Frontiers in Oncology最新文献

{"title":"Clinical value of cystatin S in patients with colorectal cancer chemotherapy.","authors":"Tingting Han, Shijie Deng, Dongmei Xia, Kun Jin, Chao Mei","doi":"10.3389/fonc.2025.1640646","DOIUrl":"https://doi.org/10.3389/fonc.2025.1640646","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the diagnostic utility of serum cystatin S (CST4) in chemotherapy-treated colorectal cancer (CRC) patients and establish its complementary value to conventional tumor markers.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed 81 CRC patients receiving chemotherapy and 83 colorectal polyp controls. Serum CST4 levels were quantified by ELISA alongside six conventional tumor markers (CEA, CA125, CA153, CA199, AFP, CA724). Diagnostic performance was assessed through ROC analysis and multivariate logistic regression. Additionally, <i>in vitro</i> experiments with HCT116 CRC cells were conducted to validate the regulatory relationship between CST4 and PDGFRB.</p><p><strong>Results: </strong>CRC patients exhibited significantly elevated CST4 levels compared to polyp controls (median [IQR]: 54.07 [32.18-91.49] vs 37.48 [24.18-49.28] U/mL, P<0.05). CST4 demonstrated superior diagnostic performance with AUC = 0.689 (95%CI:0.607-0.771), outperforming individual conventional markers. Notably, CST4 maintained diagnostic independence across tumor stages (P>0.05) and age groups. A multimodal diagnostic model combining CST4 with CEA, CA724, and CA125 significantly enhanced detection capability (AUC = 0.828, sensitivity 74.1%, specificity 81.9%), representing a 28.4% sensitivity improvement over CST4 alone. <i>In vitro</i>, CST4 knockdown in HCT116 cells led to a 68.3% reduction in PDGFRB expression (P<0.0001), validating a regulatory axis between CST4 and PDGFRB.</p><p><strong>Conclusion: </strong>CST4 emerges as a stable post-chemotherapy biomarker that effectively discriminates malignant colorectal lesions. Its integration with conventional markers creates a robust diagnostic algorithm, while functional validation supports a mechanistic role via PDGFRB-mediated pathways. These findings position CST4 as a promising candidate for therapeutic monitoring and recurrence detection in CRC management.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1640646"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HOXB7 drives bladder cancer progression via H-Ras/ERK signaling: a potential therapeutic target and prognostic biomarker.","authors":"Xulong Chen, Kehua Jiang, Kun Chen, Yu An, Qing Wang, Xiaolong Chen, Peng Zhang, Quliang Zhong, Fa Sun","doi":"10.3389/fonc.2025.1645803","DOIUrl":"https://doi.org/10.3389/fonc.2025.1645803","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BC) is a common malignancy characterized by high recurrence and poor prognosis. HOXB7, a member of the HOX gene family, is aberrantly expressed in various tumors, but its role in BC remains unclear.</p><p><strong>Methods: </strong>HOXB7 expression in BC was analyzed using public databases (GEPIA, UALCAN) and validated by immunohistochemistry on a tissue microarray of 36 BC patients. <i>In vitro</i> experiments using BC cell lines (5637 and T24) were conducted to investigate the effects of HOXB7 knockdown or overexpression on cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT). Western blotting and rescue assays with ERK pathway modulators (Ro67-7476 and PD98059) were performed to assess the involvement of the H-Ras/Raf-1/MEK/ERK signaling cascade. Xenograft mouse models were employed to evaluate tumorigenicity <i>in vivo</i>.</p><p><strong>Results: </strong>HOXB7 was significantly upregulated in BC tissues and cell lines, correlating with advanced tumor stage and poor overall survival. HOXB7 silencing inhibited BC cell proliferation, migration, invasion, and EMT, while promoting apoptosis. Conversely, HOXB7 overexpression produced the opposite effects. Mechanistically, HOXB7 activated the H-Ras/Raf-1/MEK/ERK pathway, as indicated by increased phosphorylation of MEK and ERK. These effects were reversed by pharmacological inhibition or activation of ERK signaling. <i>In vivo</i>, HOXB7 knockdown suppressed tumor growth and ERK pathway activation.</p><p><strong>Conclusion: </strong>This study provides the first comprehensive experimental evidence that HOXB7 drives BC progression via activation of the H-Ras/Raf-1/MEK/ERK pathway. These findings highlight HOXB7 as a potential prognostic biomarker and therapeutic target in BC. Furthermore, our results lay the foundation for future investigations into the broader molecular and immunological networks modulated by HOXB7 in BC.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1645803"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A methodology for optimizing treatment head angle arrangement for multi-angle FLASH intensity modulated radiation therapy platforms.","authors":"Weijie Cui, Chenlei Guo, Zhihui Hu, Yunxiang Wang, Kuo Men, Jianrong Dai","doi":"10.3389/fonc.2025.1628281","DOIUrl":"https://doi.org/10.3389/fonc.2025.1628281","url":null,"abstract":"<p><strong>Purpose: </strong>Flash therapy technology has been introduced, and several systems have been developed for its implementation. One such FLASH radiotherapy platform employs multiple treatment heads that deliver radiation to a target simultaneously. However, the optimal number of treatment heads and their precise angular configuration needed to best meet clinical requirements remain to be determined.</p><p><strong>Methods and materials: </strong>In this study, each treatment head angle is treated as an independent variable, and the total angular discrepancy between a set of beam directions from clinically used plans and those generated by a virtual FLASH radiotherapy platform is defined as the objective function. This problem is solved using an optimization technique known as Adaptive Simulated Annealing (ASA). The performance of the proposed optimization model was evaluated using a dataset of 69,928 beams from 8,866 intensity-modulated radiation therapy (IMRT) plans collected over a two-year period in our department. These plans represent various types of common tumors, including nasopharyngeal, breast, esophageal, lung, and rectal cancers. The total angular discrepancy was compared between the beam directions obtained through the optimized treatment head arrangement and the directions used in clinical practice.</p><p><strong>Results: </strong>For a virtual FLASH therapy platform equipped with five treatment heads, we obtained the optimized treatment head angle arrangements both with and without the constraint of an imaging system. Under the imaging system constraint, the optimized angles were 0°, 40.4°, 169.4°, 201.2°, and 239.8°, resulting in an average discrepancy of 38.9°compared to the beam directions used in the reference treatment plan cohort. Without the imaging system constraint, the optimized angles were 0°, 155.4°, 234.4°, 266.2°, and 304.8°, yielding an average discrepancy of 37.8°. In contrast, equally spaced treatment head angles produced an average discrepancy of 78.4°.</p><p><strong>Conclusion: </strong>A methodology for optimizing the treatment head angle arrangement for multi-angle FLASH radiotherapy platforms is proposed. The optimized configuration provides an effective solution for clinical applications, balancing performance with practical feasibility.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1628281"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role and prognostic value of oncostatin M and its receptor OSMR in acute myeloid leukemia, myeloproliferative neoplasms and non-hematological malignancies.","authors":"Jean-Pierre Lévesque, Kavita Bisht, Kylie A Alexander, Ingrid G Winkler","doi":"10.3389/fonc.2025.1636570","DOIUrl":"https://doi.org/10.3389/fonc.2025.1636570","url":null,"abstract":"<p><p>The oncostatin M receptor (OSMR) has recently emerged as an adverse prognostic factor in acute myeloid leukemia (AML) and several non-hematological malignancies. In this perspective, we discuss how oncostatin M (OSM) and its receptor OSMR regulate tumor cells as well as mesenchymal and endothelial cells, which are key components of hematopoietic stem cell and tumor stem cell niches, and how these mechanisms could explain the poor prognosis associated with high expression of OSM and OSMR in hematological and non-hematological malignancies.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1636570"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence factor and mechanism of FLASH effect.","authors":"Tingyu Feng, Tianyang He, Wentao Ye, Lisha Xiang","doi":"10.3389/fonc.2025.1669228","DOIUrl":"https://doi.org/10.3389/fonc.2025.1669228","url":null,"abstract":"<p><p>FLASH radiotherapy (FLASH-RT) represents an innovative treatment modality utilizing ultra-high dose-rate irradiation (>40 Gy/s). The FLASH effect, induced by FLASH-RT, is characterized by the selective radioprotective effect of normal tissue while preserving tumor control efficacy. Currently, FLASH effect has been confirmed in many preclinical studies and clinical studies. However, the mechanism and the influencing factors of FLASH effect remain ambiguous. This review systematically summarizes current understanding of the mechanism and influencing factors of FLASH effect, providing theoretical basis for the future study and application of FLASH-RT.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1669228"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning assisted breathomic approach for early-stage thoracic cancer detection.","authors":"Zhenguang Chen, Minhua Peng, Pengnan Fan, Sai Chen, Xinxin Cheng, Bo Xu, Ruiping Chen, Xiao Hu, Wei Wei, Tingting Zhao, Jun Kong, Weiliang Liang, Xiangcheng Qiu, Sitong Chen, Junqi Wang","doi":"10.3389/fonc.2025.1635280","DOIUrl":"https://doi.org/10.3389/fonc.2025.1635280","url":null,"abstract":"<p><strong>Objective: </strong>This study explores the feasibility of using breathomic biomarkers analyzed by machine learning as a non-invasive diagnostic tool to differentiate between benign and malignant thoracic lesions, aiming to enhance early detection of thoracic cancers and inform clinical decision-making.</p><p><strong>Methods: </strong>This study enrolled 132 participants with confirmed diagnosis of lung cancer, esophageal cancer, thymoma, and benign diseases. Exhaled breath samples were analyzed by thermal desorption-gas chromatography-mass spectrometry. A logistic regression algorithm was employed to construct a classification model for benign and malignant thoracic lesions. This model was trained on a subset of 80 cases and subsequently validated in a separate set comprising 52 samples.</p><p><strong>Results: </strong>A logistic regression model based on thirteen exhaled volatile organic compounds (VOCs) was developed to differentiate benign and malignant thoracic lesions. The 13-VOC model achieved an AUC of 0.85 (0.72, 0.96), accuracy of 0.79 (0.66, 0.88), sensitivity of 0.82 (0.67, 0.91), and a specificity of 0.71 (0.45, 0.88). It correctly classified 80% of lung cancer, 80% of thymoma, and 100% of esophageal cancer cases, distinguishing 71.4% of benign lesions. For lung cancer, the model achieved an AUC of 0.79 (0.57, 0.98), sensitivity of 0.80 (0.63, 0.91), and specificity of 0.63 (0.31, 0.86), with 81.8% accuracy in detecting early-stage (Stage 0 + I + II) disease. The model outperformed a 4-serum tumor marker panel in sensitivity (0.90 vs. 0.39, <i>p</i> < 0.001). Additionally, in a cohort of 58 cancer patients, model-predicted risk significantly decreased post-surgery (<i>p</i> < 0.01), indicating a strong correlation with disease burden reduction.</p><p><strong>Conclusion: </strong>This study demonstrates the feasibility of utilizing breathomics biomarkers for developing a non-invasive machine learning model for the early diagnosis of thoracic malignancies. These findings provide a foundation for breath analysis as a promising tool for early cancer detection, potentially facilitating improved clinical decision-making and enhancing patient outcomes.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1635280"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathological grading affects survival in patients with isocitrate dehydrogenase-wildtype gliomas.","authors":"Ziming Hou, Dongyuan Liu, Zhe Hou, Hongbing Zhang, Hao Wang","doi":"10.3389/fonc.2025.1570941","DOIUrl":"10.3389/fonc.2025.1570941","url":null,"abstract":"<p><strong>Background: </strong>The World Health Organization (WHO) Classification of Tumors of the Central Nervous System (2021) defines lower-grade (WHO grade II/III) isocitrate dehydrogenase (IDH) wild-type astrocytoma as glioblastoma, IDH-wildtype, WHO grade 4. However, this definition is conditional. Notably, the traditional histopathological grade is no longer used, and the independent prognostic factor of tumor grade in IDH wild-type gliomas remains unclear. In this study, we aimed to determine if histopathological grade is an independent prognostic factor.</p><p><strong>Methods: </strong>The clinical data and pathological information of 647 patients with IDH wild-type gliomas from the Chinese Glioma Genome Atlas (CGGA) database (2006-2019) were retrospectively analyzed. All patients were stratified according to histopathological grade and its prognostic significance in IDH wild-type gliomas. Univariate and Cox's multivariate analyses were used to determine the prognostic significance.</p><p><strong>Results: </strong>The median follow-up time was 100.4 months, and the median survival time was 20.3 months. The histopathological grade was an important independent prognostic factor in the univariate and multivariate analyses, and a higher grade was associated with poor overall survival and progression-free survival. After further stratification by the extent of resection and postoperative adjuvant treatment, the histopathological grade remained a significant prognostic factor.</p><p><strong>Conclusions: </strong>In this study, histopathological grade affected survival in IDH-wild-type gliomas. This effect appears to be independent of the extent of resection and postoperative treatment. Thus, we suggest that clinical treatment of patients with IDH wild-type gliomas should continue to consider histopathological grade along with the molecular characteristics of the tumors.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1570941"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of amino acid metabolism-related gene Leucyl-tRNA synthetase 1 (LARS1) as a potential prognostic and therapeutic target in hepatocellular carcinoma.","authors":"Qiyu Shi, Yirong Chi, Ziyi Peng, Chao Li, Jingwen Zhao, Jie Zhang","doi":"10.3389/fonc.2025.1675018","DOIUrl":"10.3389/fonc.2025.1675018","url":null,"abstract":"<p><strong>Introduction: </strong>Amino acid metabolism plays a critical role in tumorigenesis in hepatocellular carcinoma (HCC). Thus, we explore the amino acid metabolic profile in HCC to construct effective prognosis model and identify novel potential therapeutic target for HCC.</p><p><strong>Methods: </strong>The transcriptomic data and clinical information of HCC patients were directly obtained from The Cancer Genome Atlas (TCGA). Then we classified them into two subtypes based on selected amino acid metabolism-related genes (SARGs) and explored the differences between them. Besides, risk models were constructed based on SARGs through LASSO regression, and we further validated and evaluated the predictive effect of the model. Subsequently, we validated the key gene of LARS1 in the model. We analyzed the discrepancy of LARS1 in tumor and adjacent non-tumor tissues in both TCGA and the Gene Expression Omnibus (GEO) database and the results were verified in HCC patients undergoing hepatectomy from our hospital via PCR and Immunohistochemistry (IHC). Finally, we explored the biological function of LARS1 <i>in vitro</i>.</p><p><strong>Results: </strong>We classified HCC patients into Cluster A and B subtypes based on 81 SARGs. And patients in Cluster B exhibited significantly poorer prognosis, higher tumor malignancy levels, higher TIDE scores and T cell exhaustion or dysfunction. Then 15 genes were included to construct the risk model. The risk score was positively associated with poor prognosis. We further extracted LARS1 as the key gene of the model and found that high LARS1 tended to have poorer prognosis with higher expression in tumor tissues than in adjacent non-tumor ones in both TCGA and GEO. PCR and IHC were conducted for verification. Suppression of LARS1 markedly inhibited the growth of HCC cells. Additionally, LARS1 knockdown significantly impeded cellular migration and invasion <i>in vitro</i>, with increased autophagy flux.</p><p><strong>Conclusion: </strong>We have successfully developed a prognostic model based on 15 genes associated with amino acid metabolism. We also verified that knockdown of LARS1 significantly inhibited the proliferation, invasion and migration of HCC <i>in vitro</i>, with increased autophagy flux, indicating that LARS1 could be a potential therapeutic target for HCC.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1675018"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IQGAP1: cross-disease target via receptor-pathway networks.","authors":"Shaopeng Zhu, Yunpeng Zou, Jie Guo, Wenqi Ma, Laitong Lu, Ronghan Liu, Jianning Kang, Kai Zhao, Jiangbo Zhong","doi":"10.3389/fonc.2025.1632060","DOIUrl":"10.3389/fonc.2025.1632060","url":null,"abstract":"<p><p>IQGAP1, a versatile scaffolding protein, critically regulates cytoskeletal organization, cell motility, proliferation, and signaling cascades. Beyond coordinating these cellular functions, it is increasingly recognized as a key driver in malignancies, immune dysfunction, metabolic dysregulation, and cardiovascular pathologies. By binding receptor tyrosine kinases, small GTPases, and downstream effectors, IQGAP1 modulates oncogenesis, immune evasion, and metabolic imbalance, while contributing to chemoresistance. This review synthesizes advances in IQGAP1's structural domains, disease-specific signaling networks, and therapeutic targeting strategies, emphasizing its translational potential in developing precision therapies for cancer, metabolic syndromes, and immune disorders.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1632060"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The paradoxical role of stem cells in osteosarcoma: from pathogenesis to therapeutic breakthroughs.","authors":"Zhengbing Su, Xiang Fang, Hong Duan","doi":"10.3389/fonc.2025.1643491","DOIUrl":"10.3389/fonc.2025.1643491","url":null,"abstract":"<p><p>Osteosarcoma (OS), the most prevalent primary malignant bone tumor in adolescents, exhibits a high metastatic potential and resistance to therapy. This characteristic results in a dismal prognosis in advanced cases even following multimodal therapies. This review synthesizes the dual roles of stem cells in OS pathogenesis and therapeutic innovation. Cancer stem cells (CSCs) drive tumor initiation, progression, and chemoresistance through dysregulated molecular pathways that include Wnt/β-catenin, Notch, and Hedgehog signaling, with key markers such as CD133 and CXCR4 contributing to stemness maintenance and metastasis. Concurrently, mesenchymal stem cells (MSCs) paradoxically influence OS progression. Although their tumor-homing capacity enables targeted drug delivery (e.g., IDD-1040-paclitaxel complexes) and immunomodulation, MSC-derived factors like TGF-β can promote cancer-associated fibroblast differentiation and immune evasion. The immunosuppressive tumor microenvironment (TME), characterized by hypoxia-induced HIF-1α activation, metabolic reprogramming, and M2 macrophage polarization, further facilitates CSC resilience and therapy resistance. Emerging strategies-including CSCs-targeted agents (AZD1080, DNMTi/HDACi), CRISPR/Cas9-engineered CD133-directed CAR-T cells, and MSC-mediated delivery of oncolytic viruses-show preclinical promise in overcoming these barriers. However, critical challenges persist: intratumoral CSC heterogeneity limits targeted therapy efficacy; MSC functional plasticity risks tumor promotion via fusion or batch variations; and inefficient cell homing due to pulmonary entrapment reduces therapeutic delivery. Future directions necessitate biomarker-guided combinatorial approaches, optimized MSC administration routes (e.g., intra-arterial injection), and integrated multi-omics profiling to address translational bottlenecks. Resolving these issues will advance personalized stem cell-focused therapies for OS.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1643491"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}