Prostate cancer (PCa) is one of the most common malignancies in men worldwide, and its current diagnostic and therapeutic methods still face severe challenges in terms of specificity, efficacy, and toxicity. The emergence of nanotechnology provides a powerful platform to overcome these obstacles. Through the design of sophisticated nanocarriers, targeted delivery and controlled release of therapeutic agents, as well as the synergy of multiple treatment modalities, can be achieved, thereby significantly improving efficacy and reducing side effects. Meanwhile, nanotechnology shows great potential in developing highly sensitive diagnostic tools and theranostic platforms, laying the foundation for early detection and precise treatment of PCa. Although challenges such as scalability and safety remain to be addressed before clinical translation, nanotechnology is undoubtedly reshaping the landscape of PCa management and driving the field towards personalized medicine. This review aims to provide a systematic overview of significant advancements in nanotechnology for the diagnosis and treatment of PCa over the past three years. It focuses on innovative research in novel nanocarrier design, targeting strategies, and the construction of integrated diagnostic and therapeutic platforms. Furthermore, current challenges and future directions for clinical translation are discussed, with the aim of offering valuable insights and references for researchers and clinicians in this field.

Prostate cancer (PCa) is a major global cancer burden in men, and its treatment is hindered by the immunosuppressive tumor microenvironment. In this context, PCa initially shows a favorable response to immunotherapy. However, as the disease progresses, the tumor gradually develops resistance to immunotherapy, with tumor-associated macrophages (TAMs) being key drivers. TAMs promote inflammation, angiogenesis, stromal remodeling, and immune evasion, leading to the development of castration-resistant PCa. The traditional M1/M2 dichotomy, such as proliferative-TAM (Prolif-TAM) and immunoregulatory-TAM (Reg-TAM), has been refined by single-cell RNA sequencing. In this article, we further discuss how signaling pathways regulate TAM polarization and investigate the multidimensional mechanisms by which TAMs drive PCa progression, the pathways that promote immunotherapy resistance, and the role of macrophage extracellular traps (METs) in PCa metastasis. Targeting TAMs for precision treatment of PCa is a promising therapeutic strategy. These strategies include blocking the adenosine pathway to inhibit SPP1hi-TAMs, reprogramming TAMs with immune checkpoint inhibitors (ICIs) to restore chimeric antigen receptor (CAR)-T cell activity, and novel approaches such as using microRNAs (miRNAs) and natural compounds to modulate TAM polarization. However, these treatment modalities still face challenges, including the complexity of the tumor microenvironment (TME) and TAM heterogeneity, obstacles in drug production and delivery, and toxicity management. This article aims to develop individualized targeting strategies based on the composition, functional status, and signaling dependencies of TAM subpopulations within patient tumors, with the hope of transitioning from a “one-size-fits-all” approach to precision medicine.

Talins, comprising talin-1 (TLN1) and talin-2 (TLN2), are focal adhesion proteins that interact with multiple cytoskeletal components. Often overexpressed in cancers, they regulate integrin activation and cellular adhesion, thereby promoting tumor cell proliferation, invasion, and metastasis. While structurally and functionally similar, TLN1 and TLN2 exhibit distinct biological roles. This review systematically summarizes the current understanding of talin structure, function, and their contributions to tumor progression, highlighting their potential as biomarkers and therapeutic targets in oncology.

Diabetic Bladder Disease (DBD), a common urological complication of diabetes mellitus, severely compromises the quality of life of affected patients. Mitochondria, the primary energy-producing organelles in cells, are closely correlated with the pathogenesis and progression of DBD. As an emerging therapeutic modality, mitochondrial transplantation exhibits substantial potential for the management of DBD. This paper presents a comprehensive review of mitochondrial transplantation, with a focus on its fundamental theories, application conditions, safety profiles, and mitochondrial sources. Subsequently, we explore the association between mitochondrial dysfunction and the pathological mechanisms underlying DBD, analyze the disparities between mitochondrial transplantation and conventional therapeutic approaches, and discuss the prospects of combined and personalized treatment regimens. Finally, this review summarizes the ethical controversies surrounding this therapeutic strategy and outlines future research trends, aiming to lay a theoretical foundation for the development of novel therapeutic modalities against DBD.

BackgroundProstate cancer (PCa) is a common malignant tumor in males, and castration-resistant prostate cancer (CRPC) represents an advanced stage with limited treatment options and poor prognosis. Talin-1 (TLN1) is a cytoskeletal protein implicated in tumor progression, but its specific role and mechanism in CRPC remain unclear.MethodsMass spectrometry (MS) was used to analyze serum peptides from patients with hormone-sensitive prostate cancer (HSPC) and CRPC. TLN1 expression was further validated in clinical prostate tissue samples (59 PCa, 17 benign prostatic hyperplasia) via immunohistochemistry, qPCR, and Western blot. Functional assays (CCK-8, colony formation, wound healing, Transwell) and a nude mouse xenograft model were employed to assess the effects of TLN1 knockdown on CRPC cell lines (DU145, PC3). Transcriptome sequencing, molecular docking, and co-immunoprecipitation (Co-IP) were conducted to explore downstream mechanisms and interactions. Western blot analysis was applied to examine the impact of TLN1 knockdown on apoptosis and the PI3K-AKT, MAPK, and NF-κB signaling pathways in CRPC cell lines. Rescue experiments were performed by knocking down both TLN1 and nerve growth factor receptor (NGFR).ResultsTLN1 expression was significantly upregulated in CRPC patient serum and PCa tissues. Knockdown of TLN1 inhibited proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), promoted apoptosis in CRPC cells, and suppressed tumor growth in vivo. Transcriptome analysis identified NGFR as significantly upregulated upon TLN1 knockdown. TLN1 knockdown can influence the malignant progression of CRPC through the MAPK and PI3K-AKT signaling pathways. Molecular docking and Co-IP confirmed a direct interaction between TLN1 and NGFR. Knockdown of NGFR reversed the tumor-suppressive effects induced by TLN1 silencing.ConclusionsTLN1 inhibits the progression of CRPC by interacting with and regulating the tumor suppressor NGFR. The TLN1/NGFR axis represents a novel potential therapeutic target for CRPC.

Background Accurate preoperative assessment of extracapsular extension (ECE) in prostate cancer is crucial for surgical planning but is limited by inter-reader variability and the poor generalizability of existing models. This study aimed to develop and validate a generalizable deep learning framework based on multiparametric MRI (mpMRI) for automated, cross-center preoperative ECE prediction. Methods This retrospective study included 1044 prostate cancer patients from four centers. We proposed an end-to-end workflow comprising automated prostate segmentation (nnU-Net2) and ECE prediction using a novel Multi-Modal 3D Attention Network (M3A-Net). M3A-Net utilized parallel SEResNet101-based encoders with intra-modal attention and contrastive learning to extract features from multi-modal MRI (T2WI, ADC, DWI). Model discrimination (AUC), calibration (Brier score), and clinical utility (decision curve analysis) were evaluated against five baseline deep learning models under a unified protocol, while inter-cohort differences were analyzed via Mann-Whitney U and chi-squared tests. Results M3A-Net achieved superior discrimination on the internal test set with the highest AUC (0.873 vs. 0.740 for the second-best) and the lowest Brier score (0.151) against five baseline models. It also demonstrated promising generalization on the external validation set (AUC = 0.850), achieving a clinically relevant balance between high sensitivity (0.867) and moderate specificity (0.683). Decision curve analysis suggested that M3A-Net may offer a greater net clinical benefit compared to all five baseline models. Conclusion The proposed M3A-Net framework shows promise for high-precision preoperative ECE prediction with favorable generalization across multi-center data. This model warrants further investigation as a potential tool to assist in surgical planning, thereby potentially improving oncological and functional outcomes.

According to previous studies, the CCR2-V64I polymorphism has been associated with susceptibility to various cancers, yet this relationship remains controversial. To systematically evaluate this association, we conducted a meta-analysis to summarize and validate the available evidence. We comprehensively searched the PubMed, Embase, and Cochrane Library databases and ultimately included 20 case-control studies based on relevance and quality, comprising 4438 cases and 4874 controls. The association strength was analyzed using odds ratios and 95% confidence intervals. Overall analysis revealed a potential association between the CCR2-V64I polymorphism and cancer risk. Subgroup analyses by cancer type indicated that this polymorphism served as a risk factor for oral and bladder cancers, while exerting a protective effect against cervical cancer. Further organ-system-based stratification suggested that this polymorphism was associated with an increased risk of urinary system cancers and head and neck cancers. The results of ethnic subgroup analyses indicated that this polymorphism might be associated with a significantly elevated cancer risk in Caucasian populations. These findings demonstrated that the CCR2-V64I polymorphism may significantly influence cancer susceptibility.

NUPR1 is a pro-tumorigenic factor in bladder cancer (BLCA), but the mechanisms governing its protein stability remain poorly defined. Here, we identified ARIH2 as an E3 ubiquitin ligase that interacts with NUPR1 in BLCA cells through immunoprecipitation-mass spectrometry (IP-MS), co-immunoprecipitation (Co-IP), and immunofluorescence analyses. ARIH2 overexpression reduced NUPR1 abundance and inhibited BLCA cell proliferation and migration while enhancing apoptosis, whereas ARIH2 knockdown increased NUPR1 expression and promoted malignant phenotypes. Mechanistically, ARIH2 depletion prolonged NUPR1 protein stability and reduced its ubiquitination, indicating that ARIH2 negatively regulates NUPR1 through ubiquitin-mediated degradation. Moreover, NUPR1 overexpression suppressed ferroptosis, as reflected by increased GPX4 and SLC7A11, decreased ACSL4, reduced lipid peroxidation, and diminished Fe2+ accumulation, while NUPR1 knockdown exerted the opposite effects. ARIH2 knockdown mimicked the ferroptosis-resistant phenotype induced by NUPR1 upregulation, supporting that ARIH2 modulates ferroptosis through NUPR1. Bioinformatic and experimental analyses further showed that NUPR1 was associated with immunosuppressive infiltration and promoted M2 macrophage polarization. Together, our findings uncover an ARIH2-NUPR1 regulatory axis that drives BLCA progression by suppressing ferroptosis and favouring an immunosuppressive microenvironment, highlighting this pathway as a potential therapeutic target in BLCA.

Prostate cancer (PCa) is a leading malignancy, and progression to castration-resistant prostate cancer (CRPC) remains a central therapeutic challenge. Cuproptosis, a copper-dependent cell death mechanism first characterized in 2022, is triggered by copper binding to lipoylated tricarboxylic acid (TCA)-cycle proteins, inducing their aggregation, Fe-S cluster protein instability, and mitochondrial proteotoxic stress. This review critically evaluates the emerging but still heterogeneous evidence linking cuproptosis to PCa, explicitly distinguishing prostate cancer-specific data from pan-cancer,non-prostate, bioinformatic, and preclinical observations. We describe the core machinery, including ferredoxin 1 (FDX1), dihydrolipoamide acetyltransferase (DLAT), protein lipoylation enzymes, and copper transport/chaperone systems, while emphasizing differences from apoptosis and ferroptosis. In PCa, altered copper homeostasis and mitochondrial metabolic rewiring provide a biologically plausible vulnerability, but current evidence does not yet establish cuproptosis as a validated clinical driver or therapeutic target. We therefore summarize cuproptosis-related gene expression profiles and prognostic models as hypothesis-generating biomarkers, and provide a prostate cancer-specific evidence table that separates bioinformatic, in vitro, in vivo, and clinical levels of support. We also review potential links with metabolic reprogramming, immune microenvironment modulation, PD-L1 regulation, androgen receptor signaling, PTEN/PI3K pathway activity, epigenetic regulation, and crosstalk with ferroptosis. Therapeutically, copper ionophores such as elesclomol and disulfiram/copper, and copper-depleting approaches such as chelators, are discussed as investigational strategies rather than near-clinical solutions. Particular attention is given to toxicity, narrow therapeutic windows, negative or inconclusive clinical data, the absence of validated companion diagnostics in PCa, and the need for patient-selection biomarkers based on copper handling, FDX1/lipoylation status, and mitochondrial dependency. Finally, we outline the experimental and translational studies required before cuproptosis-directed interventions can be rationally tested in advanced PCa.

Background:CD40, a constituent of the tumor necrosis factor (TNF) receptor superfamily, exhibits variable expression across different cancer types. It plays a role in mediating tumor cell proliferation, apoptosis, and survival, as well as antitumor immune responses and the tumor microenvironment. Although some studies have suggested a potential association between CD40 gene polymorphisms and cancer risk, definitive conclusions remain elusive. Methods:We conducted a comprehensive literature search across PubMed, Web of Science, Google Scholar, Embase, and relevant Chinese databases for studies published up to 3 February 2025. Our systematic analysis focused on elucidating the association between CD40 polymorphisms and cancer susceptibility, employing various comparative models and subgroup analyses. We analyzed the differential expression of CD40 between various tumor tissues and their corresponding normal tissues, as well as the impact of CD40 expression levels on the overall survival outcomes of cancer patients using the Gene Expression Profiling Interactive Analysis (GEPIA) database. Based on the NCBI database, we further investigated the distribution characteristics of the mutant allele for four single nucleotide polymorphisms (SNPs) in the CD40 gene across six major global populations. Additionally, we constructed a protein-protein interaction network for CD40 using the STRING database. Results:By analyzing 10 high-quality studies (comprising 20 case-control studies), we illustrate that the specific CD40 gene polymorphism (rs1883832) has a significant impact on breast cancer susceptibility. However, no significant correlation was found between the other three CD40 polymorphisms (rs4810485, rs1800686, and rs3765459) and tumor susceptibility. Conclusion:Our study found a strong association between CD40 polymorphisms (rs1883832) and breast cancer risk. However, a limitation of this study is that it did not explore the potential application of CD40 in the early diagnosis of breast cancer, nor did it clarify its impact on patient prognosis or its feasibility as a biomarker. These critical issues will be key directions for future research.

Testicular cancer is the most frequently diagnosed malignancy in men aged 15–35, predominantly comprising Testicular germ cell tumors (TGCTs). However, less than 5

A novel theranostic radiopharmaceutical targeting prostate-specific membrane antigen (PSMA), [68Ga]Ga/[177Lu]Lu–NYM032, was developed and its diagnostic and therapeutic potential in the treatment of prostate cancer (PCa) was preliminarily evaluated. The diagnostic efficacy of the PET tracer [68Ga]Ga–NYM032 was first evaluated in PSMA-positive xenograft-bearing models (LNCaP models), followed by evaluation in 10 PCa patients using [68Ga]Ga–PSMA617 a comparator. Finally, the therapeutic potential of [177Lu]Lu–NYM032 was evaluated in LNCaP models. [68Ga]Ga/[177Lu]Lu–NYM032 was well-tolerated, and no adverse events were observed in the preclinical and clinical studies. [68Ga]Ga–NYM032 demonstrated PSMA specificity and high radioactive uptake in LNCaP tumors. [68Ga]Ga–NYM032 uptake (SUVmax) did not differ from [68Ga]Ga–PSMA617 uptake in the same in situ lesions at the same p.i. time point (median 9.40 vs. 6.85, P = 0.123, n = 8). Compared with [68Ga]Ga–PSMA617 uptake, [68Ga]Ga–NYM032 uptake was significantly higher in osseous metastases (median 5.10 vs. 3.88, P < 0.001, n = 48), and higher in lymph node metastases (median 7.81 vs. 5.46, n = 2). [177Lu]Lu–NYM032 showed high aggregation in the lesions of LNCaP models and long retention times. [177Lu]Lu–NYM032 could inhibit tumor progression in LNCaP models, and its therapeutic efficiency strengthened with increasing radio-dosage (18.5–74 MBq/mouse). The tumor volume in the high radio-dosage treatment group (74 MBq/mouse) was significantly smaller than that in the blank control group at 21 days p.i. (107.14 ± 13.68 mm3 vs. 1351.86 ± 249.98 mm3, P < 0.001, n = 7). [68Ga]Ga/[177Lu]Lu-NYM032 has considerable potential as a novel and powerful theranostic radiopharmaceutical for PCa. The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT06389695) on 29 Apr, 2024.

Among the myriad of challenges confronting modern medicine, few rival the complexity and persistence of cancer. This disease has long stood as a formidable obstacle to therapeutic innovation. Recently, the emergence of biomimetic materials has heralded a transformative shift in oncology, offering novel strategies for precise drug delivery and integration with advanced technologies such as 3D-printing. In this paper, we begin by categorizing biomimetic materials according to their origins and structural classifications, and subsequently detail their applications in the context of prostate cancer (PCa) treatment. Finally, we provide a comprehensive analysis of the benefits and limitations of these biopolymers, discuss the key barriers hindering their broader application, and propose future research directions to guide progress in this promising domain (Fig. 1).

The tumor microenvironment (TME) is crucial for tumor growth and progression, within which cancer-associated fibroblasts (CAFs) play a central role in regulating cancer cell proliferation, metastasis, and therapy resistance through various mechanisms. Although early-stage prostate cancer (PCa) has a high cure rate, advanced disease often becomes difficult to manage due to resistance to standard therapies such as androgen deprivation therapy (ADT). Therefore, a deep understanding of the interaction mechanisms between CAFs and PCa cells is essential for developing novel therapeutic strategies targeting resistant advanced PCa. This review systematically summarizes key signaling pathways and molecular mechanisms through which CAFs promote PCa progression, as recently discovered, evaluates the potential of CAFs as prognostic biomarkers, and discusses novel CAF-based therapeutic targets and intervention strategies for PCa.

Prostate cancer (PCa) is the second most common cancer in men worldwide. Protein arginine methyltransferase 7 (PRMT7) expression is associated with tumor growth, as it can drive tumor cell proliferation and promote its invasiveness in several types of cancer. However, its mechanism in PCa remains to be elucidated. In the present study, the function and associated mechanism of PRMT7 in PCa cells were investigated. The relationship between PRMT7 and PCa was analyzed using The Cancer Genome Atlas online database. Tissue chip techniques were used to identify the clinical relevance of PRMT7 expression. PRMT7 expression levels in PCa tissues and cells were verified using reverse transcription-quantitative PCR (RT-qPCR). Cell cycle, migration, proliferation and apoptosis of PC3 and DU145 cells were observed using flow cytometry, Cell Counting Kit-8, wound healing, plate cloning and cell invasion assays. Gene set enrichment analysis and chip expression profiles were used to predict the potential signaling pathway involved in the action of PRMT7 in PCa. First, The Cancer Genome Atlas database, tissue microarray analysis and RT-qPCR revealed that PRMT7 expression was increased in PCa tissues and cells. Furthermore, small interfering RNA-mediated PRMT7 knockdown led to a notable reduction in the proliferation of cells, increased apoptosis, affected the cell cycle and decreased cell migration and invasion. Furthermore, PRMT7 regulated the functions of Yin Yang 1 (YY1), tumor protein p53 (TP53), cyclin D2 (CCND2), CDK6 and retinoblastoma 1 (RB1) in PCa. PRMT7 may promote proliferation, migration and metastasis in PCa cells by regulating the activity of YY1, TP53, CCND2, CDK6 and RB1 in the cell cycle signaling pathway.

BackgroundProstate cancer (PCa) is a heterogeneous disease affecting over 14% of the male population worldwide. Although patients often respond positively to initial treatments within the first 2-3 years, many eventually develop a more lethal form of the disease known as castration-resistant PCa (CRPC). At present, no biomarkers that predict the onset of CRPC are available. This study aims to provide insights into the diagnosis and prediction of CRPC emergence.MethodsProtein expression dynamics were analysed in drug (androgen receptor inhibitor)-tolerant persister (DTP) and drug withdrawal cells using proteomics to identify potential biomarkers. These biomarkers were subsequently validated using a mouse model, 180-paired carcinoma/benign tissues, and 482 serum samples. Five machine learning algorithms were employed to build clinical prediction models, wherein the SHapley Additive exPlanation (SHAP) framework was used to interpret the best-performing model. Moreover, three regression models were developed to determine the Time from initial PCa diagnosis to CRPC development (TPC) in patients.ResultsWe identified that the protein expression levels of GPX4, NDUFS4, PRDX5, and TXNRD2 were significantly upregulated in PCa patients, particularly in those with CRPC. Among the tested machine learning models, the random forest and extreme gradient boosting models performed best on tissue and serum cohorts, achieving AUCs of 0.958 and 0.988, respectively. In addition, a significant inverse correlation was observed between TPC and serum levels of these four biomarkers. This correlation was formulated in three regression models, which achieved the smallest mean absolute error of 1.903 on independent datasets for predicting CRPC emergence.ConclusionOur study provides new insights into the role of DTP cells in CRPC development. The quad protein panel identified in our study, along with the post hoc and intrinsically explainable prediction models, may serve as a convenient and real-time prognostic tool, addressing the current lack of clinical biomarkers for CRPC.

We here investigate the expression of the mitochondrial carrier homolog 2 (MTCH2) and its potential function in castration-resistant prostate cancer (CRPC). Bioinformatic analyses reveal that MTCH2 overexpression is associated with critical clinical parameters of prostate cancer. Single-cell sequencing data indicate elevated MTCH2 expression in the prostate cancer epithelium. MTCH2 is also upregulated in locally treated CRPC tissue and various primary human CRPC cells. Using genetic silencing via shRNA and knockout (KO) through the CRISPR-sgRNA approach, we showed that the depletion of MTCH2 impaired mitochondrial function, resulting in a reduced oxygen consumption rate, diminished complex I activity, and decreased ATP levels, mitochondrial depolarization, and increased reactive oxygen species production in primary CRPC cells. The silencing or KO of MTCH2 significantly inhibited cell viability, proliferation, and migration, together with a marked increase in apoptosis in the primary CRPC cells. In contrast, ectopic expression of MTCH2 provided CRPC cells with pro-tumorigenic properties, enhancing ATP production and promoting cell proliferation and migration. MTCH2 silencing also markedly inhibited the growth of subcutaneous xenografts of the primary CRPC cells in nude mice. The MTCH2-silenced xenografts exhibited increased apoptosis, elevated lipid peroxidation, and decreased ATP levels. These results provide new insights into the role of MTCH2 in supporting mitochondrial function and CRPC progression.

Post-prostatectomy urinary incontinence (PPUI) is a common complication for patients with prostate cancer after surgery. MicroRNA-330-3p (miR-330-3p) is down-regulated in stress urinary incontinence patients. However, its clinical role and regulatory mechanism in PPUI remain unknown. To assess the clinical significance of miR-330-3p in PPUI and to explore the potential mechanisms via matrix metalloproteinase 2 (MMP2) regulation. This study enrolled 135 ageing prostate cancer patients (86 without PPUI, 49 with PPUI). Reverse transcription PCR (RT-qPCR) was utilized to measure the levels of miR-330-3p, while Receiver operating characteristic (ROC) analysis was conducted to evaluate the predictive significance of miR-330-3p for PPUI. The proliferative of human urethral fibroblasts (HUFs) was assessed by Cell Counting Kit-8 (CCK-8) assay, while inflammatory cytokines were quantified via enzyme-linked immunosorbent assay (ELISA) kits. Western blot assay was employed to examine the protein levels of extracellular matrix (ECM) remodeling-related markers. The miR-330-3p/MMP2 interaction was validated by dual-luciferase assay. miR-330-3p was significantly downregulated in PPUI patients, with low expression predicting PPUI. In HUFs, miR-330-3p overexpression inhibited IL-1β-induced hyperproliferation, inflammation, and ECM degradation. Overexpression of MMP2 counteracted the influence of miR-330-3p mimic on HUFs. miR-330-3p is a potential biomarker for PPUI and regulates the function of urethral fibroblasts by targeting MMP2.

BACKGROUND:While there is a growing volume of evidence suggesting that relatively prevalent functional polymorphisms present within apoptosis-related genes may influence human prostate cancer (PCa) susceptibility, the clinical relevance of these findings remains inconclusive. AIMS:This meta-analysis was thus developed with the goal of generating more precise estimates of the relationships between polymorphisms in four apoptosis-associated genes (NKX3-1, caspase-3, caspase-9, and BCL-2) and the risk of PCa. METHODS AND RESULTS:The PubMed, Web of Science, Google Scholar, Embase, Cochrane Library, and SinoMed (CNKI and Wanfang) databases were searched for relevant studies published through December 20, 2023, using the following keywords: "polymorphism" or "variant" and "carcinoma" or "cancer" or "tumor" and "NKX3-1," "CASP3" or "Caspase-3," "CASP9" or "Caspase-9," "BCL-2" or "B-cell lymphoma" and "prostate cancer" or "PCa" or "prostate adenocarcinoma." This approach led to the identification of 22 case-control studies related to the association between apoptosis-related gene polymorphisms and PCa susceptibility enrolling 9706 cases and 12 567 controls. Subsequent analyses revealed that the NKX3-1 rs2228013, CASP9 rs1052571, and CASP9 rs4645982 polymorphisms were associated with greater PCa risk, whereas the CASP3 rs4647603 polymorphism was associated with a risk reduction. CONCLUSION:These findings provide strong evidence for the potential contributions of polymorphisms in the apoptosis-related caspase-3, caspase-9, and NKX3-1 genes in the onset and progression of PCa.

Tropomyosin 3 (TPM3), one of the four tropomyosin genes, is predominantly expressed in eukaryotic cells. As a crucial regulatory protein, TPM3 associates with actin within thin myofilaments, thereby playing an essential role in the regulation of muscle contraction. Beyond its fundamental function in muscle physiology, TPM3 is implicated in oncogenesis. This review elucidates the molecular mechanisms underpinning TPM3 gene fusions, delineates the tumor types associated with these fusions, and examines their clinical implications. Gene fusions such as TPM3—NTRK1, TPM3—ALK, and TPM3—ROS1 have been identified as oncogenic drivers in various cancers. These fusions promote constitutive activation of tyrosine kinases, disrupt normal cellular signaling, and consequently accelerate tumorigenesis. Malignancies harboring TPM3 fusions encompass several tumor categories. With the advent of tyrosine kinase inhibitors (TKIs) targeting NTRK1, ALK, and ROS1 fusions, these rearrangements have gained significant therapeutic relevance. However, resistance mechanisms and tumor heterogeneity pose ongoing challenges to targeted therapy. By synthesizing current evidence, this review aims to provide insights into the diagnostic, prognostic, and therapeutic landscape of TPM3—related gene fusions, fostering advancements in precision oncology.