Molecular Cancer最新文献

{"title":"HPGD induces ferroptosis and autophagy to suppress esophageal squamous cell carcinoma through the LXA4–ERK1/2–U2AF2–TFRC axis","authors":"Tianyun Ma, Xiamei Guo, Jueying Zhao, Chenlong Wang, Xiaojuan Yu, Rongliang Mo, Zhuoying Han, Lulu Feng, Longfei Liu, Weiyong Yu, Fangyi Xu, Li Zhang, Qilong Wang, Chao Luo","doi":"10.1186/s12943-025-02464-x","DOIUrl":"https://doi.org/10.1186/s12943-025-02464-x","url":null,"abstract":"Although 15-hydroxyprostaglandin dehydrogenase (HPGD) is known to regulate the metabolism of prostaglandins and lipoxin A4, and its dysregulation has been implicated in various cancers, its role in esophageal squamous cell carcinoma (ESCC) has not been determined. This study is the first to comprehensively characterize HPGD expression in ESCC and establish its clinical relevance in predicting patient outcomes. Furthermore, we elucidated the previously unrecognized molecular mechanisms through which HPGD suppresses ESCC progression and its potential as a novel therapeutic target. Transcriptome sequencing was performed on paired tumor and adjacent normal tissues from deceased patients with ESCC to identify differentially expressed genes. The differential expression of the HPGD gene was subsequently validated in two independent, large-scale ESCC patient cohorts, and its prognostic significance was evaluated. To evaluate the functional role of HPGD in ESCC, the enzyme was overexpressed in ESCC cell lines, and a series of in vitro assays were conducted to assess its effects on proliferation, apoptosis, invasion, and migration. To elucidate the molecular mechanisms underlying the effects of HPGD, we performed transcriptomic sequencing to profile gene expression changes in ESCC cells. Through multiple analyses, including measurements of lipid peroxidation, intracellular ferrous ion and reactive oxygen species (ROS) levels, dual-fluorescence flow cytometry for autophagy, phosphoprotein microarrays, biotin pull-down assays, and chromatin immunoprecipitation (ChIP), we demonstrated that HPGD regulates the malignant phenotype of ESCC cells primarily by inducing ferroptosis and autophagy. Finally, the impact of HPGD on ESCC tumor growth was validated in vivo using a subcutaneous xenograft model in nude mice. HPGD expression was significantly lower in ESCC tissues than in normal tissues and was negatively correlated with tumor cell differentiation and patient outcomes. HPGD overexpression inhibited ESCC cell proliferation, invasion, and migration in vitro and in xenograft tumor growth in vivo. In vitro experiments demonstrated that HPGD suppresses ERK1/2 activation by facilitating lipoxin A4 (LXA4) degradation. This inhibition facilitates binding of the RNA-binding protein U2AF2 to the promoter region of the transferrin receptor (TFRC), thereby increasing TFRC expression. Consequently, these alterations lead to intracellular iron accumulation and initiate ferroptosis. Excessive generation of ROS during ferroptosis results in hyperactivation of autophagy via the AMPK/mTOR signaling pathway. Mitigating the HPGD-induced upregulation of TFRC or reducing ROS production effectively reverses ferroptosis, prevents excessive autophagy, and ameliorates malignant cell phenotypes. HPGD exerts its antitumor effects by promoting ferroptosis through the LXA4-ERK1/2-U2AF2 signaling axis, which in turn induces autophagy hyperactivation via the AMPK-mTOR pathway. These finding","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"28 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of TAS-102 plus Surufatinib in third and later line metastatic pancreatic cancer: a prospective, single center and biomarker exploratory, phase II study","authors":"Yunxin Lu, Qingguang Lin, Yongxin Mo, Furong Liu, Mengwei Zhang, Runjie Huang, Yun Wang, Yinnan Wang, Zhiqiang Wang, Huiyan Luo, Guifang Guo, Jianwen Chen, Yu Liu, Mingming He, Fenghua Wang, Feng Wang, Dongsheng Zhang","doi":"10.1186/s12943-025-02437-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02437-0","url":null,"abstract":"Metastatic pancreatic cancer (mPC) has a dismal prognosis, with first line systemic therapy relying primarily on FOLFIRINOX (5FU/irinotecan/oxaliplatin) or AG (Gemcitabine/Nab-Paclitaxel). Therapeutic options for mPC refractory to these regimens remain poorly defined, and data on later-line options are scarce. This prospective, single-arm study evaluated the safety and preliminary efficacy of combining the anti-angiogenic agent surufatinib with the cytotoxic drug TAS-102 (Trifluridine/Tipiracil) in mPC patients who had progressed on ≥ 2 prior lines of therapy. mPC patients who were refractory to at least 2 previous regimens were enrolled and received TAS-102 (35 mg/m2, po, bid, D1-D5, D8-D12) plus surufatinib (250 mg, po, qd) in a 4-week cycle. The tumor response was assessed by the researcher every 8 weeks and treatment continued until disease progression, unacceptable toxicity, investigator discretion, or patient withdrawal of informed consent. Primary and secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Between January 2023 and June 2024, 22 patients were enrolled into this study. Among 20 patients analyzed for efficacy, median PFS was 2.35 months (95% CI: 1.91–3.94) and median OS was 6.34 months (95% CI: 3.81–10.09). The ORR and DCR were 20% (4/20; all partial response) and 30% (6/20), respectively. All patients experienced treatment emergent adverse events (TEAEs), with anemia (59.1%), neutropenia (54.6%), leukocytopenia (50.0%), and lymphocytopenia (45.5%) as the most common any-grade events. Grade ≥ 3 TEAEs including neutropenia (31.8%), lymphocytopenia (13.6%), and anemia (9.1%), were observed in 50.0% (11/22) of patients. Subgroup analysis identified metastases involving > 2 organs or hepatic sites as potential predicative biomarkers for inferior efficacy. Proteomic screening revealed that overexpressed OCIAD2 correlated with poor prognosis, a finding validated in two publicly available external cohorts (CPTAC database and RuiJin cohort). Combination of TAS-102 and surufatinib demonstrates clinically meaningful efficacy and manageable toxicity as therapeutic option for later-line mPC. The biomarkers identified in this study may hold the potential to guide patient stratification and warrant further investigation to optimize precision application of this regimen. This study was prospectively registered at clinicaltrials.gov with the number NCT05481463 on August 1st 2022.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"92 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer","authors":"Fu-Ying Zhao, Li-Ye Shi, Lu-Jiao Yu, Si-Qi Wang, Chu-Yao Sun, Na Zhang, Hua-Qin Wang","doi":"10.1186/s12943-025-02433-4","DOIUrl":"https://doi.org/10.1186/s12943-025-02433-4","url":null,"abstract":"Radiotherapy resistance remains a major clinical challenge, largely driven by tumors’ ability to dynamically adapt through complex molecular networks. Critically, the ubiquitin system has emerged as a critical regulator of this resistance. This review examines how the ubiquitin system orchestrates radiotherapy resistance through spatiotemporal control of DNA repair fidelity, metabolic reprogramming, and immune evasion. We explore how the ubiquitin code, defined by its chain topology diversity (such as K48-linked proteolysis versus K63-mediated signaling) and crosstalk with phosphorylation, SUMOylation, and acetylation, generates diverse resistance mechanisms. These mechanisms, however, also present vulnerabilities exploitable for radio-sensitization. Notably, monoubiquitylation of both histone and non-histone protein collaboratively modulates chromatin dynamics and DNA damage responses to maintain genome integrity during radiation. Furthermore, ubiquitination critically regulates caner metabolism, reprogramming processes such as ferroptosis susceptibility, hypoxia adaptation, and nutrient flux, thereby creating targetable vulnerabilities for radio-sensitization. While targeting key E3 ligases and deubiquitinases (DUBs) shows preclinical promise, clinical translation faces obstacles including functional redundancy, unintended on-target toxicity, and adaptive tumor responses. Distinct from other post-translational modifications (PTMs), the ubiquitin system offers unique clinical advantages: its dynamic reversibility, chain topology diversity, and recent breakthroughs in targeted degradation (e.g., PROTACs) enable precise disruption of radioresistance networks. By integrating these mechanistic insights with biomarker-guided therapeutic strategies, ubiquitin-targeting agents are emerging as fundamental components of next-generation radiotherapy protocols.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"10 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0038737 promotes PARPi resistance in castration-resistant prostate cancer via IGF2BP3-mediated DNPH1 mRNA stabilization","authors":"Zhongyuan Wang, Qintao Ge, Aihetaimujiang Anwaier, Shiwei Liu, Xi Tian, Zihao Zhang, Tao Feng, Zhe Hong, Dingwei Ye, Wenhao Xu, Xiaojian Qin","doi":"10.1186/s12943-025-02447-y","DOIUrl":"https://doi.org/10.1186/s12943-025-02447-y","url":null,"abstract":"Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) poses a major challenge to therapeutic efficacy in castration-resistant prostate cancer (CRPC). Although circular RNAs (circRNAs) have emerged as critical regulators in cancer biology, their involvement in PARPi resistance remains largely uncharacterized. This study aims to elucidate the molecular mechanism by which hsa_circ_0038737 modulates PARPi resistance in CRPC through post-transcriptional regulatory pathways. We employed a comprehensive set of in vitro and in vivo approaches, including qRT-PCR, RNA sequencing, RNA-protein pull-down, RNA immunoprecipitation, functional assays, and xenograft/organoid models, to investigate the biological function and mechanistic role of hsa_circ_0038737 in CRPC progression and therapeutic response. We identified hsa_circ_0038737 as a nuclear-enriched circRNA significantly upregulated in CRPC, with expression levels correlating with poor prognosis and aggressive clinical features. Mechanistically, hsa_circ_0038737 interacts with RNA-binding protein (RBP) IGF2BP3, enhancing the stability of DNPH1 mRNA, a nucleotide sanitizer critical for DNA repair. The circRNA-RBP-mRNA regulatory axis promotes PARPi resistance by facilitating DNA damage repair capacity. Moreover, we revealed that reverse-complementary Alu elements mediate circRNA biogenesis, with HNRNPDL facilitating this process. Pharmacologic inhibition of DNPH1 effectively restored PARPi sensitivity both in vitro and in vivo. Our findings reveal a novel hsa_circ_0038737/IGF2BP3/DNPH1 axis driving PARPi resistance in CRPC, offering promising potential biomarkers and therapeutic targets to overcome resistance and improve treatment outcomes in advanced prostate cancer.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"43 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming cellular senescence and aging clocks for advanced cancer immunotherapy","authors":"Huiting Yang, Dong Liu, Liewang Qiu, Rui Wang, Chuchu Zhang, Danqing Yu, Qingping Zhong, Nitta Yuki, Zhentao Song, Taotao Zhu, Haixing Ju, Weifeng Hong, Ji Zhu","doi":"10.1186/s12943-025-02459-8","DOIUrl":"https://doi.org/10.1186/s12943-025-02459-8","url":null,"abstract":"Cellular senescence has gradually been recognized as a key process, which not only inhibits the occurrence of early tumors but also promotes advanced malignant progression through secretory and immunomodulatory functions. Initially, cellular senescence manifested as irreversible cell cycle arrest, but now it encompasses a broader phenotype regulated by the p53-p21CIP1 and p16INK4A-Rb pathways. Although secretory phenotypes related to aging can recruit immune effectors to clear new tumor cells, persistent senescent cell populations often trigger chronic inflammation, promoting immune escape and fibrosis. In this review, we first discuss the molecular underpinnings of cellular senescence, highlighting its induction pathways and diverse physiological or pathological roles. We then examine the composition of the tumor microenvironment, where senescent cells accumulate and secrete pro-inflammatory cytokines, reshaping immune surveillance and extracellular matrix architecture. Against this backdrop, we explore how aging clocks refine our understanding of individual susceptibility to malignancy by distinguishing biological from chronological aging. We also present current therapeutic prospects, including senolytic agents targeting senescent stromal cells that promote tumor growth, and the utilization of aging clock metrics to tailor immunotherapies more effectively for older patients. Finally, we consider the major challenges facing clinical translation, from standardizing multi-omics data pipelines to clarifying the ethical implications of measuring biological age. By bridging senescence biology with geroscience and cutting-edge oncology, we posit that aging clocks may catalyze a transformation in cancer care, enabling more personalized, effective, and age-conscious treatment strategies.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"7 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome-metabolome interplay in pancreatic cancer progression: insights from multi-omics analysis","authors":"Dong Luo, Qizhen Chen, Yixiong Li, Jianbo Yang, Yongguang Tao, Liandong Ji, Xuejun Gong","doi":"10.1186/s12943-025-02458-9","DOIUrl":"https://doi.org/10.1186/s12943-025-02458-9","url":null,"abstract":"Recent studies suggest that intratumoral microbiome and altered metabolic networks play crucial roles in pancreatic cancer (PC) progression. However, the precise interplay between microbial communities and tumor metabolism in PC remains poorly understood. This study aims to investigate the impact of the intratumoral microbiome, the metabolic landscape, and their interactions on PC development. 16S rDNA sequencing and Untargeted metabolomic profiling were performed on 47 paired pancreatic cancer and adjacent normal tissues to analyze their intratumoral microbiome and metabolic landscapes. Bioinformatics tools were used to conduct differential microbiome abundance analysis and pathway enrichment. A correlation analysis was performed to identify key microbiota-metabolite interactions. 16S rDNA sequencing revealed significant differences in the abundance and diversity (α-diversity and β-diversity) of the intratumoral microbiome in PC. The predominant species in pancreatic cancer were Pseudomonas. Enrichment analysis showed that amino acid metabolic pathways, including Arginine and Proline Metabolism, Arginine Biosynthesis, were significantly enriched in PC. Untargeted metabolomics identified 298 metabolites that were significantly altered in PC (fold change > 1.5, P-value < 0.05). These included amino acid metabolites such as Lys-Leu, Pro-Leu, Arg-Leu, Lys-Val, His-Lys, and others. Functional enrichment analysis highlighted several metabolic pathways that play important roles in pancreatic cancer, including Glycine, Serine, and Threonine Metabolism, Amino Acid Biosynthesis, Metabolic Pathways and Cysteine and Methionine Metabolism. Correlation analysis between microbiome and metabolic data revealed significant associations between Pseudomonas and several metabolites, including Alpha-ketoisovaleric acid, 16-hydroxyhexadecanoic acid, Myristic acid, Nonanoic acid (the Spearman correlation coefficient r, 0.5 ≤|r|≤ 1 and P-value < 0.05). This study suggests a relationship between the microbiome and metabolism in pancreatic cancer. We observed that Pseudomonas contributes to altered amino acid metabolism, but whether this interaction is causal and the mechanisms underlying it remain unclear. Further experimental validation is required before considering microbiome-targeted metabolic interventions as viable therapeutic strategies.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"75 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid reprogramming and ferroptosis crosstalk in clear cell renal cell carcinoma: metabolic vulnerabilities and therapeutic targeting","authors":"Qing Deng, Yu Ji, Jian Liu, Tao Wen","doi":"10.1186/s12943-025-02457-w","DOIUrl":"https://doi.org/10.1186/s12943-025-02457-w","url":null,"abstract":"Clear cell renal cell carcinoma (ccRCC) features metabolic dysregulation, with altered lipid metabolism and ferroptosis dysregulation driving malignancy. This review examines the interplay between lipid reprogramming and ferroptosis resistance in ccRCC pathogenesis and therapy. Tumor cells exploit lipid accumulation for growth and evade ferroptosis adaptively. Preclinical studies show targeting lipid metabolism or inducing ferroptosis synergizes with anti-angiogenic/immunotherapy, improving survival. This study provides a framework for dual therapeutic strategies.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"109 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of acetylcholine and its receptors in tumor immune regulation: mechanisms and potential therapeutic targets","authors":"Chunyu Zhang, Xiangdong Guo, Yanan Wang, Shuo Zhang, Zhihua Wang","doi":"10.1186/s12943-025-02441-4","DOIUrl":"https://doi.org/10.1186/s12943-025-02441-4","url":null,"abstract":"Acetylcholine (ACh) is an essential neurotransmitter that has recently gained attention for its multifunctional role in tumor immune regulation. By binding neuronal loss to nicotinic and muscarinic receptors, ACh directly promotes tumor cell proliferation and migration while modulating immune cell functions, thereby influencing the tumor microenvironment. Additionally, ACh plays a crucial role in tumor angiogenesis and stromal remodeling. Recent studies suggest that combining ACh modulators with immune checkpoint inhibitors and other therapies may improve treatment efficacy and overcome resistance. This review highlights current research developments regarding ACh in tumor immune regulation, explores its underlying mechanisms and clinical potential, and provides a theoretical basis for developing personalized therapeutic strategies.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"4 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic modification of cuproptosis by non-coding RNAs in cancer drug resistance","authors":"Fei Du, Lu Tang, Fang Wang, Xian Jiang, Junxin Li, Guojun Wang, Zhuo Zhang","doi":"10.1186/s12943-025-02434-3","DOIUrl":"https://doi.org/10.1186/s12943-025-02434-3","url":null,"abstract":"Tumor drug resistance remains a significant barrier to effective cancer treatment, undermining the clinical efficacy of current therapies through adaptive and evolving mechanisms. Cuproptosis, a recently discovered form of programmed cell death, emerges as a promising tumor suppressor by targeting mitochondrial metabolic pathways, offering a novel strategy to combat drug resistance. However, targeting mitochondrial metabolism presents challenges due to the essential physiological roles of mitochondria in normal tissues, raising concerns about potential on-target toxicity. Recent studies have revealed the dynamic role of non-coding RNAs (ncRNAs) in modulating susceptibility to cuproptosis via epigenetic alterations, potentially serving as key factors in therapeutic response. In this review, we first summarize the complex interplay between chemotherapeutic resistance and cancer progression/relapse. Then, we outline the key molecular mechanisms underlying cuproptosis, its upstream epigenetic regulators, and the downstream effects on drug resistance. Finally, this review discusses the latest findings on how ncRNAs influence resistance to chemotherapy, immunotherapy, and targeted therapy by modulating cuproptosis. This review aims to untangle the regulatory mechanisms of ncRNA-mediated epigenetic modifications on cuproptosis, highlighting the critical role of the ncRNA-cuproptosis interaction network in tumor drug resistance progression. These insights provide a conceptual foundation for developing ncRNA-targeted therapies in conjunction with cuproptosis-inducing approaches.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"76 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional gold nanoparticles: bridging detection, diagnosis, and targeted therapy in cancer","authors":"Lianting Zhuang, Yi Lian, Tiantong Zhu","doi":"10.1186/s12943-025-02431-6","DOIUrl":"https://doi.org/10.1186/s12943-025-02431-6","url":null,"abstract":"Cancer remains a leading global health challenge, responsible for millions of deaths annually. Conventional therapies are hindered by systemic toxicity, drug resistance, and ineffective targeting of the tumor microenvironment (TME). Gold nanoparticles (AuNPs) have emerged as promising tools in oncology, offering unique plasmonic properties, high biocompatibility, and the ability to be engineered for multifunctional applications. Recent advancements include sustainable biogenic synthesis methods, precision targeting through ligands, aptamers, and peptides, and the development of theranostic platforms that integrate multimodal imaging with controlled drug and gene delivery. Additionally, AuNPs are being combined with therapies like photothermal-immunotherapy to remodel the TME, enhancing therapeutic efficacy. This review explores AuNP applications in cancer detection, diagnosis, and therapy, focusing on targeted drug/gene delivery to overcome chemoresistance, advanced biosensing tools for early detection, hybrid nanocarrier designs for TME penetration, and combinatorial platforms for integrating photodynamic, chemotherapy, and radiotherapy. It also addresses key translational barriers, such as protein corona dynamics, long-term biodistribution concerns, and the scalability of green synthesis methods. To facilitate clinical adoption, it emphasizes the need for GMP-compatible manufacturing, personalized nanomedicine through computational design, and standardized safety assessments. AuNPs represent a transformative approach to precision oncology, with the potential to integrate diagnostic and therapeutic functions into adaptable, real-time systems. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"27 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}