Cancer metastasis reviews最新文献

{"title":"The role of Notch signalling and its crosstalk with oestrogen receptor signalling in breast cancer.","authors":"Aygun Azadova, Orkhan Isayev, Antonio Marco, Greg N Brooke","doi":"10.1007/s10555-026-10331-4","DOIUrl":"10.1007/s10555-026-10331-4","url":null,"abstract":"<p><p>Breast cancer (BCa) is the most frequently diagnosed malignancy in women worldwide, with approximately 70% of cases driven by oestrogen receptor alpha (ERα). Endocrine therapies aim to suppress ERα signalling activity and form the foundation of current therapeutic strategies. However, a substantial proportion of patients either fail to respond due to intrinsic resistance or acquire resistance over the course of the treatment. This resistance arises through a complex interplay of factors including crosstalk with other signalling pathways such as Notch. Notch signalling, essential for mammary gland development, is aberrantly activated in breast tumours, where it contributes to cancer stem cell maintenance, epithelial-mesenchymal transition, angiogenesis, and metastasis. Notch receptors exert context- and subtype-specific roles: Notch1 and 4 promote tumour aggressiveness, whereas Notch2 often exhibits tumour-suppressive roles. In ERα-positive BCa, ERα and Notch signalling cooperate to drive resistance, whereas in ERα-negative disease, Notch promotes stemness and angiogenesis. While anti-oestrogen therapies effectively inhibit tumour growth, they can paradoxically activate Notch signalling and promote therapeutic resistance. Co-targeting Notch alongside endocrine therapy has been proposed as a strategy to delay the onset of therapeutic resistance. However, clinical development of Notch inhibitors has been limited by toxicity associated with pan-Notch blockade. More selective approaches, such as paralogue-specific antibodies, transcription-complex disruption, rational drug combinations, and advanced delivery platforms, are under active development to overcome these limitations. This review outlines the ERα-Notch crosstalk in BCa and examines current and emerging strategies for targeting Notch to overcome endocrine resistance and improve clinical outcomes.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147535374","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":"Measurable residual disease testing in acute myeloid leukemia: current state, foundational models, and tools for future development.","authors":"Joseph Van Galen, Stephen D Willis, Ashish Bains, Sara H Small","doi":"10.1007/s10555-026-10322-5","DOIUrl":"10.1007/s10555-026-10322-5","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a lethal and rapidly progressive hematologic malignancy with high rates of relapse and treatment refractoriness. Management of AML is complicated by biological heterogeneity in a disease that is broadly defined by the clonal expansion of myeloblasts that otherwise play an important role in healthy marrow tissues. While subtypes of AML are increasingly defined by druggable driver mutations including FLT3-ITD, IDH1, IDH2, and NPM1, conventional chemotherapy and reduced intensity induction regimens (e.g., azacitidine-venetoclax) remain therapeutic backbones. One area of active development for personalization of AML treatment is the assessment of measurable residual disease (MRD). MRD testing in AML is complicated by uncertainty regarding the physiologic compartment of persistent and relapsing myeloblasts, and by increasing recognition of myeloid driver mutations in some healthy bone marrow states, such as clonal hematopoiesis of indeterminate potential (CHIP). Even in large academic centers, MRD tools are not yet universally available. Standardized workflows for MRD implementation are only beginning to enter consensus and guideline documents. Current understanding of AML biology and state-of-the-art tools for MRD measurement are reviewed here in an effort to promote clinical and laboratory investigator collaboration for the development of reliable tools for improving outcomes in this deadly disease. Clinical trial number: not applicable.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147535404","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":"From stress to strength: mechanotransducing poly(aneu)ploidy into a community-level advantage in cancer.","authors":"Víctor Herrera-Fernández, Paul Dremsek, Markus Hengstschläger, Alexis J Lomakin","doi":"10.1007/s10555-026-10330-5","DOIUrl":"10.1007/s10555-026-10330-5","url":null,"abstract":"<p><p>Poly(aneu)ploidy is a potent source of cellular stress that typically leads to loss of fitness, premature aging/senescence, and cell death. Yet in some systems, most notably microbial pathogens and human cancer cells under poly(aneu)ploidogenic stress, cells can adaptively remodel their phenotype, resist damage, and even convert this stress into a selective advantage. This mini-review examines current knowledge on the mechanisms underlying these adaptive responses in cancer cell communities and how poly(aneu)ploid subpopulations reshape the behavior of the entire population. Because poly(aneu)ploidy is almost invariably coupled to changes in cell size and morphology, we place particular emphasis on biophysical and mechanobiological adaptations. These include physico-chemical reprogramming, proteome remodeling, volume gain, membrane stretching, altered endocytosis, community-level metabolic rewiring, engagement of the nucleus as a key mechanosensor, and the role of mechanoreceptor channels. Finally, we discuss emerging therapeutic strategies that seek to exploit the specific vulnerabilities of poly(aneu)ploid cells. Together, these insights highlight the central role of poly(aneu)ploidy in enabling tumor adaptation and evolution, and point to new avenues for understanding cancer cell biology and designing future treatment strategies.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13013109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518104","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":"Hyponatremia in cancer patients receiving immune checkpoint inhibitors: the ARON-MOUSEION-014 meta-analysis.","authors":"Elsa Vitale, Lorenza Maistrello, Francesco Ciccimarra, Alessandro Rizzo, Andrey Soares, Oronzo Brunetti, Veronica Mollica, Brigida Anna Maiorano, Mauro Francesco Pio Maiorano, Fernando Sabino Marques Monteiro, Francesco Massari, Matteo Santoni","doi":"10.1007/s10555-026-10327-0","DOIUrl":"10.1007/s10555-026-10327-0","url":null,"abstract":"<p><p>Hyponatremia is the most prevalent electrolyte imbalance in cancer patients. Symptoms potentially signaling hyponatremia include altered mental status, neurological condition, headache, nausea, dizziness, and balance loss. Its management is particularly challenging as it must account for prognosis, treatment-related factors, and quality of life, especially in individuals treated with immune checkpoint inhibitors (ICIs). This systematic review and meta-analysis assessed the incidence of hyponatremia in patients receiving ICIs or immune-based combinations compared with placebo or other anticancer treatments. The review was registered in PROSPERO (CRD420251137412). Eligible studies included randomized clinical trials, quasi-experimental, and observational studies reporting hyponatremia frequency in patients treated with ICIs. Risk of bias was assessed using the ROB 2 tool for randomized studies and ROBINS-I for observational studies. A meta-analysis for proportions was performed using generalized linear mixed models. Proportion was measured for any grade of hyponatremia, grade 1-2, and grade ≥ 3; and three separate subgroup meta-analyses were performed: one for any grade, one for grade 1 or 2, and one for grade ≥ 3. Thirteen studies were included in the quantitative analyses. Any-grade hyponatremia was reported in 7 studies (934 patients, 49 events), with a pooled prevalence of 5.0% (95% CI = [2.3%; 11.9%]; I² = 81.8%). Grade 1-2 hyponatremia was assessed in 7 studies (314 patients, 36 events) with a pooled prevalence of 1.2% (95% CI = [0.03%; 37.8%]; I² = 88.2%). Grade ≥ 3 hyponatremia was evaluated in 14 studies (652 patients, 35 events), yielding a pooled prevalence of 5.5% (95% CI = [3.1%; 9.6%]; I² = 44.8%). No significant small-study effects were detected for grade ≥ 3 events (Egger's test P = 0.313). These findings support routine electrolyte surveillance in patients treated with ICIs and highlight the need for further studies to clarify mechanisms and risk factors and define optimal monitoring strategies to improve both safety and outcomes.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147477818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuro-tumor interactions in peripheral tumors.","authors":"Xueshiyu Ma, Peixuan Ji, Jiahao Zheng, Shuqi Cai, Kan Xu, Yongwei Sun, Dejun Liu","doi":"10.1007/s10555-026-10321-6","DOIUrl":"10.1007/s10555-026-10321-6","url":null,"abstract":"<p><p>The nervous system is now recognized as a pivotal regulator of cancer, marking a paradigm shift that recasts nerves from passive bystanders to active drivers within the tumor microenvironment (TME). This review defines the \"neural niche,\" differentiating passive perineural invasion (PNI) from active tumor innervation. We examine how sympathetic signaling drives an \"angio-metabolic switch\" and immune evasion, whereas parasympathetic inputs exert context-dependent control over stemness and inflammation. We also highlight the underappreciated role of sensory neurons in promoting T-cell exhaustion via neuropeptides like calcitonin gene-related peptide (CGRP). Finally, we assess therapeutic strategies targeting neural dependence-from repurposing β-blockers to deploying nanotechnologies. Targeting neuro-tumor crosstalk offers a promising strategy to overcome therapeutic resistance and restore anti-tumor immunity.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147477863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the origins of childhood cancer.","authors":"Holly Holliday, Rebecca C Poulos","doi":"10.1007/s10555-026-10323-4","DOIUrl":"https://doi.org/10.1007/s10555-026-10323-4","url":null,"abstract":"","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic dependencies and neural progenitor dysregulation: driving forces in paediatric high-grade glioma development.","authors":"Yan Hay Grace Lee, Maria Tsoli, Yan Chuan Shi, Chi Kin Ip, David Ziegler","doi":"10.1007/s10555-026-10325-2","DOIUrl":"10.1007/s10555-026-10325-2","url":null,"abstract":"<p><p>Paediatric high-grade gliomas (pHGGs) are the most lethal brain tumours in children, characterised by profound epigenetic dysregulation and limited treatment options. The 2021 WHO Classification has established a molecular framework that distinguishes pHGGs as biologically distinct from adult glioblastoma, recognising four major subtypes: H3K27-altered diffuse midline glioma, H3G34-mutant diffuse hemispheric glioma, infant-type hemispheric glioma, and the rare IDH-mutant gliomas. Each subtype exhibits unique epigenetic landscapes, metabolic dependencies, and therapeutic vulnerabilities, necessitating subtype-specific treatment strategies. This review explores the molecular classification of pHGGs and examines the critical role of the tumour microenvironment in disease progression. We focus on glioma stem cells as central drivers of tumour initiation, maintenance, and therapeutic resistance, highlighting their remarkable cellular plasticity and ability to dynamically transition between different states. Particular attention is given to metabolic reprogramming in pHGGs, including alterations in glucose and lipid metabolism, and the exceptional metabolic flexibility of glioma stem cells that enables adaptation to microenvironmental pressures. Importantly, we discuss the intimate crosstalk between metabolism and epigenetic regulation, whereby metabolites serve as essential cofactors for chromatin-modifying enzymes-exemplified by α-ketoglutarate maintaining low H3K27me3 in H3K27M tumours and 2-hydroxyglutarate driving hypermethylation in IDH-mutant gliomas. We review preclinical models that have advanced pHGG research and discuss emerging immunotherapeutic approaches, including CAR T-cell therapies and oncolytic viruses. By synthesising current understanding of pHGG biology, this review aims to identify promising therapeutic avenues that exploit the unique metabolic and epigenetic vulnerabilities of each molecular subtype.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446405","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":"Early cellular plasticity promotes progression and dissemination in pancreatic adenocarcinoma.","authors":"Giulio Innamorati, Giorgio Malpeli, Luca Giacomello, Roberto Salvia, Thomas M Wilkie","doi":"10.1007/s10555-026-10326-1","DOIUrl":"10.1007/s10555-026-10326-1","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited therapeutic success and a persistently low 5-year survival rate. Despite significant advances in genomics and tumor biology, a fundamental challenge persists: to identify the elusive transformation from common benign pancreatic lesions to occasional malignant cellular identity. This review addresses a critical missing link in PDAC pathogenesis, focusing on when and where the switch to malignancy occurs, and why surgical intervention is often insufficient. We explore the biological and spatial-temporal evolution of precancerous lesions, such as PanINs and IPMNs, and examine how phenotypic plasticity and overlapping cellular programs-including squamous transdifferentiation, epithelial-to-mesenchymal transition (EMT), and acquisition of mesenchymal features-contribute to early dissemination, treatment resistance, and surgical failure. Recognizing and characterizing these early molecular events is essential for rethinking therapeutic strategies, identifying actionable biomarkers, and redefining the temporal window when curative intervention is feasible.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12979264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439023","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":"Dissecting the aberrant vasculature of glioblastoma: mechanisms and therapeutic targets.","authors":"Yinan Li, Yinfei Du, Fan Guan, Xuetong Li, Shu Cui, Wei Gao, Xinmiao Long, Minghua Wu","doi":"10.1007/s10555-026-10319-0","DOIUrl":"10.1007/s10555-026-10319-0","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a highly aggressive and almost incurable tumor of the central nervous system. The GBM microenvironment is infiltrated by numerous abnormal and heterogeneous blood vessels, forming a unique chaotic and irregular vascular network. These aberrant vessels not only disrupt the delivery of oxygen and nutrients but also play critical roles in the malignant invasion, immune evasion, and therapeutic resistance of GBM. In this review, we comprehensively discuss the morphological and functional alterations of the GBM vasculature compared with the normal blood-brain barrier, emphasizing the cellular and molecular mechanisms underlying abnormal vessel formation and their contributions to tumor progression. Furthermore, we provide an updated overview of current vascular-targeted therapies for GBM and explore potential future clinical therapeutic directions.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity and melanoma: unraveling the paradoxical survival benefit in immunotherapy.","authors":"Junjie Yang, Qingqing Hu, Chunyu Xue","doi":"10.1007/s10555-026-10324-3","DOIUrl":"10.1007/s10555-026-10324-3","url":null,"abstract":"<p><p>The incidence of melanoma has been steadily increasing worldwide, with metastatic disease accounting for a substantial proportion of melanoma-related deaths. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for advanced melanoma, yet patient responses remain highly variable. Interestingly, although obesity is a well-established risk factor for the development of melanoma, paradoxically, emerging clinical data reveal that obese patients may experience superior outcomes following ICI therapy-a phenomenon commonly referred to as the \"obesity paradox\". The biological mechanisms underpinning this paradox remain incompletely elucidated. This review synthesizes current evidence through a critical examination of methodologies used to define obesity in oncology research, followed by an exploration of mechanistic links between obesity and melanomagenesis. We subsequently summarize clinical evidence supporting the obesity paradox in melanoma immunotherapy and discuss potential immune-mediated and metabolic mechanisms underlying this paradoxical association. The review concludes by addressing translational implications of these findings for patient stratification and novel therapeutic strategies.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}