrate the prostate stroma. Without these strategic pivots and biomarker-driven trials, CPNs risk remaining an academic curiosity rather than evolving into a viable clinical intervention.
    Keywords:  CYP17A1; Steroidogenesis; androgen synthesis; curcumin nanoparticles; nanoparticle formulations; prostate cancer
    DOI:  https://doi.org/10.1080/17425247.2026.2619094
  31. Eur Urol Open Sci. 2026 Feb;84 40-49
    Diversity of Gut Microbiota and Metabolites in Benign Prostatic Hyperplasia with Different Prostate Volumes.
    Jiayi Liu, Yuanming Chen, Yong Wang, Deng Li, Zijie Xu, Jianong Zhang, Liang Qin, Bangmin Han, Yifeng Jing, Di Cui, Yiping Zhu, Shujie Xia, Chenyi Jiang.
       Background and objective: The gut microbiota, influenced by age and sex hormones, may correlate with the development and progression of benign prostatic hyperplasia (BPH). This study aims to characterize gut microbiota and metabolite profiles in BPH patients with varying prostate volumes.
    Methods: Fecal samples from BPH patients were analyzed using 16S rDNA sequencing and untargeted metabolomics. Microbial and metabolic differences were assessed via the Linear discriminant analysis Effect Size, KEGG pathway enrichment, and a mediation analysis.
    Key findings and limitations: We identified 26 differential amplicon sequence variants (ASVs) and 70 metabolites, with 18 microbes correlating significantly with clinical BPH indicators. The key pathways included unsaturated fatty acid and steroid hormone biosynthesis. Akkermansia (ASV549) may affect prostate volume through the regulation of intestinal amino acid metabolism and may negatively affect prostate-specific antigen levels by inhibiting heat shock protein (HSP) 90 (luminespib). Limitations include sample size and unmeasured confounders.
    Conclusions and clinical implications: Gut microbiota and metabolite diversity are associated with prostate volume; further studies are warranted to elucidate the potential interventions via microbiome modulation or metabolic targeting for BPH management.
    Patient summary: In this study, we identified the potential associations between gut and both prostate volume and benign prostatic hyperplasia symptoms. These findings suggest that dietary interventions or fecal microbiota transplantation may represent potential strategies for modulating prostate health in the future.
    Keywords:  Benign prostatic hyperplasia; Gut metabolites; Gut microbiota; Prostate volume
    DOI:  https://doi.org/10.1016/j.euros.2025.12.016
  32. Eur J Med Chem. 2026 Jan 13. pii: S0223-5234(26)00028-0. [Epub ahead of print]305 118583
    Current landscape and therapeutic prospects of indole hybrids for prostate cancer treatment: A mini-review.
    Zhi Xu, Yang Shi, Bowen Pan, Huabin Wang.
      Prostate cancer ranks second in incidence and fifth in mortality among all cancer types in males. This striking epidemiological profile highlights its status as a major health concern that poses a severe threat to men's lives and health globally. Although traditional chemotherapeutics and targeted therapies for prostate cancer have made considerable progress, critical challenges remain, including high metastatic potential, acquired drug resistance, and unfavorable prognosis in patients with advanced disease, highlighting the imperative to develop novel therapeutic strategies. Indole hybrids, versatile and promising anticancer scaffolds formed by integrating indole moieties with other pharmacophores, exhibit prominent multi-targeted regulatory capabilities in prostate cancer therapy, enabling simultaneous modulation of key oncogenic pathways to address the complex molecular mechanisms of both hormone-sensitive and castration-resistant subtypes. Compared to single-scaffold derivatives, indole hybrids demonstrate enhanced anticancer potency and reduced off-target toxicity via synergistic effects between conjugated moieties, while also showing potential in overcoming drug resistance by circumventing single-target mutation-induced resistance and inhibiting ABC transporters to reverse multidrug resistance. Moreover, their structural flexibility facilitates structural optimization for improved pharmacokinetic properties and tailored efficacy against specific prostate cancer phenotypes, making indole hybrids valuable candidates for developing novel therapeutic agents to meet unmet clinical needs in prostate cancer treatment. This review summarizes the recent advances in indole hybrids with anti-prostate cancer activity from 2021 to date, striving to open new directions for developing novel prostate cancer therapeutics.
    Keywords:  Hybrids; Indole; Mechanisms of action; Prostate cancer; Structure-activity relationships
    DOI:  https://doi.org/10.1016/j.ejmech.2026.118583
  33. Eur J Med Chem. 2026 Jan 09. pii: S0223-5234(26)00016-4. [Epub ahead of print]306 118571
    Multi-stimuli activated PROTAC prodrug for controlled protein degradation with enhanced therapeutic effects.
    Tianyang Zhou, Yibo Gao, Bohan Ma, Chi Wang, Shan Xu, Xiaoyu Feng, Bin Wang, Yanlin Jian, Lei Li.
      Proteolysis-targeting chimeras (PROTACs) have emerged as a transformative strategy for targeted protein degradation, yet their clinical translation is hindered by systemic toxicity and poor tumor selectivity, leading to dose-limiting side effects. To overcome these limitations, we designed a multi-stimuli-responsive prodrug that enables tumor-selective activation of PROTACs in response to elevated reactive oxygen species (ROS) and glutathione (GSH) in the tumor microenvironment. By masking the hydroxyl group of the VHL ligand with a ROS/GSH-cleavable thioether-urea linker, we developed a PROTAC prodrug that responds to 1O2, HOCl, H2O2, and GSH-key mediators of oxidative stress in tumors. This proof-of-concept was verified by caging BRD4 and AR PROTAC with a methylene blue fluorophore to yield NZ-BRD and NZ-AR. Upon encountering tumor-associated stimuli, these prodrugs underwent efficient activation, releasing functional PROTACs that selectively degraded BRD4 and AR in prostate cancer cells. Intriguingly, the methylene blue liberated during activation served as a self-amplifying photosensitizer, creating a positive feedback loop that boosted 1O2 generation and further enhanced prodrug cleavage. The synergistic effect between PROTAC-mediated protein degradation and photodynamic therapy led to superior antitumor efficacy of PROTAC prodrugs in vitro and in vivo. Our work establishes a spatiotemporally controlled drug activation paradigm that combines precision protein degradation with ROS-amplified activation, presenting a promising approach to mitigate the systemic toxicity associated with conventional PROTAC therapy.
    Keywords:  PROTAC; Photodynamic therapy; Prodrug; Reactive oxygen species (ROS)
    DOI:  https://doi.org/10.1016/j.ejmech.2026.118571
  34. Comb Chem High Throughput Screen. 2026 Jan 09.
    Identification of a Cuproptosis-Related Molecular Signature for Predicting Biochemical Recurrence in Prostate Cancer.
    Dong-Ning Chen, Xiao-Hui Wu, Qi You, Rui-Bin Zhuang, Zhong-Tian Ruan, Jun-Ming Zhu, Qing-Shui Zheng, Ye-Hui Chen, Yong Wei, Xiao-Dan Lin, Xue-Yi Xue.
       BACKGROUND: This study aimed to develop and validate a Cuproptosis-Related Gene (CRG) signature for predicting Biochemical Recurrence-Free Survival (BCRFS) and characterizing the Tumor Immune Microenvironment (TIME) in Prostate Cancer (PCa).
    METHODS: Transcriptomic and clinical data were collected from TCGA (n=405) and GEO (GSE70770, n=203). Consensus clustering based on 10 CRGs defined molecular subtypes. Differentially expressed genes between clusters were subjected to LASSO Cox regression to construct a prognostic signature in the TCGA cohort, followed by validation in GEO and combined cohorts. Quantitative real-time polymerase chain reaction (qRT-PCR) and Immunohistochemistry (IHC) were conducted for experimental validation.
    RESULTS: Two CRG-based subtypes were identified, characterized by distinct clinicopathological features, immune checkpoint expression, and BCRFS. A six-gene signature (CALML5, MMP11, UBE2C, ANPEP, TMEM59L, COMP) stratified patients into high- and low-risk groups with significantly different BCRFS (log-rank P<0.001). The model showed good predictive accuracy (AUCs 0.717-0.837 at 1 year, 0.728-0.771 at 3 years, 0.683-0.695 at 5 years) and remained independent of clinicopathological factors. High-risk patients exhibited elevated immune/stromal scores, altered immune infiltration, and higher immune checkpoint expression. qRT-PCR confirmed upregulation of CALML5, MMP11, UBE2C, and COMP in PCa cell lines, while IHC validated differential protein expression of all six genes between PCa and BPH tissues (all P<0.05).
    DISCUSSION: This six-gene CRG signature predicts BCRFS and reflects immune heterogeneity in PCa. Its integration into prognostic models may guide personalized management and inform immunotherapy strategies, warranting further validation in prospective clinical studies.
    CONCLUSION: This study initially identified two cuproptosis-related molecules based on the expression patterns of cuproptosis-related genes. In addition, we developed a new cuproptosisrelated molecular signature with great predictive performance for BCRFS and tumor immune environment using six DERRGs (including CALML5, MMP11, UBE2C, ANPEP, TMEM59L, COMP). These findings would be conducive to a deeper cognition of the potential mechanism of cuproptosis of PCa.
    Keywords:  Prostate cancer; biochemical recurrence; cuproptosis; molecular signature; nomogram.; tumor immune microenvironment
    DOI:  https://doi.org/10.2174/0113862073412459251117113248
  35. Curr Med Chem. 2026 Jan 09.
    Computational Analysis and in vitro Validation of the Anti-Prostate Cancer Activity of Sesamin from Sesamum indicum.
    Shu-Ming Huang, Cheng-Hung Chuang, Marineil C Gomez, Lemmuel L Tayo, Cheng-Yang Hsieh, Po-Wei Tsai, Hung-Chang Hung.
       INTRODUCTION: Prostate cancer is the fourth most commonly diagnosed cancer worldwide and the eighth leading cause of cancer-related mortality, primarily affecting elderly males. Conventional therapeutic approaches, while effective in some cases, often come with substantial side effects, posing particular challenges for older patients. As a result, the exploration of natural compounds from traditional Chinese medicine (TCM) as potential anticancer agents has gained increasing attention. Sesamin, a dietary lignan found in sesame seeds and frequently used in TCM, has shown promise in preliminary studies for its antioxidant, anti-inflammatory, and potential anticancer properties. However, its specific effects and underlying mechanisms against prostate cancer cells remain inadequately characterized.
    MATERIALS AND METHODS: This study investigated the anticancer effects of sesamin on human prostate cancer DU145 cells. Cell viability was evaluated using MTT assays. Apoptosis induction and cell cycle distribution were assessed by flow cytometry. Protein expression levels of PPAR-γ, p21, and p53 were measured using Western blotting. Additionally, in silico molecular docking was performed using the LibDock algorithm to evaluate sesamin's binding affinity with the target proteins PPAR-γ and p21.
    RESULTS: Sesamin treatment significantly reduced the viability of DU145 cells in a dose-dependent manner. Flow cytometry revealed increased apoptosis and cell cycle arrest at the G1 phase. Western blot analysis showed upregulated expression of PPAR-γ and p21, while p53 expression remained largely unchanged. Molecular docking analysis demonstrated strong binding affinity of sesamin to PPAR-γ (LibDock score: 125.03) and p21 (LibDock score: 105.45), supporting its involvement in a p53-independent apoptotic mechanism.
    DISCUSSION: The study demonstrates that sesamin exerts significant anticancer effects on prostate cancer DU145 cells by inhibiting cell viability, inducing apoptosis, and causing G1 phase cell cycle arrest. The upregulation of PPAR-γ and p21, coupled with unchanged p53 expression, suggests that sesamin may activate a p53-independent pathway, a valuable feature in treating prostate cancers with defective p53 signaling. Molecular docking results corroborate these findings, indicating direct interactions between sesamin and its molecular targets.
    CONCLUSION: Sesamin exhibits promising antiproliferative and pro-apoptotic activities against DU145 prostate cancer cells. Its potential to act as a G1-phase-specific chemotherapeutic agent via a p53-independent mechanism warrants further investigation and development as a natural candidate for prostate cancer therapy.
    Keywords:  Apoptosis; CDKN1; P53; PPI; cyclin-dependent kinase inhibitor; sesamin.
    DOI:  https://doi.org/10.2174/0109298673401248251028114820
  36. ACS Appl Nano Mater. 2025 Jul 18. 8(28): 14158-14169
    Time-Resolved Förster Resonance Energy Transfer Nanoassay Based on CdTe Quantum Dots for Sensitive Detection of Prostate Cancer Antigen 3.
    Catarina S M Martins, Anne Nsubuga, Nour Fayad, Ruifang Su, Thibault Gallavardin, Ihsan Çaha, Niko Hildebrandt, Francis Leonard Deepak, João A V Prior.
      Prostate Cancer Antigen 3 (PCA3) is a long noncoding RNA highly expressed in prostate cancer cells, making it a promising biomarker for noninvasive prostate cancer diagnosis. Simple and rapid detection using nanoprobes can potentially overcome the limitations of traditional diagnostic techniques. Here, we designed, characterized, and applied a DNA-strand displacement assay based on Förster Resonance Energy Transfer (FRET) between terbium (Tb) ions and semiconductor quantum dots (QDs) as a proof-of-concept for sensitive and specific mix-and-measure quantification of a synthetic DNA analogue of PCA3. The assay utilized QDs synthesized through an aqueous one-pot method. The time-resolved (TR) FRET assays achieved a detection limit of 0.65 nmol L-1 by using a SPARK benchtop fluorescence plate reader and 0.32 nmol L-1 by using a KRYPTOR Compact PLUS clinical plate reader. Despite slightly decreased performance, the TR-FRET nanoassay demonstrated reliable quantification of nanomolar PCA3 concentrations also in samples containing up to 50% of serum. These findings underscore the potential of Tb-to-QD FRET assays for rapid clinical prostate cancer diagnostics, offering a promising tool for the early detection of PCA3 in a noninvasive manner.
    Keywords:  PCA3; TR-FRET; diagnostics; lncRNA; quantum dots; terbium
    DOI:  https://doi.org/10.1021/acsanm.5c02176
  37. FASEB J. 2026 Jan 31. 40(2): e71477
    Correction to "FOXS1 Acts as an Oncogene and Induces EMT Through FAK/PI3K/AKT Pathway by Upregulating HILPDA in Prostate Cancer".
      
    DOI:  https://doi.org/10.1096/fj.202600191
  38. Neoplasia. 2026 Jan 21. pii: S1476-5586(25)00147-2. [Epub ahead of print]72 101268
    Polyploid cisplatin-resistant cancer cells have altered nuclear organization and epigenomic status.
    Anna Lk Gonye, Linda Orzolek, Christopher Cherry, Michael Patatanian, Luke V Loftus, Kevin Truskowski, George Butler, Kenneth J Pienta, Sarah R Amend.
      Chemotherapy resistance remains a critical barrier in cancer treatment, partly driven by polyploid cells that survive therapy and contribute to tumor recurrence. Here, we investigated epigenomic and transcriptional changes associated with cisplatin-surviving polyploid cells compared to parental cancer cells in prostate cancer (PC3) and triple-negative breast cancer (MDA-MB-231) cell lines. We observed persistent dysregulation of chromatin compaction and altered nuclear structure in polyploid cells following cisplatin treatment. Genome-wide chromatin accessibility profiling via ATAC-seq revealed significant remodeling, notably decreased promoter accessibility at proliferation-associated loci and increased accessibility of distal regulatory elements linked to inflammation and stress response. RNA-seq analyses demonstrated a coordinated transcriptional shift away from proliferative signatures toward inflammatory and survival pathways, including activation of NFκB, interferon response, and integrated stress response pathways. Importantly, we identified subsets of genes showing concordant changes in promoter accessibility and transcriptional activity, directly linking chromatin remodeling to transcriptional reprogramming. These integrated findings highlight the role of chromatin dynamics and epigenetic plasticity in chemotherapy resistance, demonstrating that widespread chromatin accessibility changes facilitate the transition to a stress-adapted, polyploid cell state. This study provides new insights into the molecular mechanisms supporting cancer cell persistence after chemotherapy.
    Keywords:  Chemotherapy resistance; Chromatin accessibility; Endocycling cancer cells
    DOI:  https://doi.org/10.1016/j.neo.2025.101268
  39. Am J Transl Res. 2025 ;17(12): 9881-9893
    Association between red blood cell distribution width to albumin ratio and prostate specific antigen based on NHANES data.
    Zhe Yang, Meihui Zhang, Lulu Liu, Xiaomei Qiu, Yitong Shi, Nuo Li, Haoyong Ning.
      As the most common cancer in men in the United States, risk factors for prostate cancer (PCa) need to be identified. Serum prostate specific antigen (PSA) levels are used for the screening of prostate cancer due to its association with the disease. Investigations have indicated that the risk of prostate cancer determined based on PSA can be further stratified on the basis of total PSA (tPSA) and f/t PSA. Further, the red blood cell distribution width-to-albumin ratio (RAR) has recently been identified as a novel biomarker for multiple inflammatory diseases. The relationship between RAR and PSA remains unclear. Here, we intended to study the association between RAR and PSA. National Health and Nutrition Examination Surveys (NHANES) represents a cross-sectional observational study within the United States. We obtained clinical data throughout the 2003 - 2010 NHANES study period. In 41,156 NHANES men, we selected 5,992 men aged 40 years or older. Missing data were imputed using multiple imputation. The association between RAR and PSA was assessed using multivariable adjusted linear regression analysis. Variance inflation factor (VIF) values were also calculated to exclude collinearity of independent variables. The association of the threshold effects was assessed using inflection points. The effect of RAR levels on PSA was significant in 5,992 subjects after adjusting the confounders (β = 1.13, 95% CI: 0.59-1.67). The notion of a threshold level was supported by the presence of inflection point at RAR = 3.762. The effect of a 1 unit increase in the RAR was a consistently increasing function of quartile of RAR. For instance, in the highest quartile of RAR, if RAR rises by 1 unit, PSA rises by 1.36 (β = 1.36, 95% CI: 0.90-1.83), suggesting a non-linearity of the two. For example, when RAR is below 3.762, higher RAR levels seem associated with higher PSA levels. This is important for understanding the factors that may play an important role in the occurrence and development of prostate cancer. Future studies must do assessments of prostate cancer incidence within the cohorts described.
    Keywords:  NHANES; PSA; RAR; cross-sectional study
    DOI:  https://doi.org/10.62347/CYCT4046
  40. Int J Biol Macromol. 2026 Jan 16. pii: S0141-8130(26)00229-1. [Epub ahead of print]341(Pt 2): 150303
    PSMA RNA aptamer A10-3.2 conjugated with indocyanine green for rapid intraoperative imaging and effective mild photothermal therapy of prostate cancer.
    Yelisudan Mulati, Cong Lai, Jiawen Luo, Degeng Kong, Yunfei Xiao, Muhammad Usman, Cheng Liu, Kewei Xu.
      In prostate cancer (PCa) precision therapy, several challenges remain; among them, the delayed onset of intraoperative fluorescence imaging and the absence of targeted temperature control for local hyperthermia restrict the flexible perioperative use of tracers and increase the risk of thermal damage to adjacent sensitive tissues. To address these issues, we developed A10-3.2-ICG, a prostate-specific membrane antigen (PSMA)-targeting RNA aptamer conjugated with indocyanine green (ICG) via amine coupling. The probe was validated by mass spectrometry and spectroscopic analysis. For intraoperative imaging, A10-3.2-ICG demonstrated enhanced fluorescence and photothermal conversion efficiency compared to free ICG, enabling subminute delineation of PSMA-positive tumors with an imaging onset faster than most currently available intraoperative imaging probes for PCa, and sustained retention for 3-4 h in xenografts. Moreover, the probe effectively distinguished cancerous, adjacent, and benign tissues in clinical frozen sections. For therapy, A10-3.2-ICG enabled dose-tunable mild photothermal therapy (mPTT; 42-45 °C), which achieved 68.64 ± 5.34% tumor inhibition after repeated treatment cycles without inducing significant toxicity. This strategy overcomes the limitations of conventional PTT by offering precise thermal control with enhanced safety. Knockdown of AC026401.3, a novel therapeutic lncRNA target identified in our previous study-via siRNA transfection significantly inhibited PCa cell proliferation, migration, and invasion, and synergized with A10-3.2-ICG-mediated mPTT to enhance apoptosis. It also reduced SLC7A11 expression, suggesting a disruption of redox homeostasis in cancer cells. Taken together, this integrated strategy combining molecular targeting, real-time imaging, and localized mPTT, with optional gene regulation, offers a promising theranostic approach for precision management of PCa.
    Keywords:  Aptamer; Fluorescence-guided surgery; Mild photothermal therapy
    DOI:  https://doi.org/10.1016/j.ijbiomac.2026.150303
  41. Phytomedicine. 2026 Jan 07. pii: S0944-7113(26)00027-9. [Epub ahead of print] 157790
    Natural product-mediated autophagy targeting for prostate cancer: A novel potential therapeutic strategy.
    Maofu Zhang, Jialin Zhong, Maobin Yu, Junxin Wang, Tao Zhang, Meijun Liu, Peihai Zhang.
       BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies among middle-aged and elderly men. It exhibits persistently high global incidence and mortality rates. Given the limitations of conventional treatments, novel therapeutic approaches are urgently needed. Natural products offer distinct advantages, including low cost, reduced risk of drug resistance, and fewer side effects. Owing to their multi-component, multi-target, and multi-pathway regulatory properties, natural products have shown significant promise in PCa treatment.
    PURPOSE: This review investigates the regulatory effects of natural products on cellular autophagy and examines their roles in the initiation and progression of PCa. By proposing a novel natural product-autophagy-PCa axis, this study provides a framework for translating experimental findings into clinical practice and identifying potential therapeutic strategies for PCa.
    METHODS: A systematic review was conducted on cellular autophagy mechanisms and their association with PCa. Comprehensive searches were performed in authoritative databases, up to September 2025. Keywords included 'PCa', 'castration-resistant PCa', 'autophagy', 'autophagic flux', 'selective autophagy','macroautophagy','natural products', 'active compounds', 'traditional Chinese medicine (TCM) formulas', and 'TCM'. Additionally, this review explores single Chinese medicinal herbs, natural small-molecule compounds, and traditional Chinese medicinal formulae capable of regulating autophagy to improve PCa outcomes.
    RESULTS: Multiple natural products derived from plants, animals, and microorganisms effectively target cellular autophagy, thereby inducing apoptosis, inhibiting cell proliferation, migration, and invasion, delaying PCa progression, and demonstrating promising therapeutic effects. This review systematically outlines the origins, pharmacological actions, mechanisms, efficacy, and safety profiles of these natural products, highlighting their potential clinical benefits and providing a holistic perspective on their characteristics.
    CONCLUSIONS: This study fills existing gaps in the systematic characterisation of the relationship between autophagy and PCa, as well as in the development of natural product-based therapeutic strategies. It aims to offer more diverse treatment options to patients and contribute to advancements in PCa therapy.
    Keywords:  Autophagy; Mechanism studies; Natural products; Prostate cancer; Traditional Chinese medicine
    DOI:  https://doi.org/10.1016/j.phymed.2026.157790
  42. ACS Omega. 2026 Jan 13. 11(1): 810-825
    Folate-Functionalized Polymeric Nanoparticles for 5‑Fluorouracil Delivery to Prostate Cancer: Physicochemical and In Vitro/In Vivo Characterization.
    Bhumi Bhatt, Gajanan Kalyankar, Bhavin Vyas, Manisha Lalan, Nimeet Desai, Lalitkumar K Vora, Pranav Shah.
      Prostate cancer is the second most common cancer in men worldwide, highlighting the urgent need for effective and targeted chemotherapeutic approaches. This study reports the development and optimization of 5-fluorouracil (5-FU)-loaded poly-(lactic-co-glycolic acid)-polyethylene glycol-folic acid (PLGA-PEG-FOL) nanoparticles designed for folate receptor-mediated targeted therapy. The PLGA-PEG-FOL conjugate was synthesized via a stepwise carbodiimide coupling reaction and confirmed by FT-IR analysis. Nanoparticles were formulated via a modified emulsification-solvent evaporation method and optimized through a Box-Behnken design. The optimized formulation demonstrated a particle size of 178.47  ±  3.26 nm, a narrow polydispersity index (0.119  ±  0.008), a zeta potential of -23.4  ±  0.35 mV, a high entrapment efficiency (78.93  ±  1.05%), and sustained release of 5-FU for up to 72 h. In vitro cytotoxicity assays in PC-3 prostate cancer cells revealed a 1.6-fold reduction in the IC50 value compared with that of free 5-FU, indicating enhanced therapeutic potency. In vivo efficacy was evaluated in testosterone-induced prostate cancer in male Wistar rats. Compared with the control, treatment with 5-FU-loaded PLGA-PEG-FOL nanoparticles significantly reduced the prostate index and produced a 2.2-fold decrease in serum PSA levels and a 1.9-fold decrease in serum testosterone levels. Histopathological examination confirmed the attenuation of hyperplastic and dysplastic lesions in the nanoparticle-treated group. These findings suggest that PLGA-PEG-FOL nanoparticles are a promising targeted delivery platform for enhancing the therapeutic efficacy of 5-FU in prostate cancer treatment.
    DOI:  https://doi.org/10.1021/acsomega.5c07466
  43. Minerva Urol Nephrol. 2026 Jan 19.
    MRI prostate tumor volume predicts the need for systematic biopsies in patients undergoing MRI-targeted biopsy.
    Hanna Zurl, Stefan Embacher, Helmut Schöllnast, Emina Talakic, Stephanie Schöpfer-Schwab, Klara Pohl, Lukas Scheipner, Samra Jasarevic, Julia Altziebler, Anna Mangge, Sebastian Mannweiler, Jakob Riedl, Uros Bele, Conrad Leitsmann, Marianne Leitsmann, Georg Hutterer, Sascha Ahyai, Johannes Mischinger.
       BACKGROUND: Combined transrectal mpMRI-TRUS targeted (TB) and systematic biopsy (SB) is widely used to diagnose prostate cancer (PCa). However, SB may be omitted in a subset of patients with minimal risk of missing clinically significant prostate cancer (csPCa) in TB alone. We aimed to identify clinical characteristics predicting the need for SB in men undergoing TB.
    METHODS: In this retrospective cohort study, 879 patients underwent combined TB and SB. Cases where csPCa was missed by TB but detected by SB were identified. Logistic regression analysis was used to identify clinical predictors for SB necessity, including digital rectal examination, prior negative biopsy, age, prostate-specific antigen (PSA), prostate volume, PSA density, mpMRI tumor volume (MTV), number of mpMRI lesions, PI-RADS score, and mpMRI tesla.
    RESULTS: In 80 (9.1%) cases csPCa was missed by TB and detected by SB only. Median MTV was 0.75 cm3 (IQR 0.43-1.41 cm3). Multivariable logistic regression analysis revealed MTV as the only significant predictor of csPCa missed by TB alone (OR=0.52, 95% CI 0.36, 0.75, P<0.001). A larger MTV was inversely associated with the risk of missing csPCa in TB alone. In patients with an MTV greater than 1.36 cm3, the rate of missing csPCa with TB alone was ≤5%.
    CONCLUSIONS: MTV is a promising predictor to identify patients who may not require a concomitant SB when undergoing TB. However, this finding needs to be validated in external cohorts before being applied in clinical practice.
    DOI:  https://doi.org/10.23736/S2724-6051.25.06375-X
  44. Aktuelle Urol. 2026 Jan 22.
    [Therapy-Associated Neuroendocrine Prostate Cancer (tNEPC): A Diagnostic and Therapeutic Challenge in Uro-Oncology with Emerging Clinical Implications].
    Gunhild von Amsberg, Arndt Hartmann, Markus Eckstein, Isabel Heidegger.
      Therapy-associated neuroendocrine prostate cancer (tNEPC) is a rare, prognostically unfavourable variant of castration-resistant prostate cancer that typically arises under conditions of androgen deprivation or androgen receptor signalling inhibition. The underlying process of transdifferentiation is promoted by genetic alterations - most notably the loss of TP53, RB1, and PTEN - as well as epigenetic reprogramming and influences from the tumour microenvironment. Clinically, tNEPC is characterised by aggressive behaviour, the development of visceral and osteolytic metastases, lack of correlation between PSA levels and tumour burden, and PSMA-negative imaging findings. The updated German S3 guideline recommends histological re-biopsy in appropriate clinical scenarios.Histologically, tNEPC is categorised into three subtypes: small-cell neuroendocrine carcinoma (SCNEC), large-cell neuroendocrine carcinoma (LCNEC), and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) with both neuroendocrine and adenocarcinomatous components. In its fifth edition, the WHO formally recognised tNEPC as a distinct pathological entity. Immunohistochemical diagnosis relies on the detection of markers such as synaptophysin, chromogranin A, CD56, and INSM1.In addition to histology, [¹⁸F]-FDG and DOTA-based PET/CT imaging modalities, as well as emerging liquid biopsy approaches (e.g., circulating tumour cells, cfDNA methylation), are increasingly relevant for diagnostic and disease-monitoring purposes. At present, platinum-based chemotherapy remains the standard treatment. Novel therapeutic approaches target molecular structures such as AURKA, EZH2, and DLL3. In selected cases, peptide receptor radionuclide therapy (PRRT) may be considered in patients with positive somatostatin receptor expression. Due to biological heterogeneity and limited evidence, tNEPC requires individualised, interdisciplinary management. This review summarises current insights into the pathogenesis, diagnosis, and therapeutic strategies of tNEPC and provides an outlook on future developments.
    DOI:  https://doi.org/10.1055/a-2768-8830
  45. N Engl J Med. 2026 Jan 22. pii: 10.1056/NEJMc2517122#sa2. [Epub ahead of print]394(4): 410
    European Study of Prostate Cancer Screening - 23-Year Follow-up.
    Ian M Thompson.
      
    DOI:  https://doi.org/10.1056/NEJMc2517122
  46. Clin Cancer Res. 2026 Jan 22.
    Synergistic treatment of prostate cancer and multiple myeloma using CD46-targeted radioimmunotherapy-antibody drug conjugates.
    Anil P Bidkar, Scott Bidlingmaier, Anju Wadhwa, Ellis Mayne, Athira Raveendran, Shubhankar Naik, Cheng Xue, Megha Basak, Kondapa Naidu Bobba, Bonell Patiño-Escobar, Nancy Greenland, Juan Antonio Camara Serrano, Veronica Steri, Jonathan Chou, Arun Wiita, Jiang He, David M Wilson, Rahul Aggarwal, Henry F VanBrocklin, Youngho Seo, Bin Liu, Robert R Flavell.
       PURPOSE: CD46 is highly expressed across multiple cancer types, including prostate cancer and multiple myeloma. We have developed CD46-targeting antibody drug conjugate and 225Ac-based alpha particle therapy agents that demonstrated a tumor-selective therapeutic effect. We hypothesized that a treatment strategy targeting CD46 using simultaneous antibody-drug conjugate (ADC) and radioimmunotherapy (RIT) methods would have synergistic therapeutic efficacy with acceptable toxicity.
    EXPERIMENTAL DESIGN: Two CD46-targeted combination treatment strategies were evaluated: (1) co-administration of the ADC (YS5-MMAE) and Actinium-225-labeled antibody ([225Ac]Macropa-PEG4-YS5), and (2) a dual-payload radioconjugate ([225Ac]Macropa-PEG4-YS5-MMAE, R-ADC). The in vitro synergy was studied using cell viability, DNA damage, and apoptosis assays. In vivo studies were performed for biodistribution, toxicity, and therapeutic evaluation in subcutaneous, disseminated, and patient-derived xenograft models of prostate cancer and multiple myeloma.
    RESULTS: Combination therapy induced synergistic G2/M arrest, increased γ-H2AX foci, and enhanced cell death compared to monotherapies. R-ADC and co-administration strategies resulted in improved tumor control and survival benefit.
    CONCLUSIONS: By integrating orthogonal microtubule inhibition and high-linear-energy-transfer alpha irradiation on a single CD46 scaffold, potent, well-tolerated tumor control was achieved across diverse models. The dual-payload construct's compatibility with CD46 immuno-PET for real-time dosimetry further supports progression to early-phase clinical trials in prostate cancer and multiple myeloma.
    DOI:  https://doi.org/10.1158/1078-0432.CCR-25-4110
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