Critical reviews in oncology/hematology最新文献

{"title":"Disease-associated neutrophil heterogeneity in cancer therapy: Implications for precision immunotherapy","authors":"Dezhi Sui ,&nbsp;Fei Liu ,&nbsp;Linlin Zheng ,&nbsp;Shengjin Yu ,&nbsp;Zhe Ding ,&nbsp;Xiaoyu Ren ,&nbsp;Jiatong Gao ,&nbsp;Wenyan Wang ,&nbsp;Li Yang","doi":"10.1016/j.critrevonc.2026.105182","DOIUrl":"10.1016/j.critrevonc.2026.105182","url":null,"abstract":"<div><div>Neutrophils exhibit significant heterogeneity and functional plasticity in both healthy and disease states. Patients often suffer from multiple conditions simultaneously, complicating disease-associated neutrophil functions. This complexity challenges tumor-related research, yet current studies frequently overlook the functional differences of neutrophils across health and disease, which may contribute to unsatisfactory anti-tumor drug outcomes. This article reviews six conditions that affect neutrophil functions and influence tumor treatment efficacy: inflammation, aging, obesity, diabetes, thrombosis, and liver injury. It highlights how neutrophil phenotypes and functions change under these conditions, potentially altering their roles in tumor immunity and impacting anti-tumor therapies. Furthermore, four anti-tumor strategies targeting neutrophils are discussed, such as neutrophil drug delivery systems, neutrophil reprogramming, regulation of neutrophil extracellular traps, and the use of neutrophil membranes and exosomes. This review offers a novel perspective: for cancer patients with concurrent comorbidities (such as inflammation, aging, obesity, diabetes, thrombosis, and liver injury), tailoring treatment by targeting or leveraging neutrophils in these disease states may be of significant importance.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105182"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging trends and treatment strategies in ovarian cancer: A comprehensive review","authors":"B. Madhu Krishna ,&nbsp;Pankaj Garg ,&nbsp;Sravani Ramisetty ,&nbsp;Meera Nair ,&nbsp;Prakash Kulkarni ,&nbsp;David Horne ,&nbsp;Edward Wang ,&nbsp;Ravi Salgia ,&nbsp;Sharad S. Singhal","doi":"10.1016/j.critrevonc.2026.105177","DOIUrl":"10.1016/j.critrevonc.2026.105177","url":null,"abstract":"<div><div>Ovarian cancer (OC) is the eighth leading cause of cancer deaths in women globally, mainly originating from epithelial cells. It is further divided into type-I and type-II based on histology, molecular, clinical, and epidemiological characteristics. OC is commonly diagnosed in postmenopausal women, although this varies by ethnicity and genetics. Non-Hispanic white women have higher rates of OC, while African American women, despite lower incidence, are diagnosed at a younger median age. Family history and <strong>BR</strong>east <strong>CA</strong>ncer gene 1&amp;2 (BRCA1/BRCA2) mutations significantly correlate with a heightened risk of OC. Obesity, particularly from childhood, is associated with a higher risk of OC. Late menopause and smoking, are linked to a higher risk, especially for mucinous and possibly serous OC. Hormone-replacement-therapy, particularly with unopposed estrogen, also increases the risk of OC. Endometriosis raises the risk for specific subtypes like clear cell and endometrioid carcinoma. Women who have never given birth (null-parity) are at higher-risk for endometrioid and clear cell carcinoma. Surgical resection is crucial for reducing primary and local metastatic disease, involving inspection of the peritoneal cavity, cytology, lymph node removal, and biopsies. The success of surgery is limited by the visibility, extent, and tissue infiltration of the disease. The choice between neoadjuvant-chemotherapy and primary debulking surgery depends on patient health and tumor biology. Secondary cytoreductive surgery may be beneficial for platinum-sensitive recurrent OC. The use of PARP inhibitors and targeted therapies adds complexity to surgical decisions. Ongoing trials and new therapeutic strategies are expected to enhance the management and outcomes of OC.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105177"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROS-mediated therapeutic approach through oxidative stress and cell signalling modulation","authors":"Mridul Sahu ,&nbsp;Utkarsh Jain","doi":"10.1016/j.critrevonc.2026.105168","DOIUrl":"10.1016/j.critrevonc.2026.105168","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) are important modulators of cancer biology. Their functions vary depending on concentration and environment, ranging from stimulating tumour development to causing irreversible cell death. While higher ROS concentrations overwhelm antioxidant mechanisms and recruit stress-responsive that induces apoptosis, pyroptosis, autophagy, and other regulated cell death programs, basal to moderate levels of ROS benefit cancer cell growth, survival, and metastasis by activating redox-sensitive signalling pathways. Despite the fact that there is an abundance of literature on ROS in oncology, prior reviews frequently focus on particular signalling or antioxidant systems separately, failing to incorporate redox threshold dynamics, pathway cross-talk, and clinical translation. Through a pathway-oriented and mechanistically integrated examination of ROS-mediated cancer biology and treatments, this review aims to fill this gap. Small molecule ROS inducers, combinations with chemotherapy, radiation, and immunotherapy, and tumour-targeted delivery systems such as nanoparticles, prodrugs, and stimulus-responsive carriers are examples of recent advancements in ROS-directed therapy. By scientifically classifying ROS-modulating medicines according to the predominant signalling pathways and the level of evidence, this study critically investigates therapeutic approaches, translational constraints, and future directions of ROS-based cancer therapy. Additionally, it defines strategic priorities for the advancement of precision oncology and redox-targeted therapies.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105168"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signet-ring cell cytomorphology in breast cancer: Unveiling the overlooked","authors":"Shitong Su ,&nbsp;Zijian Liu ,&nbsp;Bifeng Yao ,&nbsp;Qiuyang Jing ,&nbsp;Ruijie Liu ,&nbsp;Kuansong Wang","doi":"10.1016/j.critrevonc.2026.105170","DOIUrl":"10.1016/j.critrevonc.2026.105170","url":null,"abstract":"<div><div>Signet-ring cell (SRC) cytomorphology in breast carcinomas involves cells distinguished by copious intracellular mucin that displaces the nucleus, imparting a characteristic signet-ring appearance. Although SRC terminology is prevalent within the context of gastrointestinal tumors, its recognition and management in breast cancer lack standardized clinical guidelines. The World Health Organization (WHO) classification of breast tumor does not recognize SRC differentiation in breast carcinoma as a discrete entity, noting the absence of distinct clinical or molecular characteristics. Consequently, many clinicians are unfamiliar with its identification and implications. This oversight might be influenced by the contentious nature of clinical outcomes associated with SRC. Notably, limited studies, including our case series, suggest that the presence of SRC differentiation may independently influence the biological behavior of the primary breast cancer subtype. Significant disparities between the primary tumor’s main body and its SRC component primarily involve molecular subtypes and aggressive behavior. Current literature on this subject is scarce and predominantly based on case reports and analyses with small cohorts, providing inadequate data to comprehensively address the phenomenon. This article aims to synthesize existing literature on SRC cytomorphology in breast cancer to provide a thorough review. Our analysis builds upon previous insights, introduces novel findings from our case series based on multicenter experiences, and incorporates original illustrations to enhance understanding of this pathology. The insights offered herein lay the groundwork for further research and aim to enrich the scholarly discourse surrounding SRC cytomorphology in breast cancer.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"220 ","pages":"Article 105170"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory mechanisms and functions of RORγt⁺ antigen-presenting cells in the tumor microenvironment of non-small cell lung cancer","authors":"Qingze Tan ,&nbsp;Weisong Zhang ,&nbsp;Yihao Wang ,&nbsp;Hao Wang ,&nbsp;Rongqi Guo ,&nbsp;Hao Zhu ,&nbsp;Dongxu Ying ,&nbsp;Yeting Li ,&nbsp;Xia Li ,&nbsp;Jianxiang Song","doi":"10.1016/j.critrevonc.2026.105142","DOIUrl":"10.1016/j.critrevonc.2026.105142","url":null,"abstract":"<div><div>Non–small cell lung cancer (NSCLC) shows heterogeneity in benefit from immunotherapy across stages and biomarkers, underscoring the need to define tumor-microenvironment (TME) circuits that shape immune activation, spatial organization, and adaptive resistance. Beyond classical APCs, an emerging family of MHC-II⁺, RORγt-expressing APCs—including group 3 innate lymphoid cells (ILC3s), extrathymic AIRE⁺ cells (eTACs), and DC-like populations—has been reported in barrier and lymphoid tissues, shaping type-3 immunity, Th17 differentiation, tolerance, and tertiary lymphoid structure (TLS) biology. Direct phenotypic and functional characterization of bona fide RORγt⁺ APCs in human NSCLC remains limited, and many tumor-derived signals more plausibly reflect RORC-associated, type-3–skewing APC programs rather than confirmed RORγt⁺ identities. In this hypothesis-driven review, we integrate RORγt-linked APC biology, Th17 plasticity, and NSCLC immunobiology to propose a “TME signaling–RORγt-related APC programs–Th17 axis.” To prevent terminology drift, we adopt an evidence-tiered framework distinguishing bona fide RORγt⁺ APCs from inferred RORγt-associated states, and we describe functional variation using module-based descriptors (APC-program–high vs tolerogenic/TLS-linked bias). We further outline how cytokine–chemokine modules—notably CCR6–CCL20—and spatial TLS niches might couple APC programs to Th17 positioning and downstream CD8⁺ T-cell immunity, while emphasizing context-dependent bidirectionality (immune-supportive vs tumor-promoting inflammation). Finally, we highlight two regulatory modules—hypoxia–lactate/adenosine and lipid-ligand tuning of the RORγt ligand-binding domain—as plausible upstream levers that could remodel antigen presentation and type-3 outputs. Translational implications—including RORγt agonism, TME remodeling, and stage-aware biomarker hypotheses with minimally invasive profiling in malignant pleural effusion—are presented as testable hypotheses requiring validation in stage-resolved human NSCLC cohorts and mechanistic studies.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105142"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative approaches to irinotecan-based therapies for glioblastoma: Advancements in drug delivery and combination strategies","authors":"Chou-Yi Hsu ,&nbsp;Mirza R. Baig ,&nbsp;Pareshkumar N. Patel ,&nbsp;Gunjan Singh ,&nbsp;Ihab M. Abdelrahim ,&nbsp;Monthar Kadhem ,&nbsp;Vimal Arora ,&nbsp;Venkata Ramana Maddula ,&nbsp;Priya Priyadarshini Nayak ,&nbsp;Muhammad Shahid Iqbal","doi":"10.1016/j.critrevonc.2026.105144","DOIUrl":"10.1016/j.critrevonc.2026.105144","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains one of the most lethal human malignancies, characterized by profound heterogeneity, therapeutic resistance, and limited drug penetration across the blood–brain barrier (BBB). Irinotecan (CPT-11), a topoisomerase I inhibitor converted to its active metabolite SN-38, has emerged as a potential chemotherapeutic alternative for GBM due to its distinct mechanism of action and non–cross-resistance with temozolomide (TMZ). However, early clinical trials revealed limited efficacy, largely constrained by subtherapeutic intratumoral exposure, pharmacogenetic variability, and systemic toxicity. Recent advances have redefined the therapeutic landscape of irinotecan through three convergent strategies: biomarker-guided precision, rational combination design, and innovative drug-delivery systems.</div><div>Biomarker studies have identified predictive indicators such as TIMP-1 expression, TDP1/TOP1 activity ratio, and EGFRvIII-associated replication stress, providing a framework for patient stratification and response prediction. Mechanistic research has expanded irinotecan’s therapeutic logic beyond DNA damage, uncovering roles in p21-mediated senescence and metabolic-epigenetic modulation when combined with checkpoint inhibitors or senolytic agents. Parallel innovations in delivery ranging from liposomal and nanoparticle formulations to implantable PLGA devices, peptide–drug conjugates, and MRI-guided convection-enhanced delivery have achieved sustained intraparenchymal SN-38 exposure while minimizing systemic burden.</div><div>Collectively, these developments mark a translational shift from empirical cytotoxic therapy toward a modular, precision-engineered platform. The integration of biomarker discovery, molecularly rational combinations, and locoregional delivery systems positions irinotecan as a key component of next-generation GBM treatment paradigms, with the potential to overcome historical barriers such as BBB impermeability and therapeutic resistance.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105144"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic utility of circulating tumor DNA in classical hodgkin lymphoma: A systematic review and individual participant data bayesian meta-analysis","authors":"Amirhossein Shahsavand ,&nbsp;Shayan Forghani ,&nbsp;Mohammad Amin Kharaghani ,&nbsp;Reza Samiee ,&nbsp;Rania A. Mekary ,&nbsp;Mohammad Mahdi Aliasghari ,&nbsp;Sajjad Fattahnia ,&nbsp;Mona Daghaieghi ,&nbsp;Mohammad Reza Rostami ,&nbsp;Tahereh Rostami ,&nbsp;Ghasem Janbabai","doi":"10.1016/j.critrevonc.2026.105154","DOIUrl":"10.1016/j.critrevonc.2026.105154","url":null,"abstract":"<div><div>Over 20 % of patients with Hodgkin lymphoma (HL) experience disease progression after initial treatment. We evaluated the prognostic utility of circulating tumor DNA (ctDNA) in HL patients. We systematically searched PubMed, Embase, the Cochrane Library, Scopus, and Web of Science up to March 22, 2025. Survival data were extracted from Kaplan–Meier curves and digitized to reconstruct individual patient-level datasets. We applied a hierarchical Bayesian model with weakly informative priors to estimate hazard ratios (HRs), restricted mean survival times (RMSTs), along with their 95 % credible intervals (CrI) up to five years for both progression-free survival (PFS) and overall survival (OS). Ten studies, including 1158 patients, were analyzed. Elevated baseline ctDNA was associated with inferior PFS (HR: 2.74; 95 % CrI: 1.30–5.75) and a 5-year RMST loss of 7.7 (1.2–17.3) months. Prognostic strength increased over time, with interim ctDNA positivity showing an HR of 5.99 (3.46–10.13; ΔRMST: 22.7 months; 12.9–33.2) and end-of-treatment ctDNA positivity showing an HR of 13.4 (3.97–41.87; ΔRMST: 39.2 months; 17.7–49.4). High baseline ctDNA was associated with worse OS (HR: 2.49; 1.07–5.80; ΔRMST: 11.6 months; 0.7–27.8). Similarly, positive ctDNA following treatment predicted worse OS (HR: 4.74; 1.60–14.47; ΔRMST: 16.2 months; 3.0–38.1). To conclude, in HL patients, a higher ctDNA concentration was associated with increased disease progression and mortality, with this association intensifying toward the end-of-treatment. Clinical implementation requires standardization of assay methods, validation of prognostic thresholds, and longitudinal assessment of the independent prognostic value of ctDNA.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105154"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-β-mediated suppression of NK cell function and targeting strategies in tumor immunotherapy","authors":"Bo Wang ,&nbsp;Jiacheng Bi","doi":"10.1016/j.critrevonc.2026.105141","DOIUrl":"10.1016/j.critrevonc.2026.105141","url":null,"abstract":"<div><div>Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system that can directly kill tumor cells or coordinate other immune cells to exert antitumor effects. Transforming growth factor-β (TGF-β) is a potent inhibitory cytokine in the tumor microenvironment (TME), and its suppression of NK-cell function is an important contributor to tumor immune evasion. TGF-β can inhibit NK-cell activation and effector functions, impair NK-cell proliferation and migration, and induce the conversion of NK cells into type 1 innate lymphoid cells (ILC1s). Therefore, blocking or “hijacking” TGF-β signalling is a promising strategy to enhance the therapeutic efficacy of NK-cell-based immunotherapy. In preclinical models and, to a lesser extent, in early-phase clinical trials of TGF-β pathway inhibitors, strategies to reverse TGF-β-mediated suppression mainly include delivery of small-molecule inhibitors and recombinant protein drugs targeting TGF-β and its signalling pathways, as well as genetic engineering of NK cells. This review summarizes TGF-β signal transduction, the antitumor biological functions of NK cells, the multifaceted inhibitory effects of TGF-β on NK cells within the TME, and NK-cell-based tumor immunotherapy approaches that target TGF-β. We further highlight the limitations of current strategies and point to future directions for more precise and controllable interventions.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105141"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why isn’t an oncogenic mutation in KRAS enough to induce and sustain transformation?","authors":"Juan Iovanna ,&nbsp;Nelson Dusetti","doi":"10.1016/j.critrevonc.2025.105110","DOIUrl":"10.1016/j.critrevonc.2025.105110","url":null,"abstract":"<div><div><em>KRAS</em>, a key member of the <em>RAS</em> proto-oncogene family, encodes a small GTPase involved in regulating cell proliferation, differentiation, and survival through signaling cascades such as MAPK/ERK, PI3K/AKT/mTOR, RalGEF/RalA/B, JAK/STAT3, and NF-κB. Although <em>KRAS</em> mutations, especially at codons 12, 13, or 61, lead to its activation and contribute to uncontrolled growth, these changes alone are not enough to fully transform a normal cell. <em>KRAS</em> activation requires cooperation with other genetic or epigenetic events, such as inactivation of <em>p53</em> or <em>p16</em>^{<em>INK4a</em>}, tumor suppressor genes to overcome critical cellular barriers, for example, senescence and apoptosis. This need for cooperation reflects the complexity of the oncogenic process, requiring simultaneous deregulation of multiple signaling pathways for malignant transformation. Indeed, in experimental models, mutant <em>KRAS</em> expression in normal cells often induces oncogene-induced senescence rather than unlimited proliferation. These findings highlight that <em>KRAS</em> functions more as an initiator of tumorigenesis than as an autonomous driver. Thus, in depth understanding of the genetic context in which <em>KRAS</em> operates is essential for the development of effective and personalized therapeutic strategies.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105110"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extrachromosomal DNA as a dynamic engine of cancer evolution: Structure, plasticity and therapeutic resistance","authors":"Yan Gu ,&nbsp;Shuai Wang ,&nbsp;Yuxuan Xiao ,&nbsp;Yutao Li ,&nbsp;Lin Weng ,&nbsp;Kezhong Chen","doi":"10.1016/j.critrevonc.2026.105124","DOIUrl":"10.1016/j.critrevonc.2026.105124","url":null,"abstract":"<div><div>Extrachromosomal DNA (ecDNA) has become recognized as a common and influential form of oncogene and regulatory element amplification in human cancers. EcDNA consists of large, acentric circular DNA molecules that replicate autonomously. They frequently carry oncogenes, immune modulatory genes and enhancers, and they segregate in a non-Mendelian manner during mitosis. These properties support high transcriptional output, marked intratumoral heterogeneity and rapid adaptation. EcDNA has been proved that is associated with immune evasion, treatment resistance and poor prognosis. In this review, we bring together recent work to argue that ecDNA is better understood as a dynamic and selectable genomic subsystem rather than a static amplification artifact. First, we summarize current models of ecDNA formation, maintenance and structural plasticity. We then outline key functional features of ecDNA, such as oncogene amplification, enhancer hijacking, three-dimensional clustering into transcriptional hubs and epigenetic remodeling of cell states. Drawing on multi-region and longitudinal analyses, we distinguish between tumor lineage and circle lineage and describe how ecDNA architectures can define parallel evolutionary trajectories within and across lesions. We next consider how ecDNA behaves under therapeutic pressure and contributes to different cancer therapy through reversible copy number changes, pathway rewiring and non-genetic state transitions. Finally, we discuss recent advances in ecDNA detection from diverse data sources, potent clinical applications and early attempts to exploit ecDNA-specific vulnerabilities. Viewing ecDNA in this dynamic framework emphasizes its central role in cancer evolution and points to concrete opportunities to refine patient stratification and to develop strategies that selectively eliminate ecDNA-driven tumors.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"219 ","pages":"Article 105124"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}