Frontiers in Oncology最新文献

{"title":"Integrating multimodal ultrasound imaging and machine learning for predicting luminal and non-luminal breast cancer subtypes.","authors":"Yan Fu, Huang Jing Chen, Hao Zhang, Dong Jie Liu, Xi Chen, Cheng Yu Qiu, Wen Wu Lu, Hao Miao Bai, Qiu Wei Li, Guo Xue Li, Zi Jun Shen, Chang Jiang Gu, Yuan Peng Zhang, Xue Jun Ni","doi":"10.3389/fonc.2025.1558880","DOIUrl":"https://doi.org/10.3389/fonc.2025.1558880","url":null,"abstract":"<p><strong>Rationale and objectives: </strong>Breast cancer molecular subtypes significantly influence treatment outcomes and prognoses, necessitating precise differentiation to tailor individualized therapies. This study leverages multimodal ultrasound imaging combined with machine learning to preoperatively classify luminal and non-luminal subtypes, aiming to enhance diagnostic accuracy and clinical decision-making.</p><p><strong>Methods: </strong>This retrospective study included 247 patients with breast cancer, with 192 meeting the inclusion criteria. Patients were randomly divided into a training set (134 cases) and a validation set (58 cases) in a 7:3 ratio. Image segmentation was conducted using 3D Slicer software, adhering to IBSI-standardized radiomics feature extraction. We constructed four model configurations-monomodal, dual-modal, trimodal, and four-modal-through optimized feature selection. These included monomodal datasets comprising 2D ultrasound (US) images, dual-modal datasets integrating 2D US with color Doppler flow imaging (CDFI) (US+CDFI), trimodal datasets incorporating strain elastography (SE) alongside 2D US and CDFI (US+CDFI+SE), and four-modal datasets combining all modalities, including ABVS coronal imaging (US+CDFI+SE+ABVS). Machine learning classifiers such as logistic regression (LR), support vector machines (SVM), AdaBoost (adaptive boosting), random forests(RF), linear discriminant analysis(LDA), and ridge regression were utilized.</p><p><strong>Results: </strong>The four-modal model achieved the highest performance (AUC: 0.947, 95% CI: 0.884-0.986), significantly outperforming the monomodal model (AUC 0.758, ΔAUC +0.189). Multimodal integration progressively enhanced performance: trimodal models surpassed dual-modal and monomodal approaches (AUC 0.865 vs 0.741 and 0.758), and the four-modal framework showed marked improvements in sensitivity (88.4% vs 71.1% for monomodal), specificity (92.7% vs 70.1%), and F1 scores (0.905).</p><p><strong>Conclusion: </strong>This study establishes a multimodal machine learning model integrating advanced ultrasound imaging techniques to preoperatively distinguish luminal from non-luminal breast cancers. The model demonstrates significant potential to improve diagnostic accuracy and generalization, representing a notable advancement in non-invasive breast cancer diagnostics.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1558880"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12541423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354284","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":"Case report: Anlotinib plus oral etoposide: a potential salvage therapy based on insights from EGFR-TKI-resistant SCLC transformation PDX and clinical settings.","authors":"Zixi Wang, Xiaoyu Li, Lili Jiang, Weiya Wang, Kai Xiao, Ting Zhang, Li Li, Dan Li, Yongsheng Wang","doi":"10.3389/fonc.2025.1661273","DOIUrl":"https://doi.org/10.3389/fonc.2025.1661273","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) transformation is one of the resistance mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in patients with lung adenocarcinoma (LUAD). Platinum-etoposide chemotherapy is the most common regimen for patients with SCLC transformation. Despite a high initial response rate, patients experience rapid disease progression, and there is a paucity of evidence for further-line therapy. In this study, we report two cases of patients with EGFR 19del-mutated and EGFR-TKI-resistant transformed SCLC who failed with platinum-etoposide chemotherapy. We explored a novel combination strategy of anlotinib and orally administered etoposide in these two patients, guided by the results of a patient-derived tumor xenograft (PDX) model. The combination regimen was clinically applied when platinum-etoposide chemotherapy failed, and both patients benefited from the treatment. To our knowledge, this is the first report of anlotinib plus oral etoposide as a potential salvage therapy for patients with EGFR-TKI-induced SCLC transformation resistant to platinum-based chemotherapy. Both the PDX model and clinical cases support the efficacy of this regimen, providing a promising therapeutic option for patients with SCLC transformation after platinum-etoposide chemotherapy resistance.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1661273"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353856","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":"Clinical practice of early screening and risk-stratified management for oral potentially malignant disorders.","authors":"Beibei Ge, Xinqiang Zhu, Meimei Ma, Yingxin Ju, Yannan Ma, Yong Song","doi":"10.3389/fonc.2025.1697676","DOIUrl":"https://doi.org/10.3389/fonc.2025.1697676","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the application value of standardized screening and risk-stratified management in the clinical practice of Oral Potentially Malignant Disorders (OPMDs) for improving early diagnosis rates and optimizing intervention strategies.</p><p><strong>Methods: </strong>A total of 312 OPMD patients diagnosed between January 2017 and December 2022 were enrolled. A screening pathway of \"initial screening (questionnaire + visual/tactile examination) - refined screening (pathological biopsy)\" was established. Risk stratification (low, intermediate, high) was performed using a modified Proliferative Verrucous Leukoplakia (PVL)-based scoring system. Multidisciplinary team (MDT) management was implemented. Risk factors for malignant transformation were analyzed using Cox regression.</p><p><strong>Results: </strong>The high-risk group had a significantly higher malignant transformation rate than the intermediate and low-risk groups (12.5% vs. 3.5% vs. 0%, P<0.001), with a shorter median time to transformation (23.4 months). Severe epithelial dysplasia (HR = 6.24), lesions located in the tongue ventral/floor of mouth (HR = 3.34), and betel quid chewing history (HR = 2.62) were identified as independent risk factors. The MDT model achieved a 2-year cancer-free survival rate of 91.4% in high-risk patients and improved follow-up compliance to 83.3%.</p><p><strong>Conclusion: </strong>An OPMD management model based on risk stratification and MDT collaboration can effectively identify high-risk patients, optimize intervention timing, and improve prognosis. This model is suitable for promotion in primary care hospitals.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1697676"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354257","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":"Whole-exome sequencing in Saudi colorectal cancer patients reveals distinct mutational patterns and population specific pathogenic variants.","authors":"Hanan E Alatwi, Amnah A Alharbi, Rashid Mir, Othman R Alzahrani, Abdulrahman H Alessa, Yousef M Hawsawi, Mohammed Ali Arishi, Aziz Dhaher Albalawi","doi":"10.3389/fonc.2025.1679528","DOIUrl":"https://doi.org/10.3389/fonc.2025.1679528","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) shows significant inter-population heterogeneity in its genomic landscape, yet Middle Eastern populations are underrepresented in large-scale sequencing studies. This exploratory study aims to characterize somatic mutations and disrupted signaling pathways in Saudi Arabian CRC patients.</p><p><strong>Methods: </strong>We performed whole-exome sequencing (WES) on tumor DNA from 24 Saudi CRC patients. Somatic variants were identified and analyzed in a curated panel of cancer-related genes. Comparative analysis was conducted against The Cancer Genome Atlas colorectal cancer dataset (TCGA-COADREAD), and pathway enrichment analysis was performed.</p><p><strong>Results: </strong>Somatic variants were identified in 23 tumors, with recurrent mutations in <i>BRCA2</i> (61%), <i>TCF7L2</i> (52%), <i>EGFR</i> (43%), and <i>SOS1</i> (43%). Compared to TCGA-COADREAD, mutation frequencies were significantly higher in <i>BRCA2</i>, <i>EGFR</i>, <i>SLC25A5</i>, and <i>PIK3R2</i> (adjusted p < 0.0001). Among 258 total variants, 43% were novel, and 25 were classified as pathogenic, likely pathogenic, or deleterious, including 13 novel variants across nine genes. Pathway analysis revealed frequent disruptions in WNT/β-catenin (65%), homologous recombination (61%), PI3K (48%), and RTK/RAS (43%) signaling pathways.</p><p><strong>Conclusion: </strong>Our results reveal a distinct mutational profile in Saudi CRC patients, characterized by novel and enriched somatic variants affecting key oncogenic pathways. These findings underscore the necessity of including underrepresented populations in cancer genomics to support globally equitable precision oncology.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1679528"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354340","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 effect of tislelizumab on complete and pathological complete response in non-small cell lung cancer: a systematic review and meta-analysis.","authors":"Qian Feng, Xiaoxia Yan, Liping Gao, Hui Li, Baik Sarah, Russo Anna, Hongying Jiang","doi":"10.3389/fonc.2025.1657282","DOIUrl":"https://doi.org/10.3389/fonc.2025.1657282","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors have transformed non-small cell lung cancer (NSCLC) treatment, and while overall survival (OS) and progression-free survival (PFS) are well-established, a comprehensive meta-analysis focusing on complete response (CR) and pathological complete response (pCR) with tislelizumab-based therapies in NSCLC is lacking.</p><p><strong>Methods: </strong>This systematic review and meta-analysis was conducted following PRISMA guidelines. A thorough literature search was performed across PubMed, Embase, and Web of Science. We included both randomized controlled trials and observational studies of tislelizumab in NSCLC, focusing on extracting data for radiological complete response (CR, based on RECIST 1.1 criteria) and pathological complete response (pCR, defined as absence of residual invasive cancer in resected surgical specimens). Risk of bias was assessed using the Cochrane Collaboration's tool and the Newcastle-Ottawa Scale. Statistical analyses were performed using the 'meta' package in R. 95% confidence intervals (CIs) and odds ratios (ORs) were calculated for CR and pCR, and subgroup analyses were conducted.</p><p><strong>Results: </strong>7 studies were enrolled in the meta-analysis. The results on pCR showed significant heterogeneity (I² = 92.5%), with a random effects OR of 2.1103 (95% CI: 0.5195 to 8.5727). Subgroup analysis for pCR by disease type revealed a statistically significant difference between NSCLC and SCC only subgroups under the common effect model (p < 0.001). Furthermore, the pCR subgroup analysis by comparator drug showed a statistically significant difference (p < 0.0001) between Pembrolizumab+Chemotherapy (OR 0.6968, 95% CI: 0.3803 to 1.2767) and Chemotherapy alone (OR 7.3123, 95% CI: 2.9204 to 18.3092). For CR, the meta-analysis demonstrated minimal heterogeneity (I² = 0.0%), yielding a significant random effects OR of 2.6277 (95% CI: 1.2858 to 5.3699). Subgroup analysis for CR comparing tislelizumab plus chemotherapy to chemotherapy alone showed a significant advantage (OR 3.8690, 95% CI: 1.5423 to 9.7059).</p><p><strong>Conclusion: </strong>Tislelizumab combined with chemotherapy significantly improves CR rates in NSCLC compared to chemotherapy alone. While pCR data exhibit high heterogeneity, the findings highlight tislelizumab's role in achieving deep tumor responses.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1657282"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354371","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":"Case Report: Pathological diagnosis of left upper lobe nodules: two cases of composite small cell lung cancer and literature review.","authors":"Jishen Zhang, Defeng Jin, Yutao Wei","doi":"10.3389/fonc.2025.1629307","DOIUrl":"https://doi.org/10.3389/fonc.2025.1629307","url":null,"abstract":"<p><p>Combined Small Cell Lung Cancer (C-SCLC) is defined by the World Health Organization (WHO) as a combination of Small Cell Lung Cancer (SCLC) and other components, which may include any type of Non-Small Cell Lung Cancer (NSCLC). It is a relatively rare type of lung cancer, with an incidence ranging from 2% to 28%, and its incidence is on the rise. We report two cases of combined small cell lung cancer (C-SCLC) diagnosed by postoperative pathology following thoracoscopic left upper lobectomy at our hospital. One case was small cell carcinoma combined with squamous cell carcinoma (95% SCLC + 5% SCC), while the other was small cell carcinoma combined with large cell carcinoma. Both patients were male with a history of heavy smoking. Postoperatively, they received adjuvant chemotherapy combined with immunotherapy and surgery alone, respectively. No recurrence was observed during follow-up. This paper, in conjunction with a literature review, discusses the clinical and pathological features, diagnosis, potential molecular markers, treatment, and prognosis of C-SCLC. We emphasize the importance of early surgical resection and individualized comprehensive treatment, aiming to provide clinical reference for the diagnosis and management of this rare type of lung cancer.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1629307"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353883","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":"Incidental intraoperative discovery of a Wolffian tumor in a postmenopausal woman: a case report and literature review.","authors":"Dong-Mei Li, Ming-Rong Xi, Xi Zeng","doi":"10.3389/fonc.2025.1674008","DOIUrl":"https://doi.org/10.3389/fonc.2025.1674008","url":null,"abstract":"<p><strong>Background: </strong>Female adnexal tumor of Wolffian origin (FATWO) is an exceedingly rare gynecologic neoplasm characterized by nonspecific clinical manifestations and diagnostic challenges. This article presents a case of an incidentally discovered FATWO in a postmenopausal woman, with a literature review.</p><p><strong>Case presentation: </strong>A 54-year-old postmenopausal woman was found to have a 5.2-cm solid mass in the left adnexa during routine examination. Ultrasonography revealed a well-circumscribed lesion with detectable blood flow, while computed tomography (CT) scan suggested an ovarian origin. Tumor markers were within normal limits, and the patient remained asymptomatic. Single-port laparoscopic exploration identified a 5-cm solid ovarian nodule with an intact capsule. Intraoperative frozen section analysis suggested FATWO, prompting subsequent total hysterectomy with bilateral salpingo-oophorectomy. No adjuvant therapy was administered postoperatively, and the patient showed no evidence of disease progression during 1-year follow-up.</p><p><strong>Conclusion: </strong>FATWO exhibits a potentially malignant biological behavior. For postmenopausal patients, total hysterectomy with bilateral salpingo-oophorectomy is recommended. Postoperative management should be individualized. Current evidence regarding treatment strategies for reproductive-age patients remains limited, warranting further investigation to optimize clinical decision-making.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1674008"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354304","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":"Multiparametric MRI-based radiomics and deep learning for differentiating uterine serous carcinoma from endometrioid carcinoma: a multicenter retrospective study.","authors":"Yi Shen, Liping Liu, Shuang Ma, Xiaohua Ban, Shaoxian Chen, Zhuozhi Dai, Shaofan Lin, Kainan Huang, Xiaohui Duan, Daiying Lin","doi":"10.3389/fonc.2025.1655384","DOIUrl":"https://doi.org/10.3389/fonc.2025.1655384","url":null,"abstract":"<p><strong>Background: </strong>Uterine serous carcinoma (USC) and endometrioid endometrial carcinoma (EEC) are distinct subtypes of endometrial cancer with markedly different prognoses and management strategies. Accurate preoperative differentiation between USC and EEC is of great significance for tailoring surgical planning and adjuvant therapy.</p><p><strong>Purpose: </strong>To develop and validate a multiparametric MRI-based radiomics and deep learning (DL) model for preoperative distinguishing USC from EEC.</p><p><strong>Methods: </strong>A total of 210 patients (68 USCs and 142 EECs) from four hospitals who underwent preoperative MRI were enrolled in this retrospective study. Features from radiomics and deep learning were extracted using T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast enhanced MRI (CE-MRI). The least absolute shrinkage and selection operator (LASSO) analysis was employed to identify the most valuable features. Clinical-radiological characteristics, radiomics and DL features were constructed using a support vector machine (SVM) algorithm. The models were evaluated using receiver operating characteristic (ROC) and decision curve analysis (DCA).</p><p><strong>Results: </strong>The all-combined model of clinical-radiological characteristics, radiomics and DL features showed better discrimination ability than either alone. The all-combined model demonstrated superior classification performance, achieving an AUC of 0.957 (95% CI: 0.904-1.000) on the internal-testing set and an AUC of 0.880 (95% CI: 0.800-0.961) on the external-testing set. The DLR model demonstrated superior predictive performance compared to the clinical-radiological model, although the differences were not statistically significant in both the internal-testing set (AUC = 0.908 vs. 0.861, <i>p</i> = 0.504) and the external-testing set (AUC = 0.767 vs. 0.700, <i>p</i> = 0.499). The DCA revealed that the all-combined model illustrated the best overall net benefit in clinical application.</p><p><strong>Conclusion: </strong>The integrated model, combining multiparametric MRI-based radiomics, deep learning features, and clinical-radiological characteristics, may be utilized for the preoperative differentiation of USC from EEC.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1655384"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354351","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":"Lathyrol inhibits the proliferation of Renca cells by altering expression of TGF-β/Smad pathway components and subsequently affecting the cell cycle.","authors":"Shengyou Song, Yalin Song","doi":"10.3389/fonc.2025.1629962","DOIUrl":"https://doi.org/10.3389/fonc.2025.1629962","url":null,"abstract":"<p><strong>Background: </strong>Renal cell carcinoma (RCC) is a prevalent type of malignant tumor with high morbidity and mortality. The TGF-β/Smad signaling pathway plays a significant role in the development and progression of RCC.</p><p><strong>Methods: </strong>This study explored the effects of lathyrol on the proliferation of Renca mouse RCC cells through the inhibition of the TGF-β/Smad signaling pathway and cell cycle arrest. Bioinformatics analysis, cell culture experiments, and animal experiments were conducted to determine the effects of lathyrol on the activity, mRNA expression, and protein expression of RCC cells and RCC xenograft tumors, as well as the expression of cell cycle and cell cycle regulatory proteins.</p><p><strong>Results: </strong>Lathyrol treatment was positively correlated with the inhibitory effect on cell proliferation. The IC values of 786-O cells and Renca cells were comparable. <i>In vitro</i>, lathyrol promoted both protein and mRNA expression of TGF-β1 while increasing Smad6 protein expression and Smad2, Smad3, and Smad4 mRNA expression; concurrently, it suppressed the protein expression of Smad2, Smad3, Smad4, and Smad9. <i>In vivo</i>, lathyrol suppressed the mRNA and protein expression of TGF-β1, TGF-βR1, Smad2, Smad3, Smad4, and Smad9 in RCC xenografts; promoted the protein expression of Smad6; and decreased the protein expression of cyclin D1, cyclin B1, cyclin A1, cyclin E1, CDK6, CDK4, and CDK1 while increasing the expression of P16, P21, and P27.</p><p><strong>Conclusion: </strong>Lathyrol can repress the expression of key proteins in the TGF-β/Smad signaling pathway, impede signal transduction, arrest the cell cycle progression of Renca cells, and subsequently inhibit the proliferation of RCC cells. Future studies are needed to further explore the mechanism of lathyrol in RCC treatment.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1629962"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12541422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354385","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":"From miRNA sponges to mTOR blockades: mapping the multidimensional landscape of ameloblastoma pathogenesis and precision targeting.","authors":"Jingsong Mao, Qingxuan Gai, Xinling Bao, Ming Zhong","doi":"10.3389/fonc.2025.1651236","DOIUrl":"https://doi.org/10.3389/fonc.2025.1651236","url":null,"abstract":"<p><strong>Background: </strong>Ameloblastoma is a benign but locally aggressive odontogenic tumor with frequent recurrence after conservative surgery. Evidence accumulated since 2010 implicates dysregulated non-coding RNAs (ncRNAs)-notably microRNAs (miRNAs) and circular RNAs (circRNAs)-as higher-order regulators of oncogenic signaling.</p><p><strong>Objective: </strong>This study aimed to synthesize peer-reviewed mechanistic and translational evidence on ncRNA networks in ameloblastoma, with explicit grading by evidence tier and emphasis on druggable nodes.</p><p><strong>Methods: </strong>We conducted a structured narrative search of PubMed, Scopus, and Web of Science (January 2010-May 31, 2025) using controlled terms for \"ameloblastoma,\" \"microRNA,\" \"circRNA,\" and key pathways (MAPK, PI3K-Akt-mTOR, Wnt/β-catenin, IL-33/STAT3; Hippo/YAP-TAZ considered contextually). Peer-reviewed studies with experimental validation in ameloblastoma were prioritized, while purely computational predictions and unrelated tumor entities were excluded.</p><p><strong>Results: </strong>Across patient tissues, cell models, and limited <i>in vivo</i> studies, recurrent miRNA changes-i.e., loss of miR-524-5p, miR-141-3p, and miR-1-3p and gain of miR-29a-3p-converge on MAPK/ERK and PI3K-Akt-mTOR signaling. Loss of miR-524-5p derepresses IL-33/ST2, amplifying NF-κB/STAT3 and PI3K signaling (preclinical). miR-29a-3p targets CTNNBIP1 to reinforce Wnt/β-catenin (preclinical). miR-141-3p is anti-migratory and has been reported to upregulate NCAM1 in ameloblastoma models (preclinical). miR-1-3p restrains LAMP2-mediated autophagy (preclinical). Overexpressed circRNAs (e.g., circ-MAP3K7 and circ-HIPK3) can titrate tumor-suppressive miRNAs and sustain pathway activity (preclinical). No randomized clinical trials in ameloblastoma exist to date.</p><p><strong>Conclusions: </strong>A coherent ncRNA network appears to maintain druggable signaling convergence in ameloblastoma. Translation will require multicenter validation of the ncRNA biomarkers, early-phase trials testing rational MAPK-mTOR combinations with ncRNA modulation, and jaw-targeted delivery approaches. Claims herein are limited to peer-reviewed, ameloblastoma-relevant evidence.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1651236"},"PeriodicalIF":3.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354225","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}