MedComm – Oncology最新文献_第8页

Local Anesthetics in Cancer: Mechanisms and Translational Perspectives 局部麻醉药在癌症中的应用：机制和翻译观点

IF 2.2

MedComm – Oncology Pub Date : 2026-01-16 DOI: 10.1002/mog2.70049

Wan-li Wang, Tu Huang, Yi-hang Hao, Min Zheng, Xin-hua Liang

{"title":"Local Anesthetics in Cancer: Mechanisms and Translational Perspectives","authors":"Wan-li Wang, Tu Huang, Yi-hang Hao, Min Zheng, Xin-hua Liang","doi":"10.1002/mog2.70049","DOIUrl":"10.1002/mog2.70049","url":null,"abstract":"Local anesthetics, such as lidocaine and ropivacaine, are fundamental to perioperative pain management. Beyond anesthesia, growing evidence indicates that local anesthetics may exert anticancer effects, potentially improving long-term oncologic outcomes by modulating tumor cell behavior and the perioperative environment. Surgery itself could promote metastasis via inflammatory and immunosuppressive pathways. However, the specific role and full therapeutic potential of local anesthetics in countering these effects are not fully defined. This review systematically synthesizes current understanding of the direct and indirect antitumor mechanisms of local anesthetics. We detail their direct inhibition of cancer cell proliferation through the induction of apoptosis and cell cycle arrest. The review also analyzes their indirect effects on the tumor microenvironment, which include enhancing antitumor immunity, attenuating surgery-induced stress and systemic inflammation, and inhibiting angiogenesis. We explore the potential synergy between local anesthetics and established cancer therapies, such as immunotherapy and targeted agents. Finally, the clinical evidence was appraised critically, discussing observational studies and the limited interventional trials linking regional anesthesia to improved survival, while addressing heterogeneity and confounding factors. By synthesizing mechanistic insights with clinical data, this review establishes a foundation for future research and highlights the translational potential of local anesthetics as adjuncts in perioperative cancer care.","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting Tumor Dormancy and Recurrence: Molecular Mechanisms and Peptide Therapeutic Delivery 靶向肿瘤休眠和复发：分子机制和肽治疗递送

IF 2.2

MedComm – Oncology Pub Date : 2026-01-04 DOI: 10.1002/mog2.70050

Abdur Raheem Aleem, Atif Ali, Wajid Ali, Yuying Cheng, Zhibin Yan, Chaoyi Xia, Chenguang Liu, Caiyun Fu, Yiren Hu, Xi Wang

{"title":"Targeting Tumor Dormancy and Recurrence: Molecular Mechanisms and Peptide Therapeutic Delivery","authors":"Abdur Raheem Aleem, Atif Ali, Wajid Ali, Yuying Cheng, Zhibin Yan, Chaoyi Xia, Chenguang Liu, Caiyun Fu, Yiren Hu, Xi Wang","doi":"10.1002/mog2.70050","DOIUrl":"10.1002/mog2.70050","url":null,"abstract":"Tumor dormancy is a clinically challenging but physiologically significant aspect of cancer development, characterized by disseminated tumor cells that persist in non-proliferative, quiescent state and frequently serving as a risk factor of recurrence. Although extensive progress has been made in understanding cancer progression and metastasis, strategies for reliably detecting and eliminating dormant tumor cells remain limited. This review aims to evaluate the current understanding of the molecular mechanisms underlying tumor dormancy, cellular quiscence, angiogenic processes, immune surveillance, and the complex roles of the tumor microenvironment, including extracellular matrix remodeling, metabolic adaptation and niche protection in tumor dormancy. Particular attention is given to the challenges associated with detecting and eliminating dormant cells, because these cells exhibit resistance to conventional therapies and reveal evasion of immune responses. Furthermore, we highlight peptide-based strategies as promising platforms for detection, modulation and elimination of dormant tumor cells. These include tumor-penetrating peptides, peptide-drug conjugates, self-assembling peptide nanostructures, and hydrogel–based delivery systems designed to disrupt dormancy-maintaining niches or sensitize dormant cells to therapeutic intervention. The review also provides a summary of recent preclinical and clinical developments in peptide-based treatments and outlines approaches to overcome translational challenges in targeting tumor dormancy. By integrating advances in peptide engineering with the biological principles of tumor dormancy, this review underscores the potential of peptide-based platforms to improve therapeutic outcomes and reduce cancer recurrence.","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crosstalk Between Cancer-Associated Fibroblasts and Immune Cells: Mechanisms and Therapeutic Implications 癌症相关成纤维细胞和免疫细胞之间的串扰：机制和治疗意义

IF 2.2

MedComm – Oncology Pub Date : 2025-12-14 DOI: 10.1002/mog2.70048

Ya Li, Xingpeng Di, Jiawei Chen, Jingwen Wei, Tianyue Li, Kunjie Wang, Banghua Liao, Deyi Luo

{"title":"Crosstalk Between Cancer-Associated Fibroblasts and Immune Cells: Mechanisms and Therapeutic Implications","authors":"Ya Li, Xingpeng Di, Jiawei Chen, Jingwen Wei, Tianyue Li, Kunjie Wang, Banghua Liao, Deyi Luo","doi":"10.1002/mog2.70048","DOIUrl":"https://doi.org/10.1002/mog2.70048","url":null,"abstract":"Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) interact with multiple immune cells, such as T cells, macrophages, neutrophils, and other immune cells, to display both antitumor or protumor effects. Despite enormous progress in immunotherapy, the CAF-associated resistance of immunotherapy is still urgent to be solved. In this review, we summarize the origins and heterogeneity of CAFs in the TME, including the subpopulations of CAFs and their biological function. Then we discuss the communications between CAFs and tumor-associated macrophages, T lymphocytes, tumor-associated neutrophils, and other immune cells. CAFs cannot only recruit immune cells in the TME, but also trigger polarization, proliferation, infiltration of immune cells, thereby promoting tumor progression. Inversely, some immune cells promote the recruitment, transdifferentiation, and proliferation of CAFs. We also focus on the current progress in therapeutic strategies targeting CAF-elimination, CAF-reprograming, downstream signaling blockade, and CAF-induced extracellular matrix barrier elimination to enhance the efficacy of immunotherapy and related clinical trials. Overall, we aim to provide the conceptions of CAF-immunocyte crosstalk in the TME and application of immunotherapy, paving the way for the development of precise and individualized strategies through clarifying the interaction between CAFs and immunocytes.","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decreased M6A Modification Promotes Progression of Gastrointestinal Stromal Tumor and KIT-Derived Imatinib Resistance Through FTO-Regulated Axis 减少M6A修饰通过fto调节轴促进胃肠道间质肿瘤进展和kit衍生的伊马替尼耐药

IF 2.2

MedComm – Oncology Pub Date : 2025-12-04 DOI: 10.1002/mog2.70047

Jiehan Li, Ge Zhang, Yizheng Zhang, Zhao Sun, Wunan Mi, Meimei Jiang, Guiyun Jia, Nannan Liu, Lingling Zhang, Zhenqiang Sun, Jianwu Jiang, Yingjie Zhang, Yang Fu

{"title":"Decreased M6A Modification Promotes Progression of Gastrointestinal Stromal Tumor and KIT-Derived Imatinib Resistance Through FTO-Regulated Axis","authors":"Jiehan Li, Ge Zhang, Yizheng Zhang, Zhao Sun, Wunan Mi, Meimei Jiang, Guiyun Jia, Nannan Liu, Lingling Zhang, Zhenqiang Sun, Jianwu Jiang, Yingjie Zhang, Yang Fu","doi":"10.1002/mog2.70047","DOIUrl":"https://doi.org/10.1002/mog2.70047","url":null,"abstract":"Imatinib (IM) is the first-line therapy for high-risk gastrointestinal stromal tumor (GIST) patients; however, over 50% of those with advanced stage or metastasis develop IM resistance within 2 years, and effective strategies to overcome this resistance remain elusive. In this study, we identified that decreased N6-methyladenosine (m6A) modification by the demethylase FTO regulated GIST progression and IM resistance. Long noncoding RNA XIST (XIST) was identified as the main demethylated RNA by FTO in GIST. FTO leaded to a decrease in m6A modification at the 10517-10633 site of XIST, thereby protecting it from degradation mediated by YTHDF2's recognition and binding. Stabilized XIST enhanced IM resistance by acting as a posttranscriptional regulator of KIT, the primary oncogenic driver in GIST. In vitro and in vivo functional assays confirmed the roles of both FTO and XIST in promoting GIST progression and IM resistance. Importantly, pharmacological inhibition of FTO using FB23-2 effectively restored IM sensitivity in murine xenograft models of GIST. Together, our findings establish a mechanistic link among FTO-mediated m6A demethylation, XIST stabilization, and posttranscriptional regulation of KIT in GIST. These insights highlight the therapeutic potential of targeting m6A-FTO axis to overcome IM resistance in GIST treatment.","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LncRNA SNHG5/miR-363-3p/USP28 Axis Promotes Lung Adenocarcinoma Progression Through Enhancing β-Catenin Stabilization LncRNA SNHG5/miR-363-3p/USP28轴通过增强β-Catenin稳定性促进肺腺癌进展

IF 2.2

MedComm – Oncology Pub Date : 2025-11-24 DOI: 10.1002/mog2.70046

Jia-yu Zou, Wen-min Zhou, Xue-bing He, Xing-tao Wu, Fang-de Li, Xiao-ci Luo, Xin Wang, Hong Bi, Li-ping Zhao, Xin-zhu Chen, Ming-na Sun, Yan-yan Yan, Jian-ye Zhang

{"title":"LncRNA SNHG5/miR-363-3p/USP28 Axis Promotes Lung Adenocarcinoma Progression Through Enhancing β-Catenin Stabilization","authors":"Jia-yu Zou, Wen-min Zhou, Xue-bing He, Xing-tao Wu, Fang-de Li, Xiao-ci Luo, Xin Wang, Hong Bi, Li-ping Zhao, Xin-zhu Chen, Ming-na Sun, Yan-yan Yan, Jian-ye Zhang","doi":"10.1002/mog2.70046","DOIUrl":"https://doi.org/10.1002/mog2.70046","url":null,"abstract":"Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, accounting for approximately 50% of global lung cancer-related mortality, which underscores the urgent need for identifying novel biomarkers and therapeutic targets. Long noncoding RNAs (lncRNAs) have been increasingly recognized as pivotal regulators in cancer development; however, the specific function of lncRNA small nucleolar RNA host gene 5 (SNHG5) in LUAD remained unclear. This study aimed to investigate the clinical significance, biological roles, and molecular mechanisms of SNHG5 in LUAD pathogenesis. Through integrated bioinformatics analysis and experimental validation, we found that SNHG5 was significantly upregulated in LUAD tissues and cell lines. Functional in vitro and in vivo assays—including gain-/loss-of-function studies, luciferase reporter assays, RNA immunoprecipitation, co-immunoprecipitation, and tumor xenograft models—demonstrated that SNHG5 promoted malignant phenotypes by acting as a competing endogenous RNA (ceRNA) for miR-363-3p. This sponge activity elevated the expression of ubiquitin-specific peptidase 28 (USP28), which in turn stabilized β-catenin and activated oncogenic signaling. Rescue experiments confirmed the functional importance of the SNHG5/miR-363-3p/USP28/β-catenin axis. In conclusion, these results indicate that SNHG5 drives LUAD progression through a novel ceRNA mechanism, highlighting its potential as both a prognostic biomarker and a therapeutic target.","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting Metabolic Reprogramming in Tumor: From Mechanisms to Precision Immunotherapies 肿瘤中靶向代谢重编程：从机制到精确免疫治疗

IF 2.2

MedComm – Oncology Pub Date : 2025-11-14 DOI: 10.1002/mog2.70045

Tong Zhang, Ping Gao, Linchong Sun

{"title":"Targeting Metabolic Reprogramming in Tumor: From Mechanisms to Precision Immunotherapies","authors":"Tong Zhang, Ping Gao, Linchong Sun","doi":"10.1002/mog2.70045","DOIUrl":"https://doi.org/10.1002/mog2.70045","url":null,"abstract":"Metabolic reprogramming is a core hallmark of malignant tumors. It facilitates the rapid growth of tumor cells and significantly modulates antitumour immune responses through metabolic interactions, affecting the success of immunotherapy. Despite recent breakthroughs in immunotherapy, most patients exhibit limited responses, and the underlying mechanisms are closely related to metabolic dysregulation within the tumor immune microenvironment. However, a comprehensive review of how to systematically leverage metabolic interventions to enhance immunotherapy efficacy is lacking. This review examines the competitive interactions between tumor and immune cells within essential metabolic pathways, including those involving glucose, amino acids, lipids, and nucleotides. This metabolic stress leads to the functional exhaustion of effector immune cells and activation of immunosuppressive cells, thereby promoting immune escape. Based on these mechanisms, we further summarize therapeutic strategies that target key metabolic enzymes to reshape the immune microenvironment and discuss their integration with strategies and clinical advances such as immune checkpoint blockade or CAR-T cell therapy. This review systematically integrates the core mechanisms and cutting-edge strategies at the intersection of metabolism and immunity, provides a theoretical framework and methodological reference for basic research and clinical translation in this area, and offers a theoretical basis and translational perspective for the development of synergistic metabolic–immunological therapeutic strategies.","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parkinson's Disease and Cancer: Mechanistic Insights and Therapeutic Opportunities From Cancer Neuroscience 帕金森氏病和癌症：来自癌症神经科学的机制见解和治疗机会

IF 2.2

MedComm – Oncology Pub Date : 2025-11-04 DOI: 10.1002/mog2.70044

Tianli Pan, Lin Yuan, Ruoyang Zhao, Liting Lu, Yinghao Zhi, Yuying Li, Min Wu, Yongye Huang

{"title":"Parkinson's Disease and Cancer: Mechanistic Insights and Therapeutic Opportunities From Cancer Neuroscience","authors":"Tianli Pan, Lin Yuan, Ruoyang Zhao, Liting Lu, Yinghao Zhi, Yuying Li, Min Wu, Yongye Huang","doi":"10.1002/mog2.70044","DOIUrl":"https://doi.org/10.1002/mog2.70044","url":null,"abstract":"There is a complex pathological association between neurodegenerative diseases and cancer. The epidemiological negative correlation between Parkinson's disease (PD) and brain tumor is particularly noteworthy. PD is characterized by the loss of dopaminergic neurons and the formation of Lewy bodies, while glioma, the representative of brain tumors, originates from the malignant transformation of glial cells. The molecular interaction network between these two diseases is elusive, limiting the development of cross-disease treatment strategies. This review systematically summarizes the associations between PD and glioma in genetic predispositions, epigenetic modifications, alterations in subcellular compartments, and cellular mechanisms concerning neurons, glial cells, and stem cells. Additional links arise from circadian rhythm regulation, oxidative stress, and gut microbiota, underscoring the importance of systemic pathways that connect neurodegeneration and tumorigenesis. Within this context, cancer neuroscience emerges as a critical framework, demonstrating how neuronal activity drives cancer progression by shaping the tumor microenvironment. Therapeutic opportunities build upon these mechanistic insights, including engineering neuron types to suppress cancer growth, modulating synaptic genes, inducing neuronal cell death cascades, and controlling inflammation to disrupt tumor-nerve crosstalk. Emerging neuroscience-inspired technologies may drastically expand the treatment landscape. This review tries to unveil a potential theoretical paradigm for developing precise therapies with both neuroprotection and antitumor effects.","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145469448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Breast Cancer Brain Metastasis: Bridging Biological Mechanisms to Therapeutic Innovations 乳腺癌脑转移：连接生物学机制与治疗创新

IF 2.2

MedComm – Oncology Pub Date : 2025-10-24 DOI: 10.1002/mog2.70043

Jing Feng, Yuwei Tao, Fengkai Li, Suling Liu

{"title":"Breast Cancer Brain Metastasis: Bridging Biological Mechanisms to Therapeutic Innovations","authors":"Jing Feng, Yuwei Tao, Fengkai Li, Suling Liu","doi":"10.1002/mog2.70043","DOIUrl":"https://doi.org/10.1002/mog2.70043","url":null,"abstract":"Breast cancer brain metastasis (BCBrM) remains a major clinical challenge with limited therapeutic options and poor prognosis. Despite advances in systemic therapy, the incidence of BCBrM is rising due to prolonged survival of patients with advanced breast cancer, yet effective brain-targeted strategies remain scarce, underscoring a critical research gap. This review integrates recent mechanistic insights that illuminate the complex biology underpinning BCBrM and explores how these discoveries are driving therapeutic innovation. We detail the metastatic cascade from local invasion to brain colonization, and examine key signaling pathways orchestrating brain-specific metastasis. Emphasis is placed on the dynamic crosstalk between tumor cells and the brain microenvironment, including astrocytes, microglia, and neurons, as well as metabolic reprogramming and immune evasion. We critically evaluate current preclinical models and their translational relevance, highlighting recent advances in humanized and imaging-based systems. Emerging therapies, such as central nervous system-penetrant kinase inhibitors, antibody–drug conjugates, and immunotherapies, are discussed alongside persistent challenges in drug delivery and resistance. Finally, we outline future directions, calling for cross-disciplinary collaboration and innovative clinical trial designs to personalize care and improve patient outcomes. Together, this review underscores the urgent need to bridge biology and therapy to transform the management of BCBrM.","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

O-GlcNAc Transferase Promotes Metabolic Dysfunction-Associated Steatotic Liver Disease-Related Hepatocellular Carcinoma by Facilitating the Degradation of PTEN O-GlcNAc转移酶通过促进PTEN的降解促进代谢功能障碍相关的脂肪变性肝病相关的肝细胞癌

IF 2.2

MedComm – Oncology Pub Date : 2025-10-14 DOI: 10.1002/mog2.70042

Haoran Liu, Suming Pu, Wenxin Zhu, Jing Huang, Jianming Li

{"title":"O-GlcNAc Transferase Promotes Metabolic Dysfunction-Associated Steatotic Liver Disease-Related Hepatocellular Carcinoma by Facilitating the Degradation of PTEN","authors":"Haoran Liu, Suming Pu, Wenxin Zhu, Jing Huang, Jianming Li","doi":"10.1002/mog2.70042","DOIUrl":"https://doi.org/10.1002/mog2.70042","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major risk factor for hepatocellular carcinoma (HCC), yet treatment options for advanced disease remain limited. O-GlcNAc transferase (OGT), the enzyme catalyzing O-GlcNAcylation, has been implicated in tumorigenesis, but its pro-cancer mechanism in MASLD-HCC remains poorly defined. Here, we show that OGT expression is significantly upregulated during MASLD-HCC progression and negatively regulates the tumor suppressor phosphatase and tensin homolog deleted on chromosome ten (PTEN) both in vivo and in vitro. Mechanistically, OGT catalyzes O-GlcNAcylation of PTEN at T382, which competitively inhibits the phosphorylation at the same residue. This modification promotes PTEN ubiquitination and accelerates its degradation. Importantly, O-GlcNAcylation of PTEN simultaneously impairs its intrinsic phospholipase activity. These dual effects compromise PTEN function, leading to activation of PI3K/Akt signaling pathway and enhanced tumor cell proliferation and migration. Moreover, pharmacological inhibition of OGT suppresses tumor growth and, when combined with PI3K/Akt pathway inhibitors, produces additive antitumor effects. These findings reveal a novel mechanism by which OGT-mediated O-GlcNAcylation destabilizes and inactivates PTEN, driving MASLD-HCC progression. They also highlight OGT and PTEN as promising therapeutic targets for developing novel strategies against HCC.","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145316903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Interplay of Aging and Cancer: Mechanisms, Implications, and Therapeutic Strategies 衰老和癌症的相互作用：机制、意义和治疗策略

IF 2.2

MedComm – Oncology Pub Date : 2025-09-17 DOI: 10.1002/mog2.70041

Liangce Wang, Yaru Luo, Xin Chen, Yuan Wang, Yan Zhang

{"title":"The Interplay of Aging and Cancer: Mechanisms, Implications, and Therapeutic Strategies","authors":"Liangce Wang, Yaru Luo, Xin Chen, Yuan Wang, Yan Zhang","doi":"10.1002/mog2.70041","DOIUrl":"https://doi.org/10.1002/mog2.70041","url":null,"abstract":"Aging is a complex biological process that significantly influences human health, including susceptibility to cancer. Although aging and cancer are distinct phenomena, they intersect through shared molecular mechanisms such as genomic instability, telomere attrition, epigenetic alterations, and chronic inflammation. Despite increasing recognition of these connections, how aging-related changes influence cancer development and treatment remains poorly understood. This review explores the intricate relationship between aging and cancer, highlighting how age-related changes in the tumor microenvironment, systemic inflammation and cellular senescence contribute to oncogenesis and tumor progression. We also assess the impact of aging on cancer treatment outcomes, as well as how cancer and its therapies may contribute to the acceleration of biological aging. Furthermore, we discuss potential intervention strategies that target the aging-related mechanisms that drive cancer development and progression. We review current progress and future directions in aging and cancer research, emphasizing that, with continuous technological advances and deepening insights, incorporating aging biology into oncology is both timely and necessary. By integrating recent advances in cancer biology and geroscience, this review offers insights critical for designing age-adapted therapeutic strategies. It underscores the need to shift toward personalized oncology approaches that account for the biological and clinical heterogeneity of aging.","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 3","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0