bims-meproc Biomed News
on Metabolism in Prostate Cancer
Issue of 2025–08–03
fourteen papers selected by
Grigor Varuzhanyan, UCLA
  1. Study of the interaction between cardiometabolic index and inflammatory index on the risk of prostate cancer development.
  2. Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer.
  3. PCP4 inhibits the progression of prostate cancer through Ca2+/CAMKK2/AMPK/AR pathway.
  4. Dual role of hydrogen sulfide in the tumor microenvironment of prostate cancer (Review).
  5. Rewiring cancer metabolism: oncogenic signaling pathways and targeted therapeutics.
  6. Exploring the prognostic significance and therapeutic potential of SUCLG2 in prostate cancer.
  7. Evaluation of newly synthesized schiff base Pd(II) complexes for prostate cancer treatment through in vitro cytotoxicity and molecular mechanistic studies.
  8. Effect of TP53 mutation, expression and polymorphism on the survival, immune infiltration and ferroptosis in patients with prostate cancer.
  9. Imaging the uptake and metabolism of glutamine in prostate tumor models using CEST MRI.
  10. Data-Independent Acquisition (DIA)-Based Label-Free Redox Proteomics (DIALRP) Identifies Prominent Cysteine Oxidations in Translation Machinery in Prostate Cancer Cells Under Oxidative Stress.
  11. Impact of Metastatic Microenvironment on Physiology and Metabolism of Small Cell Neuroendocrine Prostate Cancer Patient-Derived Xenografts.
  12. The 31st Annual Prostate Cancer Foundation Scientific Retreat Report.
  13. Integrating 68Ga-PSMA-11 PET/CT with Clinical Risk Factors for Enhanced Prostate Cancer Progression Prediction.
  14. A Subset of HOX Genes Negatively Correlates with HOX/PBX Inhibitor Target Gene Expression and Is Associated with Apoptosis, DNA Repair, and Metabolism in Prostate Cancer.
  1. Front Immunol. 2025 ;16 1591879
    Study of the interaction between cardiometabolic index and inflammatory index on the risk of prostate cancer development.
    Yunyun Xiao, Bei Tang, Jueqi Wang, Zhiruo Cai, Hengqing An, Ning Tao.
       Background: Prostate cancer (PCa) is an important cause of fatality in older men, with inflammation and metabolic disorders as risk factors for PCa. This study examined how systemic inflammation, measured by inflammatory indices, interacts with the cardiometabolic index (CMI), a marker of obesity and dyslipidemia, to influence the risk of developing PCa.
    Methods: This study consisted of 1,591 male patients recruited from the Department of Urology at the First Affiliated Hospital of Xinjiang Medical University between 2022 and 2024. Propensity score matching was employed to adjust the sample size, resulting in a final cohort of 149 PCa patients and 296 matched controls. Logistic regression models and restricted cubic spline (RCS) analyses were employed to evaluate the associations between CMI and various inflammatory indices (e.g., PIV, SIRI, PLR, NLR, LMR) with prostate cancer. Interaction tests were conducted to investigate the impact of the interplay between inflammatory indices and CMI on the risk of prostate cancer.
    Results: NLR, PLR, PIV, and SIRI were significantly positively associated with prostate cancer (PCa) risk, whereas LMR exhibited a significant negative association. The CMI was significantly associated with an elevated risk of prostate cancer (PCa) (OR = 1.97, 95% CI: 1.38~2.81). Restricted cubic spline (RCS) analysis revealed a nonlinear dose-response relationship between CMI and prostate cancer (PCa) risk, with the risk plateauing at CMI ≈ 0.65. Sensitivity analyses confirmed the robustness of these results. Significant interactions were observed between CMI and inflammatory indices, particularly NLR, PLR, and LMR, suggesting synergistic effects on prostate cancer (PCa) risk.
    Conclusions: The present study demonstrated that inflammation indicators and CMI exhibited a strong association with the risk of PCa. Furthermore, a significant interaction was observed between CMI and inflammation indicators. These findings provide a novel perspective for PCa risk prediction and prevention, suggesting that inflammation and metabolic status should be considered together when assessing PCa risk.
    Keywords:  cardiometabolic index; inflammation; lymphocyte monocyte ratio; neutrophillymphocyte ratio; platelet lymphocyte ratio; prostate cancer; systemic inflammation response index
    DOI:  https://doi.org/10.3389/fimmu.2025.1591879
  2. Biomedicines. 2025 Jul 04. pii: 1642. [Epub ahead of print]13(7):
    Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer.
    Mohammad Esfini Farahani, Yanquan Zhang, Amos Olalekan Akinyemi, Fatemeh Seilani, Md Rakibul Alam, Xiaoqi Liu.
      Prostate cancer (PCa) is a highly heterogeneous disease, with castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) representing its most aggressive and therapy-resistant forms. Emerging evidence indicates that lineage plasticity-driven by key transcription factors such as Octamer Binding Factor 4 (OCT4)-plays a crucial role in therapeutic resistance and disease progression. OCT4, in coordination with SOX2 and NANOG, acts as a master regulator of stemness and is frequently upregulated in prostate cancer stem cells (PCSCs). This upregulation contributes to tumor initiation, metastasis, and resistance to both androgen deprivation therapy (ADT) and chemotherapy. In this review, we explore the role of OCT4 in mediating lineage plasticity in prostate cancer, with particular emphasis on its involvement in treatment resistance and neuroendocrine differentiation. We also examine therapeutic strategies aimed at targeting OCT4 directly, such as microRNA-mediated suppression, small-molecule inhibitors, and suicide gene therapy, as well as indirect approaches that modulate OCT4 expression via FGFR and NF-κB signaling pathways. While these strategies offer promising avenues, challenges such as adaptive resistance and the intricate signaling networks within PCSCs remain significant hurdles. A deeper understanding of the molecular mechanisms underlying OCT4-driven plasticity may pave the way for novel therapeutic approaches and improved outcomes in advanced prostate cancer.
    Keywords:  androgen deprivation therapy; castration-resistant prostate cancer; neuroendocrine prostate cancer; octamer-binding transcription factor 4; prostate cancer stem cells
    DOI:  https://doi.org/10.3390/biomedicines13071642
  3. Front Immunol. 2025 ;16 1616046
    PCP4 inhibits the progression of prostate cancer through Ca2+/CAMKK2/AMPK/AR pathway.
    Wenqiao Jia, Zeyuan Yu, Feifei Sun, Ping Liu, Bo Han.
       Background: The development of prostate cancer (PCa) remains a major health threat for men worldwide. Calcium/Calmodulin signaling pathway has been implicated to the initiation and progression of diverse human cancers. Loss or downregulation of Purkinje cell protein 4 (PCP4), is frequently observed in some prostate cancer patients, particularly those with castration-resistant prostate cancer (CRPC).
    Methods: Public datasets were used to analyze PCP4 expression and the relationship between PCP4 expression and clinicopathological characteristics of PCa patients. Gain- and loss-of-function studies in PCa cell lines and mouse models were performed to characterize the role of PCP4 in tumor progression. A series of molecular and biochemical experiments were carried out in PCa cell lines to investigate the mechanism underlying PCP4-mediated tumor suppression.
    Results: (1) PCP4 gene loss occurs at high frequency in PCa patients, and decreased expression of PCP4 correlates with poor prognosis of PCa, particularly CRPC development; (2) TMPRSS2-ERG fusion frequently co-occurs with PCP4 deletion; (3) PCP4 suppresses prostate cancer progression in vitro and in vivo; (4) PCP4 is an androgen receptor (AR) suppressed gene; (5) PCP4 was involved in the stabilization of CAMKK2 protein; (6) PCP4 inhibits PCa progression by regulating Ca2+/CAMKK2/AMPK/AR signaling axis.
    Conclusion: Our findings elucidate the molecular mechanism that PCP4 downregulation promotes PCa progression via Ca2+/CAMKK2/AMPK/AR pathway, highlighting its significance in CRPC development.
    Keywords:  CRPC; PCP4; PEP-19; progression; prostate cancer
    DOI:  https://doi.org/10.3389/fimmu.2025.1616046
  4. Mol Med Rep. 2025 Oct;pii: 272. [Epub ahead of print]32(4):
    Dual role of hydrogen sulfide in the tumor microenvironment of prostate cancer (Review).
    Hua Luo.
      Tumor microenvironment (TME) dynamics and the critical dual role of hydrogen sulfide (H2S) in prostate cancer (PCa) biology are discussed in the present review. PCa remains one of the most prevalent malignancies in men, with advanced castration‑resistant PCa presenting substantial therapeutic challenges. H2S, an endogenous gaseous signaling molecule, is a key regulator of biological processes, including immune modulation, cell proliferation and apoptosis, during tumor progression. H2S exhibits paradoxical effects in PCa by promoting tumorigenesis and exerting context‑dependent antitumor activity. H2S mediates these outcomes through key signaling pathways, including the PI3K/AKT and MAPK/ERK pathways, which regulate tumor cell survival and metastasis. The present review emphasizes how H2S regulates tumor cell dynamics and immune interactions in a concentration‑dependent manner within the TME, making it a promising therapeutic target to overcome resistance to conventional treatments. Future research should prioritize translating these findings into clinical strategies, particularly through the development of H2S‑modulating therapies tailored to the TME, offering potential for overcoming resistance in advanced PCa.
    Keywords:  hydrogen sulfide; prostate cancer; signaling pathways; tumor microenvironment
    DOI:  https://doi.org/10.3892/mmr.2025.13637
  5. Sci China Life Sci. 2025 Jul 25.
    Rewiring cancer metabolism: oncogenic signaling pathways and targeted therapeutics.
    Siying Lyu, Nina Gildor, Qing Zhang, Chengheng Liao.
      Metabolic reprogramming is a hallmark of cancer, playing a critical role in tumorigenesis by supporting cancer cell survival, proliferation, metastasis, and immune evasion. Oncogenic signaling pathways regulate key metabolic processes by orchestrating gene expression and enhancing metabolic enzyme activity, ensuring cancer cells meet their bioenergetic and biosynthetic demands. Here, we highlight the roles of major oncogenic metabolic signaling pathways, including phosphoinositide 3-kinase (PI3K)/AKT, Myc, p53, and hypoxia-inducible factor (HIF), in driving metabolic rewiring. We provide a conceptual framework to understand why metabolic reprogramming occurs in tumor cells, how metabolic alterations contribute to tumorigenesis, metastasis, and immune evasion, and the therapeutic implications of targeting these metabolic vulnerabilities in cancer.
    Keywords:  cancer metabolism; cell proliferation; immune evasion; metastasis; oncogenic signaling pathways; target therapy
    DOI:  https://doi.org/10.1007/s11427-025-2979-3
  6. Front Genet. 2025 ;16 1592779
    Exploring the prognostic significance and therapeutic potential of SUCLG2 in prostate cancer.
    Bao Hua, Qing Yang, Shangqing Song, Wenfeng Li, Bin Xu, Yufei Gu.
       Background: Prostate cancer (PCa), a highly heterogeneous cancer with a complex molecular pathogenesis, is a leading cause of cancer-related mortality among men globally. The present study presents a lipid metabolism-based risk model for PCa and explores the role of succinyl-CoA ligase GDP-forming subunit beta (SUCLG2), a potential marker and therapeutic target in PCa involved in lipid metabolism and cancer progression, from the perspective of developing effective diagnostic and therapeutic strategies.
    Methods: High-throughput RNA sequencing and single-cell RNA sequencing were used to investigate the expression and functional relevance of SUCLG2 in PCa. We analyzed 497 PCa samples from The Cancer Genome Atlas and conducted a comprehensive bioinformatics analysis, including univariate Cox proportional hazards regression, least absolute shrinkage and selection operator regression, and gene set enrichment analysis. Furthermore, quantitative real-time polymerase chain reaction and immunofluorescence assays were performed to validate SUCLG2 expression in clinical samples and the prostate carcinoma epithelial cell line 22Rv1.
    Results: Our findings revealed that lipid metabolism-related genes, including SUCLG2, have significant prognostic value, based on a 16-gene risk model constructed that accurately predicted PCa prognosis. In particular, SUCLG2 was significantly enriched in luminal and basal/intermediate cell subsets, highlighting its potential role in tumor progression and therapy resistance. Drug sensitivity analysis indicated that SUCLG2 expression is correlated with the efficacy of several chemotherapeutic agents, based on which strategies for personalized therapy in PCa treatment could be devised.
    Conclusion: SUCLG2 plays a pivotal role in the metabolic reprogramming of PCa, thus offering new insights into its progression and potential therapeutic targets. Our study underscores the importance of metabolic pathways in PCa pathogenesis and paves the way for the development of targeted therapies, thus contributing to personalized medicine in PCa management.
    Keywords:  SUCLG2; lipid metabolism; personalized therapy; prostate cancer; single-cell RNA sequencing
    DOI:  https://doi.org/10.3389/fgene.2025.1592779
  7. Front Chem. 2025 ;13 1636477
    Evaluation of newly synthesized schiff base Pd(II) complexes for prostate cancer treatment through in vitro cytotoxicity and molecular mechanistic studies.
    Damnjan Pantic, Nikola Mirkovic, Tatjana Vulovic, Danijela Jovanovic, Stefan Jakovljevic, Petar Canovic, Milan Zaric, Radica Zivkovic Zaric, Marina Kostic, Jovana Dragojevic, Vera Divac, Ziko Milanovic, Kristina Milisavljevic, Marina Mitrovic, Ivanka Zelen.
       Introduction: Palladium (II) complexes are promising anticancer agents with potential advantages over platinum drugs. This study aimed to synthesize and characterize three new Pd(II) complexes (2a-2c) with Schiff base ligands derived from salicylic acid and amine scaffolds, and to evaluate their antitumor activity against prostate cancer cells.
    Methods: The Pd(II) complexes were synthesized and structurally characterized. Cytotoxicity was tested on two human prostate cancer cell lines (PC-3, DU-145) and healthy fibroblasts (MRC-5). Apoptosis induction was assessed by flow cytometry, with a focus on Bcl-2 and caspase proteins. Molecular docking was used to examine binding to the androgen receptor (AR) and apoptotic regulators (CASP3, BCL2, BAX). DNA and human serum albumin (HSA) binding were also investigated.
    Results: All complexes showed significant cytotoxicity. Notably, complex 2c exhibited more potent cytotoxic activity than cisplatin in prostate cancer cell lines, with lower IC50 values after 72 h exposure in DU-145 (7.1 µM vs. 8.2 µM) and PC-3 cells (8.6 µM vs. 21.9 µM), while showing reduced toxicity in normal MRC-5 cells (42.3 µM vs. 24.4 µM). Apoptosis was confirmed as the primary cytotoxic mechanism, involving the activation of Bcl-2 and caspases. Docking studies revealed that complex 2c had the strongest binding affinity to AR and apoptotic proteins, mediated by hydrogen bonds, π-π stacking, and hydrophobic interactions. DNA and HSA binding supported their biological relevance.
    Conclusion: Complex 2c exhibits potent anticancer activity through the induction of apoptosis and dual targeting of the AR and apoptotic pathways, making it a promising candidate for further development of anticancer drugs.
    Keywords:  DNA; albumin; apoptosis; cytotoxicity; palladium; prostate cancer; schiff bases
    DOI:  https://doi.org/10.3389/fchem.2025.1636477
  8. Oncol Lett. 2025 Sep;30(3): 445
    Effect of TP53 mutation, expression and polymorphism on the survival, immune infiltration and ferroptosis in patients with prostate cancer.
    Gui-Min Wen, Zhen-Ying Zhao, Xiao-Hui Zheng, Da-Hua Liu, Pu Xia.
      Tumor protein 53 (TP53) serves a key role in the prevention of tumor formation, while TP53 mutation can lead to uncontrolled cell division and tumorigenesis. Men carrying TP53 mutations have a higher risk of developing invasive prostate cancer. Notably, there are distinct epidemiological and genomic features between Chinese and Western patients with prostate cancer, wherein TP53 mutations are more prevalent among Chinese patients. However, the effect of TP53 mutations, expression and polymorphisms on prostate cancer remain to be elucidated. Therefore, in the present study, bioinformatics analyses and meta-analysis were conducted to assess how TP53 mutations and expression affect the prognosis and tumor microenvironment in patients with prostate cancer. Additionally, the role of TP53 in ferroptosis was also investigated in vitro. The results indicated that high TP53 expression was a prognostic factor associated with poor outcomes in patients with prostate cancer. In addition, bioinformatics analysis using The Cancer Genome Atlas database demonstrated significant differences in immune cell infiltration and in the expression of ferroptosis-related genes between wild-type and mutant TP53 prostate cancer tissues, as well as between high and low TP53-expressing tumors. Furthermore, erastin, a well-known inducer of ferroptosis, triggered ferroptosis in prostate cancer cells via downregulation of solute carrier family 7 member 11 and glutathione peroxidase 4, independent of TP53 expression. However, reactive oxygen species levels were markedly higher in TP53-expressing cells, LnCAP and DU145, compared with TP53-null cells, PC3 cells. Overall, the results of the present study could provide a potential novel therapeutic target for the treatment of prostate cancer in the future.
    Keywords:  ferroptosis; mutation; polymorphism; prostate cancer; tumor protein 53
    DOI:  https://doi.org/10.3892/ol.2025.15191
  9. Npj Imaging. 2025 Aug 01. 3(1): 34
    Imaging the uptake and metabolism of glutamine in prostate tumor models using CEST MRI.
    Yuki Hodo, Caitlin M Tressler, Behnaz Ghaemi, Rebecca Thomas, Aliyah S Webster, Kirsten N Bains Williams, Yuguo Li, Martin G Pomper, Chi V Dang, Zaver M Bhujwalla, Jeff W M Bulte, Peter C M van Zijl, Aline M Thomas.
      Glutamine metabolism is upregulated in many cancers. While multiple glutamine imaging agents have been developed and translated to clinical use, the short half-lives of their signal and instability in vivo limit the aspects of glutamine metabolism they capture. In phantoms at physiological pH, chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) contrast was observed at 11.7 T from glutamine, downstream metabolic products (glutamate and ammonia) and their co-substrates (alanine, aspartate, and cystine/cysteine). This contrast increased at lower pH. These results suggest that both uptake and metabolism of glutamine would increase CEST signal enhancement. We then investigated the feasibility of imaging the uptake (delivery, transport and metabolism) of naturally-occuring glutamine using CEST MRI in preclinical prostate cancer models, wherein key metabolic proteins are the glutamine transporter ASCT2 and as well as enzymes GLS1, ALT2 (GPT2), AST1 (GOT1), and GDH1 (GLUD1). The LNCaP prostate cancer line exhibited higher expression of ASCT2, GDH1, ALT2, and AST1 compared to DU-145 cells. CEST MRI enhancement upon administration of glutamine was consistently higher in LNCaP 3D spheres (phantoms) and tumors (in vivo) than their DU-145 counterparts. Mass spectrometry imaging confirmed higher uptake and metabolism of glutamine in LNCaP tumors. These findings demonstrate that CEST MRI of glutamine is capable of distinguishing preclinical prostate tumor models that differ in glutamine uptake and has potential for translation to clinical use.
    DOI:  https://doi.org/10.1038/s44303-025-00100-3
  10. J Proteome Res. 2025 Jul 31.
    Data-Independent Acquisition (DIA)-Based Label-Free Redox Proteomics (DIALRP) Identifies Prominent Cysteine Oxidations in Translation Machinery in Prostate Cancer Cells Under Oxidative Stress.
    Daiki Kobayashi, Tomoyo Takami, Masaki Matsumoto.
      Oxidative stress is a key factor in numerous physiological and pathological processes, including aging, cancer, and neurodegenerative diseases. Protein cysteine residues are particularly susceptible to oxidative stress-induced modifications that can alter their structure and function, thereby affecting intracellular signaling pathways. In this study, we performed a data-independent acquisition mass spectrometry (DIA-MS)-based label-free redox proteomics method, termed DIALRP, to comprehensively analyze cysteine oxidative modifications in the prostate cancer cell line DU145 under oxidative stress induced by menadione (MND). Of 10,821 cysteine-containing peptides identified, we successfully quantified the redox changes in 3665 peptides. We also observed that 1407 peptides were significantly oxidized in response to MND treatment. Gene ontology analysis revealed that a group of translation-related molecules was most enriched among highly MND-sensitive cysteine-containing proteins. Notably, our data demonstrated that MND-induced oxidative stress inhibits EIF2, EIF6, and EEF2 complex formation, suggesting that these complex inhibitions become functional factors for a dramatic reduction in translation activity. Our results show that DIALRP is utilized as a robust and cost-effective approach for investigating redox-regulated cellular processes. Moreover, these findings provide significant insights into translation regulation under oxidative stress and provide a valuable framework for future studies on redox-mediated cellular processes.
    Keywords:  cancer; data-independent acquisition; oxidative stress; redox proteomics; translation factors
    DOI:  https://doi.org/10.1021/acs.jproteome.5c00339
  11. Cancers (Basel). 2025 Jul 18. pii: 2385. [Epub ahead of print]17(14):
    Impact of Metastatic Microenvironment on Physiology and Metabolism of Small Cell Neuroendocrine Prostate Cancer Patient-Derived Xenografts.
    Shubhangi Agarwal, Deepti Upadhyay, Jinny Sun, Emilie Decavel-Bueff, Robert A Bok, Romelyn Delos Santos, Said Al Muzhahimi, Rosalie Nolley, Jason Crane, John Kurhanewicz, Donna M Peehl, Renuka Sriram.
      Background: Potent androgen receptor pathway inhibitors induce small cell neuroendocrine prostate cancer (SCNC), a highly aggressive subtype of metastatic androgen deprivation-resistant prostate cancer (ARPC) with limited treatment options and poor survival rates. Patients with metastases in the liver have a poor prognosis relative to those with bone metastases alone. The mechanisms that underlie the different behavior of ARPC in bone vs. liver may involve factors intrinsic to the tumor cell, tumor microenvironment, and/or systemic factors, and identifying these factors is critical to improved diagnosis and treatment of SCNC. Metabolic reprogramming is a fundamental strategy of tumor cells to colonize and proliferate in microenvironments distinct from the primary site. Understanding the metabolic plasticity of cancer cells may reveal novel approaches to imaging and treating metastases more effectively. Methods: Using magnetic resonance (MR) imaging and spectroscopy, we interrogated the physiological and metabolic characteristics of SCNC patient-derived xenografts (PDXs) propagated in the bone and liver, and used correlative biochemical, immunohistochemical, and transcriptomic measures to understand the biological underpinnings of the observed imaging metrics. Results: We found that the influence of the microenvironment on physiologic measures using MRI was variable among PDXs. However, the MR measure of glycolytic capacity in the liver using hyperpolarized 13C pyruvic acid recapitulated the enzyme activity (lactate dehydrogenase), cofactor (nicotinamide adenine dinucleotide), and stable isotope measures of fractional enrichment of lactate. While in the bone, the congruence of the glycolytic components was lost and potentially weighted by the interaction of cancer cells with osteoclasts/osteoblasts. Conclusion: While there was little impact of microenvironmental factors on metabolism, the physiological measures (cellularity and perfusion) are highly variable and necessitate the use of combined hyperpolarized 13C MRI and multiparametric (anatomic, diffusion-, and perfusion- weighted) 1H MRI to better characterize pre-treatment tumor characteristics, which will be crucial to evaluate treatment response.
    Keywords:  glycolysis; hyperpolarized carbon-13 magnetic resonance imaging; metabolism; metastases; microenvironment; perfusion; physiology; small cell neuroendocrine cancer
    DOI:  https://doi.org/10.3390/cancers17142385
  12. Prostate. 2025 Jul 27.
    The 31st Annual Prostate Cancer Foundation Scientific Retreat Report.
    Andrea K Miyahira, Howard R Soule.
       BACKGROUND: The 31st Annual Prostate Cancer Foundation (PCF) Scientific Retreat took place in Carlsbad, CA on October 24-26, 2024.
    METHODS: The Annual PCF Scientific Retreat is the foremost international conference focused on emerging and cutting-edge basic, translational, and clinical prostate cancer research, as well as research from related disciplines with strong potential to advance prostate cancer understanding and improve patient outcomes.
    RESULTS: The 2024 PCF Retreat featured research from many disciplines, including: (i) tumor metabolism; (ii) genomics of prostate cancer racial disparities; (iii) reprogramming macrophages in the tumor immune microenvironment; (iv) high impact clinical trials for patients with prostate cancer; (v) artificial intelligence (AI) in driving innovation in cancer research and cancer care; (vi) lessons from 20 years of STAMPEDE; (vii) the PCF-Veterans Administration (VA) partnership's impact in bringing precision medicine to Veterans; (viii) germline DNA damage repair variants and prognosis of patients with high-risk or metastatic prostate cancer; (ix) next generation theranostics; (x) emerging immunotherapies; (xi) advanced molecular biology of lethal prostate cancer; (xii) posttranscriptional gene regulation in prostate cancer; (xiii) new biotechnologies in genomic medicine; (xiv) advances in "in vivo" cell therapy platforms and novel small molecule cancer therapies; and (xv) an announcement on the PCF Gender Equity Networking Initiative.
    CONCLUSIONS: This report highlights key presentations from the 2024 PCF Scientific Retreat, with the aim of enhancing understanding of ongoing and emerging research, driving future progress in prostate cancer science and patient care, and inspiring broader public support for cancer research.
    Keywords:  androgen receptor; diagnosis; prognosis; therapy; tumor biology
    DOI:  https://doi.org/10.1002/pros.70015
  13. Cancers (Basel). 2025 Jul 09. pii: 2285. [Epub ahead of print]17(14):
    Integrating 68Ga-PSMA-11 PET/CT with Clinical Risk Factors for Enhanced Prostate Cancer Progression Prediction.
    Joanna M Wybranska, Lorenz Pieper, Christian Wybranski, Philipp Genseke, Jan Wuestemann, Julian Varghese, Michael C Kreissl, Jakub Mitura.
       BACKGROUND/OBJECTIVES: This study evaluates whether combining 68Ga-PSMA-11-PET/CT derived imaging biomarkers with clinical risk factors improves the prediction of early biochemical recurrence (eBCR) or clinical progress in patients with high-risk prostate cancer (PCa) after primary treatment, using machine learning (ML) models.
    METHODS: We analyzed data from 93 high-risk PCa patients who underwent 68Ga-PSMA-11 PET/CT and received primary treatment at a single center. Two predictive models were developed: a logistic regression (LR) model and an ML derived probabilistic graphical model (PGM) based on a naïve Bayes framework. Both models were compared against each other and against the CAPRA risk score. The models' input variables were selected based on statistical analysis and domain expertise including a literature review and expert input. A decision tree was derived from the PGM to translate its probabilistic reasoning into a transparent classifier.
    RESULTS: The five key input variables were as follows: binarized CAPRA score, maximal intraprostatic PSMA uptake intensity (SUVmax), presence of bone metastases, nodal involvement at common iliac bifurcation, and seminal vesicle infiltration. The PGM achieved superior predictive performance with a balanced accuracy of 0.73, sensitivity of 0.60, and specificity of 0.86, substantially outperforming both the LR (balanced accuracy: 0.50, sensitivity: 0.00, specificity: 1.00) and CAPRA (balanced accuracy: 0.59, sensitivity: 0.20, specificity: 0.99). The decision tree provided an explainable classifier with CAPRA as a primary branch node, followed by SUVmax and specific PET-detected tumor sites.
    CONCLUSIONS: Integrating 68Ga-PSMA-11 imaging biomarkers with clinical parameters, such as CAPRA, significantly improves models to predict progression in patients with high-risk PCa undergoing primary treatment. The PGM offers superior balanced accuracy and enables risk stratification that may guide personalized treatment decisions.
    Keywords:  68Ga-PSMA-11 PET/CT; CAPRA score; SUVmax; early biochemical recurrence; outcome prediction; prostate cancer
    DOI:  https://doi.org/10.3390/cancers17142285
  14. Genes (Basel). 2025 Jul 15. pii: 824. [Epub ahead of print]16(7):
    A Subset of HOX Genes Negatively Correlates with HOX/PBX Inhibitor Target Gene Expression and Is Associated with Apoptosis, DNA Repair, and Metabolism in Prostate Cancer.
    Richard Morgan, Christopher Smith, Hardev Pandha.
       BACKGROUND/OBJECTIVES: The HOX genes encode a family of homeodomain-containing transcription factors that have important roles in defining cell and tissue identity in embryonic development, but which also show deregulated expression in many cancers and have been shown to have pro-oncogenic roles. Due to their functionally redundant nature, strategies to target HOX protein function in cancer have focused on their interaction with their PBX cofactor using competitive peptides such as HXR9. HOX/PBX inhibition triggers apoptosis through a sudden increase in target gene expression, including Fos, DUSP1, and ATF3, which are otherwise repressed by HOX/PBX binding.
    METHODS: We analyzed publicly available transcriptomic data in the R2 platform.
    RESULTS: We show that a specific subgroup of HOX genes is negatively correlated with Fos, DUSP1, and ATF3 expression in prostate cancer, and that this subgroup also shows a strong positive corelation with pathways that support tumour growth, most notably DNA repair and aminoacyl tRNA biosynthesis, and a negative correlation with genes that promote cell adhesion and prevent motility. In addition, this set of HOX genes strongly correlates with patient age, reflecting a previously identified progressive loss of regulation of HOX expression in normal peripheral blood cells.
    CONCLUSIONS: Our findings indicate these HOX genes may have pro-oncogenic functions in prostate cancer.
    Keywords:  ATF3; DUSP1; HOX; HXR9; PBX; ageing
    DOI:  https://doi.org/10.3390/genes16070824
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