Cancer Cell International最新文献

{"title":"Exosomal circPOLK promotes metastasis of NSCLC cells via regulating mir-1204/SOX8 axis.","authors":"Yang-Ling Li, Ye-Han Liu, Jing Cheng, Zhen-Qiang Wei, Neng-Ming Lin, Chong Zhang","doi":"10.1186/s12935-026-04306-2","DOIUrl":"https://doi.org/10.1186/s12935-026-04306-2","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and the prognosis of NSCLC patients is still poor particularly for patients with metastatic disease. Thus, extending the knowledge about the mechanism of metastasis is critical for NSCLC treatment. We demonstrated that hsa_circ_0073052 (circPOLK) was overexpressed in blood exosomes from cancer patients than those from healthy people. CircPOLK overexpression enhanced the metastasis and EMT progression of NSCLC cells. Next, circPOLK might function as miRNA sponge in NSCLC cells. Through bioinformatical prediction and RNA pull-down experiment, miR-1204 might be a potential target of circPOLK. Interestingly, serumal miR-1204 was an efficacious diagnostic and prognostic molecular for lung cancer patients and acted as a suppressor on NSCLC progression. Furthermore, circPOLK promoted metastasis of NSCLC via regulating miR-1204. Furthermore, SOX8 was identified as a potential target of circPOLK/miR-1204. GO enrichment of circPOLK regulated DEGs showed that circPOLK might be involved in angiogenesis of NSCLC. Indeed, circPOLK secreted by NSCLC cells could promote angiogenesis. Our dada not only identifies a novel circPOLK/miR-1204/SOX8 signaling pathway, but also provides therapeutical strategies for NSCLC patients with metastatic disease.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis of the mechanism by ATP13A2 regulates the tumor microenvironment and prognosis in hepatocellular carcinoma.","authors":"Yijie Weng, Changan Chen, Yueqing Cai, Feifei Gao, Jiahua Situ, Jiajian Wu, Guixia Zhang, Xintian Chen, Danxian Jiang","doi":"10.1186/s12935-026-04315-1","DOIUrl":"https://doi.org/10.1186/s12935-026-04315-1","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatocellular carcinoma (HCC) is a prevalent global cancer. Most patients with HCC are diagnosed at an advanced stage. Therefore, new biomarkers and treatments are urgently needed.</p><p><strong>Methods: </strong>We employed eQTL and intersected the results with aging-related genes, ultimately identifying ATP13A2 as the target gene for our study. The expression and intercellular communication of ATP13A2 in HCC were analyzed using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics sequencing (stRNA-seq). Subsequently, we utilized the Deep Learning Survival Neural Network (DeepSurv) model to construct a prognostic model. Additionally, we performed RNA sequencing (RNA-seq) analysis. In vitro, CCK8, cell wound healing, and flow cytometry assays were used to identify the potential functions of ATP13A2 in HCC cells.</p><p><strong>Results: </strong>ATP13A2 is positively associated with HCC risk. scRNA-seq analysis demonstrated that ATP13A2 + malignant cells exhibited stronger interactions with tumor microenvironment (TME) cells. stRNA-seq analysis revealed that ATP13A2 + malignant cells were significantly spatially correlated with TME cells. The DeepSurv prognostic model indicated that HCC patients with high risk scores had a significantly lower survival rate than those with low risk scores. In vitro, knockdown of ATP13A2 affected the proliferation, apoptosis, and migration of HCC cells.</p><p><strong>Conclusion: </strong>The ATP13A2 gene is closely related to TME, and its high expression is indicative of poor prognosis. ATP13A2 has the potential to serve as a biomarker for prognosis and efficacy assessment of HCC and may offer a new therapeutic target for its treatment.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAK inhibitor suppresses ovarian cancer growth by inhibiting tumor angiogenesis.","authors":"Jingtian Shen, Zhiru Su, Yihan Shan, Ying Wang, Yi Meng, Zhiling Li, Shuping Miao, Jinyi Zhang, Xiaojian Yan","doi":"10.1186/s12935-026-04325-z","DOIUrl":"https://doi.org/10.1186/s12935-026-04325-z","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer, the second deadliest gynecological malignancy, necessitates the identification of novel therapeutic targets. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, has emerged as a promising target for ovarian cancer treatment owing to its diverse regulatory roles. While existing research has demonstrated FAK's role in tumor progression and angiogenesis, substantial knowledge gaps remain concerning the precise mechanisms through which FAK inhibitors hinder tumorigenesis and their specific roles in anti-angiogenic processes.</p><p><strong>Methods: </strong>This study utilized bioinformatics analysis to examine FAK expression in ovarian cancer, with validation performed using clinical samples from platinum-sensitive and platinum-resistant patients. The anti-tumor effects of FAK inhibitors were investigated through in vitro and in vivo experiments. Human induced pluripotent stem cells (hiPSCs) were differentiated into endothelial cells to facilitate vascular research. Pharmacological inhibition and genetic knockdown techniques were employed to study FAK's role in angiogenesis, followed by functional assays to analyze specific angiogenesis processes.</p><p><strong>Results: </strong>Bioinformatics analysis identified increased FAK expression in ovarian cancer tissues, which was significantly associated with poor prognosis. Clinical specimens confirmed higher levels of total FAK and pY397 FAK in platinum-resistant cancers compared to sensitive counterparts. In vivo experiments, including laser speckle contrast imaging and CD31 immunofluorescence, demonstrated that FAK inhibitors suppress tumor angiogenesis. Both pharmacological and genetic approaches revealed a pivotal regulatory function of FAK in angiogenesis. FAK inhibition appeared particularly effective in disrupting endothelial sprouting processes across the tested models.</p><p><strong>Conclusions: </strong>The results provide compelling experimental evidence supporting FAK inhibitors as potential targeted therapeutic agents for ovarian cancer. Our findings suggest that the anti-tumor effects of FAK inhibitors are closely associated with the suppression of tumor angiogenesis, which may be attributed to the potent inhibitory impact of FAK blockade on endothelial sprouting. This reveals a distinct mechanism of action that differs from traditional cytotoxic agents.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analyses reveal a potential role for PFKFB4 in M2 macrophage polarization and hepatocellular carcinoma progression.","authors":"Siying Wang, Qinqiu Zhang, Tian Li, Zibo Xu, Zhaoxia Wang, Xuyu Chen, Chen Chen Wei","doi":"10.1186/s12935-026-04326-y","DOIUrl":"https://doi.org/10.1186/s12935-026-04326-y","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is the third most lethal malignant tumor worldwide, PFKFB4 has emerged as a key metabolic enzyme with critical roles in cancer progression and immune regulation. However, its precise role in hepatocellular carcinoma remains unclear.</p><p><strong>Methods: </strong>In this study, we performed integrated analyses, including single-cell transcriptomics, bioinformatics, enrichment analysis, in vitro functional assays, and in vivo validation, to explore the role of PFKFB4 in HCC progression and its influence on macrophage polarization.</p><p><strong>Results: </strong>Single-cell transcriptomic analysis identified elevated PFKFB4 expression in macrophages, correlating significantly with M2 polarization markers. Functional assays demonstrated that knockdown of PFKFB4 suppressed HCC cell proliferation, migration, and promoted apoptosis, while its overexpression exhibited the opposite effects. Mechanistically, inhibition of PFKFB4 reduced activation of the MEK/ERK signaling pathway, suggesting this pathway as a potential mediator. Additionally, Co-culture experiments revealed that knockdown of PFKFB4 in tumor cells led to a reduced M2 polarization of macrophages, suggesting its role in immune modulation.</p><p><strong>Conclusion: </strong>Collectively, our findings indicate that PFKFB4 drives hepatocellular carcinoma progression through activation of the MEK/ERK signaling pathway and, in parallel, influences tumor progression via tumor cell-mediated modulation of M2 macrophage polarization.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico screening, synthesis, and biological evaluation of pyrazolopyrimidine-derived mTOR inhibitors for anticancer and senomorphic effects.","authors":"David Rysanek, Zofia Chrienova, Dorota Stary, Marek Bajda, Josef Novak, Pavla Vasicova, Jirina Kroupova, Rudolf Andrys, Adam Skarka, Erika Rousarova, Jan Capek, Tomas Rousar, Zoran Milovanovic, Jelica Grujic-Milanovic, Vesna Jacevic, Jayaprakash N Kolla, Martin Popr, Dominika Maurencova, Patrik Oleksak, Lukas Fresser, Kamil Kuca, Zdenek Hodny, Eugenie Nepovimova","doi":"10.1186/s12935-026-04308-0","DOIUrl":"https://doi.org/10.1186/s12935-026-04308-0","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence is a stress-induced state characterized by irreversible cell cycle arrest. Senescent cells accumulate during aging and contribute to age-related diseases, including neurodegeneration, cancer, and type 2 diabetes mellitus. The mTOR signaling pathway plays a critical role in maintaining and regulating senescence-associated features.</p><p><strong>Methods: </strong>We employed virtual high-throughput screening and fragment-based design to identify novel small-molecule competitive mTOR kinase inhibitors with favorable physicochemical properties. Six lead compounds (1-6) were selected, and torkinib (7) was synthesized and used as a reference.</p><p><strong>Results: </strong>Biochemical and cell-based assays revealed that torkinib and compounds 5 and 6 inhibited mTORC1-mediated phosphorylation of p70 S6K. Compound 5 exhibited cytostatic effects in both non-transformed human cells and glioma cancer cells, with greater sensitivity observed in the latter. Unlike the rapalog temsirolimus, both torkinib and compound 5 suppressed migration in multiple glioblastoma cell lines. Notably, compound 5 induced a transient autophagy flux distinct from that elicited by other tested mTOR inhibitors. Furthermore, compound 5 reduced radiation-induced expression of senescence-associated secretory phenotype (SASP) markers, including IL-1α, IL-6, and IL-8. Additional senomorphic effects included decreased cell size and reduced senescence-associated β-galactosidase activity. In vivo, compound 5 showed slightly higher toxicity than torkinib, likely due to improved solubility.</p><p><strong>Conclusions: </strong>Compound 5 demonstrates distinct biological effects compared to torkinib and represents a promising candidate for further development as an mTOR inhibitor targeting both cancer and senescent cells.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa-miR-149-5p targets Men1 to inhibit the progression of gastric cancer through the HSPA6/JNK pathway.","authors":"Jin-Xun Jiang, Shi-Jie Zhang, Kun Zhao, Kai-Tian Zheng, Shan-Hu Wang, Tian-de Chen, Zhen Wang","doi":"10.1186/s12935-026-04314-2","DOIUrl":"https://doi.org/10.1186/s12935-026-04314-2","url":null,"abstract":"<p><strong>Background: </strong>The mechanisms underlying gastric cancer (GC) progression, including recurrence and metastasis, remain unclear. Studies have reported that microRNAs and Men1 are closely associated with multiple tumors, including GC. Therefore, assessing the impact of Men1 on GC and investigating the underlying mechanisms are essential.</p><p><strong>Methods: </strong>This study assessed Men1 expression using GEPIA2 data and GC patient samples; examined the association between Men1 and clinicopathological features and prognosis; investigated the role of Men1 in GC progression by modulating its expression in vitro; explored potential mechanisms using RNA sequencing, dual-luciferase reporter assays, RT-qPCR, and western blotting; and evaluated the impact of Men1 on GC metastasis using a nude mouse lung metastasis model with in vivo imaging. We also identified microRNAs targeting Men1 and assessed their impact on GC using in vitro and in vivo experiments.</p><p><strong>Results: </strong>The results indicate that Men1 is significantly overexpressed in GC and is associated with aggressive clinicopathological features and poor prognosis. Men1 enhanced GC cell proliferation and migration in vitro and prompted lung metastasis in vivo. Modulating Men1 expression in GC cells altered the levels of HSPA6, p-JNK, p-JUND, and EMT-related molecules, including N-cadherin, vimentin, MMP2, MMP9, and Snail. Hsa-miR-149-5p is identified as a microRNA that targets Men1 and inhibited GC progression in vitro and in vivo.</p><p><strong>Conclusion: </strong>Hsa-miR-149-5p targeted Men1 to inhibit the progression of GC, possibly by regulating the HSPA6/JNK/JUND axis and modulating EMT. Further studies are needed to confirm these findings.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotic-derived EPS-ZnO nanoparticles: therapeutic potential in colorectal cancer gene regulation.","authors":"Saeideh Afsharipoor, Razieh Nazari, Anoosh Eghdami, Mahdi Fasihi-Ramandi, Mohammad Reza Zolfaghari","doi":"10.1186/s12935-026-04247-w","DOIUrl":"https://doi.org/10.1186/s12935-026-04247-w","url":null,"abstract":"<p><p>Colorectal cancer (CRC), the third most common and second deadliest cancer worldwide, arises from the abnormal growth of epithelial cells in the colon or rectum. This study focused on the oncogenes BCL9, KRAS, and WNT10A, alongside the tumor suppressor genes PDCD4, PTEN, and LRIG3, in the SW480 cell line. Probiotics, valued for their antioxidant and anti-cancer effects-especially due to their exopolysaccharides (EPS)-are promising in cancer prevention. Nanoparticles (NPs) hold great potential for diagnosing and treating various diseases, including cancer. Among them, zinc oxide NPs (ZnONPs) stand out for their unique physical and chemical properties, making them widely used in drug delivery, cancer diagnosis, and therapy. In this study, EPS were extracted and purified from the probiotic bacterium Lactiplantibacillus plantarum at a concentration of 301 ± 0.12 mg/L, and subsequently employed in the biosynthesis of ZnONPs, achieving an optimal yield of approximately 61.2%. Validation tests (UV-Vis, XRD, FTIR, FE-SEM, TEM, and zeta potential analysis) were conducted on the ZnONPs coated with exopolysaccharide (EPS-ZnONPs). The cytotoxicity of EPS and EPS-ZnONPs was assessed on the SW480 cell line, and their antioxidant properties were evaluated. Quantitative cycle variations (∆∆Cqs) measured via the Real-time PCR system, following the treatment of the cancerous cell line with the target metabolites, demonstrated reduced expression of oncogenes and increased expression of tumor suppressors. The results indicated that EPS extracted from probiotics, as well as EPS-ZnONPs, could serve as effective agents in the treatment of CRC by modulating the expression levels of genes involved in the development of this cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of a risk scoring model based on machine learning and validation of the role of the key gene SERPINE1 in the progression of colon cancer.","authors":"Xin Li, Nana Li, Yujie Wang, Qixiang Han, Xiaodong Li, Qiushi Tu, Boshi Sun, Hao Yang, Yuan Gao","doi":"10.1186/s12935-026-04322-2","DOIUrl":"https://doi.org/10.1186/s12935-026-04322-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Colon cancer (CC) is a highly prevalent malignant tumor with a high mortality rate worldwide. Despite recent advancements in diagnosis and treatment, the overall prognosis for patients remains poor, especially for those with metastasis. Exploring key genes associated with the prognosis of patients with colon cancer, establishing effective molecular models, and validating their functions are necessary to optimize patient management and develop novel therapeutic strategies. This study aimed to reveal the role of the key gene SERPINE1 in the progression of colon cancer and its potential clinical application value through bioinformatics analysis and experimental validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Multimodal data from colon cancer patients were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) with a fold change ≥ 2 and an adjusted P value less than 0.05 were screened. A protein‒protein interaction network was constructed using the STRING database, and 40 core genes were identified using Cytoscape software. Genes closely related to the prognosis of colon cancer patients were further selected using LASSO regression and Cox proportional hazards regression models to construct a risk scoring model for assessing patients' survival risk. The model performance was evaluated in combination with immune cell infiltration analysis and ROC curve assessment, and the associations between the target genes and the tumor immune microenvironment were explored. The expression and function of SERPINE1 were subsequently investigated. The expression level of SERPINE1 in colon cancer tissues was analyzed by Western blotting. The effects of SERPINE1 knockdown on the migration and invasion abilities of colon cancer cells were assessed by scratch wound healing and Transwell assays. The impact of SERPINE1 knockdown on tumor formation and metastasis in colon cancer cells was verified through mouse tumor and metastasis models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The bioinformatics analysis identified seven target genes related to the prognosis of colon cancer, namely, CAMK2B, KIF1A, OPCML, SCN5A, SERPINE1, TH, and UCHL1, based on which a risk scoring model was constructed. Further analysis revealed that the risk score was not only associated with patients' survival prognosis but also significantly correlated with the infiltration of immune cells such as T cells and macrophages in the tumor immune microenvironment. Among these seven genes, SERPINE1 was highly expressed in colon cancer and was significantly positively correlated with a poor prognosis. In vitro experiments revealed that SERPINE1 knockdown inhibited the proliferation, migration, and invasion of colon cancer cells. Western blot experiments indicated that SERPINE1 knockdown upregulated the expression of epithelial cadherin (E-cadherin, E-CAD) and downregulated the expression of neural cadherin (N-cadherin, N-CAD) and vimentin ","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized immunotherapy in HCC: synthesis, delivery, and clinical progress of mRNA-based vaccines.","authors":"Shirin Tavakoli, Ali Hassanzadeh, Maryam Samareh Salavatipour, Leila Hojjati, Somayeh Shamlou, Amin Kamrani, Nasim Vousooghi, Maryam Iranpour","doi":"10.1186/s12935-026-04265-8","DOIUrl":"https://doi.org/10.1186/s12935-026-04265-8","url":null,"abstract":"<p><p>Messenger RNA (mRNA)-based vaccines have quickly developed as a unique approach to cancer immunotherapy with specific antigen expression, flexible design, and safety. They are broadly categorized into self-amplifying mRNA (SAM) vaccines and non-replicating mRNA vaccines. SAM vaccines contain viral replicase elements enabling intracellular RNA amplification and strong antigen expression, whereas non-replicating mRNA vaccines encode only the target antigen and rely on direct translation for immunogenicity. Hepatocellular carcinoma (HCC) is a highly aggressive cancer that often exhibits resistance to standard-of-care therapy and appears to benefit from being targeted with mRNA vaccines to produce an anti-tumor immune response. Herein, we review the stepwise approach of vaccine construction of mRNA vaccines, including building a DNA template, in vitro transcription, capping, polyadenylation, and purification of the mRNA, and their delivery as lipid nanoparticles (LNPs), dendritic cells, or naked RNA. In addition, we present a synthesis of progress made through the identification of HCC-specific neoantigens and high-affinity neoantigens (HANs) that activate cytotoxic T cells, correlating with better patient outcomes. Recent preclinical and clinical studies demonstrate the safety and efficacy of mRNA vaccines that encode either tumor-associated or patient-specific neoantigens, often in combination with local therapeutics or immune checkpoint inhibitors. We offer further considerations regarding combinations of mRNA vaccines with strategies including but not limited to adoptive cell therapy, tumor suppressor gene restoration, anti-angiogenesis drugs, and metabolic reprogramming. In many ways, a key consideration is the strategies being developed to overcome the immunosuppressive tumor microenvironment in the liver, and mRNA-induced co-stimulation (e.g., OX40L), TP53 gene editing, and targeting of myeloid-derived suppressor cells. Overall, our review has offered perspectives on the many types of opportunistic strategies being investigated, combining mRNA vaccines to not only prime for anti-tumor immunity or alternate human sources of anti-tumor immunity but also remodel the immunologic landscape that permeates HCC. With numerous ongoing studies and rapid technology advances, mRNA-based immunotherapies are sure to transform how we manage liver cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting caveolin-1: dual challenges in tumor immunity and drug therapy strategies.","authors":"Xiyue Ge, Tianyi Song, Xiangyan Guo, Jiajie Li, Zenghua Wang, Yaning Shi, Li Qin, Chanjuan Zhang","doi":"10.1186/s12935-026-04324-0","DOIUrl":"https://doi.org/10.1186/s12935-026-04324-0","url":null,"abstract":"<p><p>Tumor immunity is a crucial defense mechanism that suppresses tumor initiation and delays tumor progression. The interplay between tumor metabolic reprogramming and immune evasion is a putative determinant in the tumor progression. Caveolin-1 (Cav-1) is a major biomarker of caveolae and is involved in cell signaling, lipid metabolic reprogramming, and antitumor immune responses. Cav-1 is widely expressed in immune cells and tumor cells, with frequent upregulation in breast cancer, liver cancer, lung cancer, pancreatic cancer, glioma, and melanoma. However, Cav-1 expression is context-dependent and varies across cancer subtypes, including gastric cancer. This review discusses the structure and functions of Cav-1, emphasizing its role in tumor-associated immune cells. We summarized Cav-1-mediated lipid metabolic reprogramming regulates antitumor immunity and highlighted challenges in developing Cav-1-targeting drugs. Notably, tumor cell metabolic reprogramming not only supports cancer cell progression but also drives immunosuppression via inhibitory cytokines like transforming growth factor-β (TGF-β) and interleukin-4 (IL-4), fostering immune evasion and therapy resistance. While Cav-1 represents a potential biomarker and therapeutic target, its heterogeneous expression and context-specific functions necessitate further research to develop precise therapies. Future investigations into the mechanisms of Cav-1 in tumor immunity may pave the way for more effective cancer treatments.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}