MedComm – Oncology最新文献

{"title":"TLR7 Agonist Nanomedicine Suppresses Lung Metastasis of Osteosarcoma by Remodeling the Immune Microenvironment","authors":"Xinyue Zhang,&nbsp;Hao Zeng,&nbsp;Furong Qin,&nbsp;Yuquan Wei,&nbsp;Dandan Wan,&nbsp;Xiawei Wei","doi":"10.1002/mog2.70093","DOIUrl":"https://doi.org/10.1002/mog2.70093","url":null,"abstract":"<p>Osteosarcoma (OS) is an aggressive malignancy with high pulmonary metastatic potential, and effective therapies targeting metastasis and modulating the immunosuppressive tumor microenvironment are urgently needed. This study aimed to evaluate a TLR7 agonist liposome (1V209-Cho-Lip) for its anti-metastatic effects and mechanisms in OS. In both the OS tail-vein transplantation mouse model and orthotopic transplantation mouse model, 1V209-Cho-Lip significantly reduced the pulmonary metastatic burden and prolonged overall survival. Flow cytometry analysis revealed that 1V209-Cho-Lip intervention reshaped both pre-metastatic niche (PMN) and the immune microenvironment (IME) in lung tissue, and enhanced germinal center responses in tumor-drained lymph nodes, suggesting its ability to induce systemic anti-tumor immunity. Single-cell transcriptomics analysis further demonstrated that treatment with 1V209-Cho-Lip alleviates myeloid-mediated immunosuppression, promotes CD8⁺ T-cell activation and clonal expansion, and improves intercellular communication between tumor cells and immune cells. Moreover, 1V209-Cho-Lip showed significant synergistic effects when combined with anti-PD-1 antibodies or methotrexate (MTX), significantly enhancing the inhibition of metastatic progression and primary tumor growth. Taken together, comprehensive data indicate that 1V209-Cho-Lip acts as an immunomodulator with considerable translational potential, suitable for adjuvant therapy or combination regimens in the treatment of OS.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148848847","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}

{"title":"TRMT61A-Mediated m1A Modification Suppresses FDX1 Translation to Drive Cuproptosis Evasion and Radioresistance in Hepatocellular Carcinoma","authors":"Yunyun Xiao,&nbsp;Yue Li,&nbsp;Zelei Li,&nbsp;Rui Wang,&nbsp;Dongni Shi,&nbsp;Yanling Wen,&nbsp;Yibing Pan,&nbsp;Chen Lin,&nbsp;Junguo Bu,&nbsp;Libing Song,&nbsp;Hui Dai","doi":"10.1002/mog2.70092","DOIUrl":"https://doi.org/10.1002/mog2.70092","url":null,"abstract":"<p>Radioresistance remains a major obstacle to the curative treatment of hepatocellular carcinoma (HCC). While cuproptosis represents a potential strategy to eliminate resistant cells, the epitranscriptomic mechanisms underlying cuproptosis evasion remain unclear. Here, we identified tRNA methyltransferase 61 A (TRMT61A)-mediated N1-methyladenosine (m1A) modification as an important mediator of radioresistance by suppressing cuproptosis. m1A dot blot assays and immunohistochemical analyses revealed increased mRNA m1A levels and TRMT61A expression in radioresistant HCC tumors, correlating with poor clinical outcomes. Using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), RNA pull-down assays, and polysome profiling, we identified <i>FDX1</i> mRNA as a preferential TRMT61A target and found that TRMT61A-mediated m1A modification inhibited FDX1 protein production without altering mRNA abundance. RIP and luciferase reporter assays showed that YTHDF3 recognized m1A-modified <i>FDX1</i> transcripts and recruited eRF1 to repress translation. Functional assays revealed that FDX1 loss disrupted copper homeostasis and mitochondrial lipoylation, reducing radiotherapy-induced cuproptosis. Targeting TRMT61A with the small-molecule inhibitor CMP9 restored FDX1 translation, reactivated cuproptosis, and sensitized HCC tumors to radiotherapy in preclinical models, including patient-derived xenografts. This study highlights a previously unrecognized epitranscriptomic axis wherein TRMT61A-mediated m1A orchestrates cuproptosis evasion via translational repression of FDX1, and nominates TRMT61A-mediated m1A modification as a therapeutic target for radioresistant HCC.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148848622","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}

{"title":"Mitochondrial DNA in Tumor Evolution and Heterogeneity: Characteristics, Technological Advances, Applications and Challenges","authors":"Zifeng Ruan,&nbsp;Zihao Chen,&nbsp;Weicheng Yu,&nbsp;Maolei Zhang,&nbsp;Xingguo Liu","doi":"10.1002/mog2.70090","DOIUrl":"https://doi.org/10.1002/mog2.70090","url":null,"abstract":"<p>Tumor heterogeneity and Darwinian evolution act as core drivers of therapeutic resistance. Deciphering the phylogenetic architecture of cancer demands high-resolution lineage tracing. Nevertheless, exogenously introduced lineage markers possess inherent limitations. This review presents somatic mitochondrial DNA (mtDNA) mutations as a powerful, newly emerging endogenous lineage marker. It describes the unique characteristics of mtDNA, including high copy number, elevated mutation rate, and maternal inheritance modulated by random genetic drift, which support its function as a natural, high-resolution cellular barcode. It then summarizes critical technological breakthroughs for mtDNA mutation detection, particularly under single cell and spatial multi-omics frameworks. The central section integrates pioneering phylogenetic tree applications to clarify metastatic patterns, dissect resistance evolution, and correlate clonal history with phenotypic states. It also addresses ongoing methodological and interpretive obstacles, such as nuclear mitochondrial DNA segments (NUMTs) and functional consequences of mutations. Future directions include improving detection sensitivity, adopting long-read sequencing, and translating mtDNA lineage data into clinical strategies for minimal residual disease monitoring and adaptive therapy guidance. In summary, lineage tracing based on mtDNA mutations has become an indispensable tool, offering unprecedented insights into tumor biology and facilitating precision oncology advancement.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148848677","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}

{"title":"Nitric Oxide in Cancer: Mechanisms, Dual Role, and Therapeutic Strategies","authors":"Jia Shao,&nbsp;Honghua Zhang,&nbsp;Jingyu Chen,&nbsp;Ziyu Qian,&nbsp;Ning Zhang,&nbsp;Yihua Zhang,&nbsp;Hui Ye,&nbsp;Jianbing Wu,&nbsp;Zhangjian Huang","doi":"10.1002/mog2.70085","DOIUrl":"https://doi.org/10.1002/mog2.70085","url":null,"abstract":"<p>Nitric oxide (NO) is an endogenous gasotransmitter that influences cancer progression in a concentration-dependent manner, acting as either a tumor promoter or suppressor. Although this dual role is recognized, an integrated framework systematically linking its molecular mechanisms, immunomodulatory functions, and therapeutic translation is lacking, limiting rational design of NO-based anticancer interventions. This review analyzes the molecular basis of the concentration-dependent biphasic effects of NO, spanning canonical soluble guanylate cyclase-cyclic guanosine monophosphate (cGMP) signaling, protein S-nitrosylation (SNO), and peroxynitrite-driven nitrosative stress. It then examines how these signaling pathways drive the direct effects of NO on tumor cell proliferation, metabolism, angiogenesis, and therapy resistance. It further delineates how these effects, together with NO-mediated immunomodulation, define a dual role that encompasses both tumor cell-intrinsic processes and antitumor immunity across innate and adaptive compartments. The therapeutic translation of these mechanistic insights is examined through NO donor chemistry and the integration of such donors into stimulus-responsive delivery platforms, molecular conjugates, and combination regimens pairing NO with chemotherapy, radiotherapy, and immunotherapy. By connecting fundamental NO biology with emerging therapeutic strategies, this review offers an integrated framework to guide development of spatiotemporally controlled NO-based interventions and identifies translational bottlenecks requiring resolution for clinical application, including targeted delivery, controlled release kinetics, and context-dependent therapeutic windows.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753704","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}

{"title":"Adjuvant Targeted Immunotherapy Offers Short-Term Benefits for Resectable Hepatocellular Carcinoma But May Increase Late Recurrence Risk: Comparative Insights From the CARES-009 and IMbrave050 Trials","authors":"Shuanggang Chen,&nbsp;Lujun Shen,&nbsp;Letao Lin,&nbsp;Han Qi,&nbsp;Fei Cao,&nbsp;Lin Xie,&nbsp;Yujia Wang,&nbsp;Ruizhi Tang,&nbsp;Chen Li,&nbsp;Weijun Fan","doi":"10.1002/mog2.70089","DOIUrl":"https://doi.org/10.1002/mog2.70089","url":null,"abstract":"&lt;p&gt;Hepatocellular carcinoma (HCC) is the most common histological subtype of primary liver cancer and one of the leading causes of cancer-related death worldwide, imposing a heavy global public health burden, especially in HBV-endemic Asian regions. Surgical resection remains the gold-standard curative approach for patients with localized, resectable HCC, but high postoperative early and late recurrence rates persist as the dominant clinical barrier to durable long-term survival. Adjuvant targeted immunotherapy for resectable HCC has shown promising results in recent Phase 3 trials, but whether its short-term benefit translates into long-term survival improvement remains unclear [&lt;span&gt;1-3&lt;/span&gt;]. By systematically extracting and comparing the updated segmented longitudinal recurrence data from two pivotal global trials, IMbrave050 and CARES-009, we identify a consistent shared temporal efficacy pattern across distinct treatment platforms: powerful suppression of early postoperative recurrence within the first 1–2 years, followed by substantially attenuated protective effects or even reversed risk profiles in the late follow-up window, with a measurable potential rise in late recurrence risk among treated populations. This unique time-dependent efficacy shift has not been formally summarized or reported in previous cross-trial analyses, and it carries far-reaching guiding implications for postoperative clinical management and future adjuvant trial design in HCC.&lt;/p&gt;&lt;p&gt;The systemic adjuvant treatment landscape for resectable HCC has undergone dramatic iterative evolution over the past two decades, progressing from single-agent cytotoxic chemotherapy with limited anti-recurrence activity to single-agent molecular targeted therapy or immune checkpoint inhibitor monotherapy, and finally to synergistic targeted-immunotherapy combination regimens that currently dominate clinical research pipelines. Nevertheless, high-quality, long-term segmented follow-up data clarifying late recurrence risks after adjuvant combination therapy remain scarce across published trials. Most primary publications only report single time-point cumulative recurrence endpoints without dissecting separate early and late recurrence events, which creates an urgent clinical need for standardized cross-trial comparative analysis to extract unified long-term efficacy patterns shared by different perioperative therapeutic strategies.&lt;/p&gt;&lt;p&gt;In the IMbrave050 global multicenter trial, a prespecified interim analysis conducted at a median follow-up of 17.4 months demonstrated that this regimen significantly reduced early recurrence rates: the cumulative recurrence-free event rate reached 21% in patients receiving 12-month adjuvant atezolizumab plus bevacizumab, versus 32% in the active surveillance control group, confirming robust short-term disease control for high-risk resected HCC [&lt;span&gt;2&lt;/span&gt;]. At first mention of “Increased Event rate,” we define it as the proportion of patients","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753026","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}

{"title":"Long-Term Prognosis and Immunotranscriptomic Landscape in Esophageal Squamous Cell Carcinoma With Different Pathological Responses to Neoadjuvant Chemoradiotherapy: A Retrospective Cohort Study","authors":"Jianye Yuan,&nbsp;Zelin Weng,&nbsp;Xinke Zhang,&nbsp;Fangqi Deng,&nbsp;Zihui Tan,&nbsp;Jian Zhong,&nbsp;Rui Chen,&nbsp;Xiuying Xie,&nbsp;Xiaodan Lin,&nbsp;Ting Lin,&nbsp;Yan Huang,&nbsp;Qianwen Liu,&nbsp;Jing Wen,&nbsp;Jianhua Fu","doi":"10.1002/mog2.70087","DOIUrl":"https://doi.org/10.1002/mog2.70087","url":null,"abstract":"<p>Evidence is limited on long-term prognosis, and little is known about the immunotranscriptome in esophageal squamous cell carcinoma (ESCC) patients with different tumor regression grades (TRGs) after neoadjuvant chemoradiotherapy (NCRT) followed by surgery. Herein, the prognostic analysis of 300 ESCC patients treated with NCRT and surgery revealed that the TRG0/1 group (good responders) had significantly longer disease-free survival (DFS) and overall survival (OS) than the TRG2/3 group. Integrating TRG and pathological N-stage, we developed a tumor regression grade and lymph node (TRGN) staging system, which demonstrated superior prognostic stratification and distinct recurrence patterns. Transcriptome analysis showed that compared to the TRG2/3 group, the TRG0/1 group exhibited higher scores in immune checkpoint blockade (ICB) response-related signatures, greater similarity to ICB responder samples, and increased T-cell receptor clonality, suggesting enhanced immunotherapy sensitivity. Integrating scRNA-seq and RNA-seq, we identified B cell, CD8+ T cell, and NK cell subsets associated with better NCRT responses, within which a tight cell communication network potentially mediating antitumor immunity was formed. Multiplexed immunohistochemistry confirmed that the spatial relationship between CD8+ T/NK cells and tumor cells improved the NCRT response. These findings confirmed the prognostic value of TRGs and can help guide surveillance and treatment strategies in ESCC.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647733","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}

{"title":"Oxysterols in Cancer: From Biosynthesis and Pathophysiology to Targeted Therapeutics","authors":"Haili Shang,&nbsp;Yongsheng Li","doi":"10.1002/mog2.70088","DOIUrl":"https://doi.org/10.1002/mog2.70088","url":null,"abstract":"<p>Oxysterols are bioactive cholesterol oxidation products that link lipid metabolism, inflammation, immune regulation, and tumor progression. This review summarizes the generation, sensing, and cancer-related functions of major oxysterols, with a particular emphasis on 25-hydroxycholesterol and 27-hydroxycholesterol. It begins by outlining both enzymatic and non-enzymatic pathways for oxysterol production, as well as the key receptors and signaling pathways involved, including LXR, SREBP, ER, GPER, EBI2/GPR183, NF-κB, and PI3K/AKT/mTOR. The review then compares the ways in which oxysterols regulate tumor cell proliferation, invasion, metastasis, stromal remodeling, immune suppression, and therapeutic resistance across various malignancies, revealing a context-dependent duality of pro-tumorigenic and tumor-suppressive effects. Importantly, this review systematically evaluates pharmacological strategies that target oxysterol-producing enzymes, sensing receptors, and downstream signaling nodes. Emerging advances are highlighted, including the first in vivo validation of selective CYP27A1 blockade using Dafadine-A, Phase I clinical evaluations of LXR agonists demonstrating T cell expansion, GPR183-engineered CAR-T cells that exploit oxysterol gradients for enhanced tumor infiltration, and three preclinical combination frameworks that pair oxysterol pathway modulation with immune checkpoint blockade, targeted therapies, or metabolic multi-node strategies. By integrating mechanistic, preclinical, and clinically relevant evidence, this review clarifies how oxysterol biology may inform biomarker discovery, patient stratification, and future precision cancer therapy.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616273","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}

{"title":"Nanoparticle-Mediated Therapy for Glioma: Advances and Prospects","authors":"Wenqian Jiang,&nbsp;Jing Fei,&nbsp;Rangrang Fan,&nbsp;Haifeng Chen,&nbsp;Liangxue Zhou,&nbsp;Gang Guo","doi":"10.1002/mog2.70084","DOIUrl":"https://doi.org/10.1002/mog2.70084","url":null,"abstract":"<p>Glioma is one of the most invasive tumors in the central nervous system. Traditional treatment is limited by the blood-brain barrier and tumor drug resistance, and the prognosis of patients is very poor. At present, there is a lack of a comprehensive review that can systematically integrate various nanotechnology strategies to meet these challenges. This review first analyzes the brain biological barrier and glioma microenvironment that nanoparticles delivery must overcome. Furthermore, the key strategies for crossing these barriers, such as receptor-mediated transport and physical assistance methods, are systematically reviewed. This paper focuses on the design and characteristics of various nano-platforms (including inorganic, organic and biological nanoparticles), and discusses in detail how they can drive multimodal synergistic therapies such as chemotherapy, radiotherapy and immunotherapy to improve the curative effect and overcome drug resistance. The purpose of this paper is to provide an integrated perspective for researchers in the field to overcome the delivery barrier and realize innovative therapy by nanotechnology, and to provide a theoretical framework and design ideas for promoting the clinical transformation of the next generation of intelligent and personalized nano-drugs for glioma.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148466945","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}

{"title":"Prostate Cancer Development, Progression, and Therapy","authors":"Xin Jin,&nbsp;Zicheng Xiao,&nbsp;Zexian Ding,&nbsp;Wei Li,&nbsp;Ruijiang Zeng,&nbsp;Yujun Shuai,&nbsp;Weimin Ci,&nbsp;Dan Xia,&nbsp;Xu Zhang,&nbsp;Haojie Huang","doi":"10.1002/mog2.70082","DOIUrl":"https://doi.org/10.1002/mog2.70082","url":null,"abstract":"<p>Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death in men worldwide. Understanding the signaling pathways and molecular mechanisms that drive PCa development and progression is essential for developing new treatments. In this review, we provide an overview of the history and advancements in PCa's detection, diagnosis, surgical intervention, hormonal therapy, chemotherapy, and radiotherapy. We reviewed genetic alterations and their roles in PCa tumorigenesis. We also summarized the molecular mechanisms that drive the transition from castration‑sensitive PCa (CSPC) to castration‑resistant PCa (CRPC), along with factors that promote lineage plasticity from AR‑positive CRPC to neuroendocrine PCa (NEPC) and double‑negative PCa (DNPC). We further examined recent advances in immunotherapies, including CAR-T, PARP inhibitors, proteolysis-targeting chimeras (PROTACs), and antibody-drug conjugates (ADCs). Finally, we provide perspectives regarding the opportunities and challenges in detection, diagnosis, and therapy of PCa and future directions for the investigation of molecular mechanisms of prostate cancer development, progression, and therapy resistance. This review provides a framework that connects historical milestones with current molecular insights and offers a roadmap for future precision oncology strategies in prostate cancer.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148466710","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}

{"title":"Oxidative and Antioxidant Systems in Ferroptosis of Cancer: Mechanisms, Regulations, and Therapeutic Targeting","authors":"Deepak K,&nbsp;Pritam Kumar Roy,&nbsp;Maniklal Shee,&nbsp;Budhaditya Mukherjee,&nbsp;Aoife Ward Gahlawat,&nbsp;Mahitosh Mandal","doi":"10.1002/mog2.70083","DOIUrl":"https://doi.org/10.1002/mog2.70083","url":null,"abstract":"<p>Ferroptosis is a redox-governed, non-apoptotic cell death program driven by iron-dependent lipid peroxidation. Its execution depends on the balance between reactive oxygen species (ROS) generation and hierarchical antioxidant defenses. Despite extensive biochemical mapping, an integrated framework delineating how diverse redox defense systems converge to dictate ferroptotic sensitivity across tumor contexts remains lacking. This review delineates the hallmarks and molecular mechanisms of ferroptosis, examining how ROS sources within mitochondrial, the endoplasmic reticulum, membranes, and the cytoplasm drive lipid peroxidation. The antioxidant landscape is systematically classified into three functional tiers: (1) the primary canonical glutathione-GPX4 axis, (2) secondary non-canonical and radical-trapping systems including FSP1-CoQ10, GCH1-BH4, peroxiredoxins, and vitamin K, and (3) tertiary metabolic support and detoxification systems encompassing thioredoxin, AKR1C enzymes, SOD-catalase, and NADPH regeneration. The regulation of these defenses by master signaling hubs including NRF2, AMPK-mTOR, ATF4, STAT3, Wnt/beta-catenin, p53, and ncRNAs is evaluated, alongside oncogenic metabolic adaptations creating exploitable vulnerabilities in high-plasticity states including epithelial to mesenchymal transition, cancer stem cells, hypoxic, matrix-detached, and chemoresistant cells. Tumor microenvironment crosstalk among cancer-associated fibroblasts and immune effectors, including CD8⁺ T cells, natural killer cells, macrophages, and myeloid-derived suppressor cells, and therapeutic strategies spanning pharmacological and nanomaterial-based approaches are further examined. Collectively, this synthesis furnishes a mechanistic framework for precision exploitation of ferroptosis across oncological contexts.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"5 3","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148386113","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}