Cancer metastasis reviews最新文献

{"title":"Histotype and molecular subtype integration in epithelial ovarian cancer: implications for targeted treatment.","authors":"Shuyi Liu, Chaoyang Sun","doi":"10.1007/s10555-026-10385-4","DOIUrl":"10.1007/s10555-026-10385-4","url":null,"abstract":"<p><p>Ovarian cancer remains a major global health burden among women, ranking eighth in both cancer incidence and cancer mortality worldwide in 2024, with an estimated 330,731 new cases and 203,850 deaths. Epithelial ovarian cancer (EOC) accounts for more than 90% of ovarian cancers and comprises five major histological subtypes with distinct biological behavior, molecular alterations, and therapeutic vulnerabilities. However, most EOC histotypes continue to be managed primarily with surgery and platinum-based chemotherapy, underscoring the need to better define histotype-informed molecular targets and precision therapeutic strategies. This review summarizes the histological features, frequent molecular alterations, dysregulated signaling pathways, and clinically relevant protein-expression patterns across major EOC histotypes, with emphasis on their potential therapeutic implications. Representative clinical and preclinical evidence supporting histotype-specific targeted therapies is also discussed, with attention to differences in therapeutic actionability and evidence maturity. Building on this histotype-specific evidence, an integrated histotype-molecular therapeutic stratification framework covering five major EOC histotypes is proposed. By integrating histologic context with molecular profiling, this framework may help refine precision-guided therapeutic approaches and complement conventional management. Nevertheless, the clinical applicability and long-term benefits of therapies guided by this stratification framework remain to be confirmed in prospective studies.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 4","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217962","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":"Vascular plasticity in the gastric cancer environment: mechanisms, prognostic significance, and concepts of therapeutic interventions.","authors":"Magdalena Chmiela, Patrycja Jaroniek, Juan Carlos Rodríguez Manzaneque, Ewa Balcerczak, Marek Brzeziński, Agnieszka Jeleń, Saravanan Mani, Agnieszka Wosiak, Weronika Gonciarz","doi":"10.1007/s10555-026-10388-1","DOIUrl":"10.1007/s10555-026-10388-1","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a major global health problem because of its aggressive behavior and frequent development of therapeutic resistance. In GC, as in other malignancies, blood vessels are essential for Tumor-cell survival and dissemination, thereby facilitating metastasis to distant organs. As tumors grow, they remodel the surrounding microenvironment, generating hypoxic, acidic, nutrient-poor conditions with elevated interstitial fluid pressure. Reactive oxygen species further support tumor growth, glycolytic metabolism, and neovascularization. Highly aggressive cancer cells can also form endothelial cell-independent vascular-like networks defined as vasculogenic mimicry (VM), which may facilitate access to oxygen and nutrients. Many molecular markers and mechanisms underlying VM in GC remain insufficiently defined, while the presence of VM is associated with aggressive tumor behavior, metastatic potential, therapeutic resistance, and poor prognosis. Therefore, new therapeutic strategies are needed that complement conventional treatment and target the heterogeneous vascular compartments of GC. Nanomedicine may contribute to this goal by improving targeted drug delivery, local drug concentration, bioavailability, and controlled release while reducing systemic adverse effects.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 4","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217955","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":"Thymic epithelial tumors: what's next?","authors":"Li Zhang, Feiyue Zhang, Mahmoud Ismail, Gaofeng Li, Jens-C Rueckert","doi":"10.1007/s10555-026-10384-5","DOIUrl":"10.1007/s10555-026-10384-5","url":null,"abstract":"<p><p>Thymic epithelial tumors (TETs) are rare malignancies arising in an organ central to T cell development and immune tolerance, creating a distinctive interface between tumor biology and immunotherapy. Complete surgical resection remains the mainstay for resectable disease, whereas systemic treatment options for unresectable, recurrent, and metastatic TETs remain limited. The unique immunobiology of thymoma, particularly impaired central immune tolerance, may account for the unusual balance between antitumor activity and severe immune-related adverse events observed with immune checkpoint blockade. Recent molecular and immune profiling has begun to reveal biologically distinct TET subtypes and potential therapeutic vulnerabilities, including alterations in cell-cycle, PI3K/AKT/mTOR, RTK/RAS/MAPK, and DNA damage-response pathways, as well as epigenetic and immune regulatory mechanisms. Emerging strategies, including antibody-drug conjugates and biomarker-informed targeted and immune therapies, may expand systemic treatment options for advanced disease. This review examines these developments in the context of the distinctive biology of the thymus and highlights the key unanswered questions that may shape the next generation of TET research and treatment.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 4","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187559","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":"Mechanisms of systemic immune modulation in tumor development: Interactions across lymph nodes, bone marrow, and blood.","authors":"Xiaofei Yu, Linh Phạm, Tanja D de Gruijl, Marieke F Fransen, Febe van Maldegem","doi":"10.1007/s10555-026-10383-6","DOIUrl":"https://doi.org/10.1007/s10555-026-10383-6","url":null,"abstract":"<p><p>Cancer is a systemic disease in which the tumor interacts with the entirety of the body to promote tumor pathogenesis and progression. While tremendous efforts have focused on understanding the local immune responses in the primary site because of the noticeable immunosuppressive characteristics in the tumor microenvironment (TME), the interaction between the tumor and the host's systemic response has not received much attention. These interactions influence primary tumor growth and treatment responses and can further facilitate tumor dissemination and condition distant tissues for metastatic colonization. In this review, we summarize the reciprocal interactions between the primary tumor and the systemic environment throughout cancer development, including pre-metastatic niche formation and metastatic progression, with particular emphasis on tumor-draining lymph nodes (TDLNs), bone marrow (BM), and blood circulation. By integrating these perspectives, this review aims to provide a more comprehensive understanding of tumor development within the whole-body context, thereby highlighting the development and optimization of strategies in cancer diagnosis, prognosis, and treatment that account for the systemic nature of the disease.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 4","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122459","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":"Extracellular vesicles in breast cancer metastasis: functional insights and advances in single-EV analysis.","authors":"Yujin Lee, Yuling Wang, Peter Graham, Julia Beretov, Jie Ni","doi":"10.1007/s10555-026-10382-7","DOIUrl":"10.1007/s10555-026-10382-7","url":null,"abstract":"<p><p>Breast cancer (BC) metastasis remains a leading cause of mortality despite significant advances in screening and diagnosis. Extracellular vesicles (EVs), secreted by all living cells, carry biologically active cargo such as RNAs and proteins, playing a crucial role in cell-to-cell communication. Distinct EV subpopulations contribute to the tumour microenvironment, pre-metastatic niche formation, immune evasion, extracellular matrix remodelling, and ultimately promote BC organotropism. Beyond their biological roles, growing evidence highlights EVs as potential diagnostic and prognostic biomarkers, as well as viable therapeutic targets. However, the full scope of EV function in BC metastasis remains unclear, and their inherent heterogeneity and molecular complexity present considerable barriers to clinical translation. Addressing these challenges requires both a clear understanding of the distinct functions of each EV subpopulation and the application of advanced single-EV analysis techniques. In this review, we comprehensively examine the functional contributions of EV subpopulations to BC metastasis. Each RNA and protein cargo we discuss is assigned a graded evidence level. We further consider EV lipids, non-vesicular extracellular particles and current EV-directed therapeutic strategies. Finally, we highlight that single-EV analysis is a promising strategy to resolve this complexity and convert EV biology into clinically actionable biomarkers and targets.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 4","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043309","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":"The dual immune landscape of homologous recombination-deficient tumors: mechanisms and therapeutic implications.","authors":"Yiting Yang, Yujia Yin, Sheng Rong, Yujing Qian, Danning Li, Yingli Zhang, Xipeng Wang","doi":"10.1007/s10555-026-10380-9","DOIUrl":"10.1007/s10555-026-10380-9","url":null,"abstract":"<p><p>Homologous recombination deficiency (HRD) is a major genomic feature of several malignancies and provides a therapeutic rationale for DNA-damaging agents and PARP inhibitors. Beyond its role in genome instability, accumulating evidence suggests that HRD also reshapes the tumor microenvironment (TME). However, the immune consequences of HRD are not uniformly stimulatory. HRD-associated tumors may exhibit DNA damage-driven innate immune activation, increased interferon signaling, and enhanced antigen presentation, while simultaneously developing adaptive immune-evasive programs, including T-cell dysfunction, myeloid and regulatory T-cell recruitment, stromal remodeling, and vascular barriers to immune infiltration. In this review, we summarize current evidence linking HRD to immune activation and immune suppression across tumor types and propose a dual immune framework for understanding HRD-associated TME remodeling. We further discuss why HRD alone is insufficient to predict responses to immune checkpoint blockade and highlight emerging therapeutic strategies that integrate DNA damage response targeting with immune and stromal modulation.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 4","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032849","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":"Extracellular vesicles shape tumourigenesis: from signalling networks to systemic progression.","authors":"Stephanie B Telerman, Janusz Rak, Adam Telerman","doi":"10.1007/s10555-026-10377-4","DOIUrl":"10.1007/s10555-026-10377-4","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are established mediators of long-range intercellular communication in cancer, transferring oncogenic and regulatory cargo that reshapes recipient cells across tissues. Recent integrative multi-omics analyses of small EVs (sEVs) from healthy human donors consistently identify TSAP6/STEAP3 among the most abundant and reproducible sEV components, providing a physiological context for its role in sEV biology. Rather than acting solely as a downstream effector of p53, TSAP6 functions within a broader regulatory network by associating with TPT1/TCTP, which engages DDX3 and promotes the incorporation of RNAs, including microRNAs, into sEVs. The resulting p53-TSAP6-TCTP-DDX3 axis constitutes a wide-reaching regulatory system with non-cell-autonomous impact on cellular communication. Notably, TCTP sustains sEV-mediated signalling even in p53-mutant contexts. We suggest that these findings are consistent with other advances in cancer linking oncogenic transformation with EV biology. Together, these observations support regulated EV-mediated information transfer as a mechanism contributing to cancer progression and systemic cellular reprogramming. Conversely, reduction in EV abundance, altered cargo content, or signalling capacity may contribute to the activation of the tumour reversion programme in TCTP-dependent experimental models.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 4","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032923","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":"Precision therapeutic strategies for advanced gastrointestinal stromal tumors.","authors":"Akira Ooki, Hiroki Osumi, Keitaro Shimozaki, Shohei Udagawa, Kensei Yamaguchi","doi":"10.1007/s10555-026-10381-8","DOIUrl":"https://doi.org/10.1007/s10555-026-10381-8","url":null,"abstract":"<p><p>Gastrointestinal stromal tumors (GISTs), the most common mesenchymal neoplasms of the gastrointestinal tract, are molecularly heterogeneous diseases rather than a single entity. Activating mutations in KIT and PDGFRA define the dominant biological dependencies and establish tyrosine kinase inhibition as a therapeutic backbone. Imatinib, followed by later-line tyrosine kinase inhibitors, including sunitinib, regorafenib, ripretinib, and genotype-selected avapritinib, have substantially prolonged survival. However, durable disease control remains limited by clonal evolution, most notably, polyclonal secondary KIT mutations and lesion-to-lesion molecular heterogeneity. Molecular profiling using serial tissue and circulating tumor DNA analyses may improve precision care by identifying spatially and temporally evolving resistance mechanisms and guiding mutation-matched treatment selection. In this review, we summarize the biological and molecular landscape of advanced GIST, as well as the current therapeutic strategies and major mechanisms of resistance. Finally, we highlight promising therapeutic strategies supported by preclinical and clinical evidence that may advance subtype-informed precision medicine.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 4","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009654","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":"Castration-resistant prostate cancer as an adaptive tumor ecosystem: coupling tumor evolution with microenvironmental reprogramming.","authors":"Siliang Wang, Xinyi Xu, Minghuang Xu, Yuang Wei, Yunxiao Qiao, Xiaowen Song, Chuang Xie, Chunmei Zhou, Fuwen Yuan","doi":"10.1007/s10555-026-10379-2","DOIUrl":"https://doi.org/10.1007/s10555-026-10379-2","url":null,"abstract":"<p><p>Castration-resistant prostate cancer (CRPC) represents a lethal stage of prostate cancer that emerges following sustained androgen deprivation therapy (ADT) and remains a major clinical challenge in the era of androgen receptor (AR)-targeted therapies. Although AR reactivation and lineage plasticity are recognized as central mechanisms of resistance, these tumor-intrinsic processes alone cannot fully explain the profound heterogeneity and therapeutic failure observed during CRPC evolution. Here, integrating recent advances in single-cell and spatial profiling, we propose a unified framework in which CRPC is viewed as an adaptive tumor ecosystem shaped by evolutionary selection, cellular plasticity, and microenvironmental co-evolution under therapeutic pressure. ADT not only selects pre-existing resistant populations but also induces cellular reprogramming, expanding tumor state diversity and adaptive capacity. Concurrently, the tumor microenvironment is extensively remodeled to support and stabilize therapy-adapted states. Immune compartments evolve toward myeloid-dominant immunosuppressive configurations characterized by T cell dysfunction and exclusion, whereas cancer-associated fibroblasts (CAFs) promote tumor persistence through stromal remodeling, metabolic coupling, and alternative steroidogenic pathways. Neural remodeling represents an additional regulatory layer that enhances cellular plasticity, stress adaptation, and neuroendocrine differentiation. Together, these alterations establish a multicompartmental and self-reinforcing tumor-microenvironment network that sustains adaptation during AR suppression. This ecosystem framework further extends beyond the primary tumor to distal niches, including bone metastases and the gut microbiome, where tumor-osteoblast-osteoclast interactions and microbial regulation of androgen metabolism and immunity contribute to therapeutic adaptation. By integrating tumor evolution with immune, stromal, neural, and distal ecosystem remodeling, this perspective provides a system-level framework for understanding CRPC progression and highlights therapeutic strategies aimed at reprogramming or destabilizing adaptive tumor ecosystems rather than targeting individual resistance pathways alone.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 4","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984568","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":"Circulating Cell-free DNA as a biomarker for radiation-induced injury: From mechanistic insights to clinical translation.","authors":"Qixin Sun, Yikun Li, Tianwen Yin, Feifei Teng, Jinming Yu","doi":"10.1007/s10555-026-10374-7","DOIUrl":"10.1007/s10555-026-10374-7","url":null,"abstract":"<p><p>Circulating cell-free DNA (cfDNA) has attracted increasing attention as a minimally invasive biomarker for assessing radiation-induced tissue injury. Radiation exposure can alter cfDNA concentration, fragmentation profiles, and methylation patterns. These changes may reflect cellular damage, tissue origin, and temporal responses to irradiation. During radiotherapy, however, cfDNA can arise from tumor cells, irradiated normal tissues, endothelial cells, immune cells, and hematopoietic cells. This mixed origin complicates the interpretation of radiation-related signals. Current evidence is derived mainly from preclinical studies and small, heterogeneous clinical cohorts. Sampling schedules, analytical workflows, and clinical thresholds also vary across studies. Recent advances in fragmentomics, tissue-specific methylation analysis, mitochondrial cfDNA, multi-omics integration, and artificial intelligence have expanded the information obtained from cfDNA. In particular, tissue-specific methylation and fragmentation features may help identify the cellular or organ origin of injury. Nevertheless, prospective multicenter validation and methodological standardization are required before routine clinical use. This review summarizes the mechanisms linking radiation injury to cfDNA release, current detection technologies, and evidence for organ-specific applications. It also discusses clinical confounders, translational barriers, and future directions for integrating cfDNA into precision radiation oncology.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 4","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984567","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}