Cancer metastasis reviews最新文献

{"title":"Circadian clock control of breast cancer hallmarks: molecular mechanisms and therapeutic implications.","authors":"Luis Ricardo Hernández-Barrientos, Lorena Aguilar-Arnal","doi":"10.1007/s10555-026-10337-y","DOIUrl":"10.1007/s10555-026-10337-y","url":null,"abstract":"<p><p>Circadian rhythms regulate physiological functions and critical biological processes in almost all living forms. The circadian system enables organisms to anticipate and adapt to environmental fluctuations, thereby optimizing physiological responses. Proper synchronization between the master pacemaker in the brain and peripheral clocks throughout the organism is essential for maintaining homeostasis and promoting health. Conversely, circadian misalignment is increasingly recognized as a contributing factor in the pathogenesis of various diseases. Emerging evidence implicates circadian disruption as a driver of carcinogenesis. Indeed, epidemiological studies have associated night-shift work and chronic jet lag with an increased risk of cancer. At the molecular level, the biological clock comprises a complex network of transcriptional-translational feedback loops that generates approximately 24-h cycles in gene expression across all tissues. Notably, many clock-regulated genes participate in key pathways relevant to tumorigenesis, including cell cycle regulation, DNA damage repair, angiogenesis, and metabolism. Moreover, the circadian clock represents a promising therapeutic target in oncology. Numerous clinical trials have demonstrated that chronomodulation of chemotherapeutic agents can enhance treatment efficacy while mitigating adverse effects, thereby improving the quality of life for cancer patients. Hence, advancing our understanding of the molecular interplay between circadian regulation and cancer development may elucidate the role of circadian rhythms in tumorigenesis, facilitate the identification of novel prognostic markers and therapeutic targets, and ultimately improve outcomes in breast cancer patients.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848987","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":"Homeobox A10 in gastrointestinal malignancies: unraveling metastatic mechanisms and novel therapeutic opportunities.","authors":"Sophia G Kisling, Ashu Shah, Esther Johnson, Zahraa W Alsafwani, Venu Raman, Surinder K Batra","doi":"10.1007/s10555-026-10338-x","DOIUrl":"10.1007/s10555-026-10338-x","url":null,"abstract":"<p><p>Homeobox (HOX) genes are essential regulators of embryonic development and cellular differentiation under physiological conditions. Among this gene family, HOXA10 has emerged as a pivotal factor in gastrointestinal (GI) cancers, influencing tumor growth, metastasis, disease progression, and resistance to therapy. HOXA10 functions as a transcription factor and plays key roles not only in embryogenesis but also in immunomodulation. HOXA10 and its transcriptional targets play a crucial role in cancer development, promoting cell growth, invasion, migration, metastasis, and resistance to cell death. Recent studies have explored the influence of HOXA10 on the tumor immune microenvironment, particularly its role in modulating immune cell recruitment and signaling pathways that enable tumor immune evasion. Our recent research identified a HOXA10-regulated five-gene signature that distinguishes long-term from short-term survivors of pancreatic cancer, with HOXA10 expression correlating with increased regulatory T cell (T_reg) infiltration. HOXA10 impacts genes and pathways involving macrophages, Tregs, and other immune cells, potentially creating an immunosuppressive niche that promotes metastasis and diminishes the effectiveness of immunotherapies. In this review, we examine the diverse functions of HOXA10 in GI cancers, offering a comprehensive comparison with other HOX family proteins to elucidate their overlapping and distinct roles in malignancy. Our goal is to provide a thorough overview of how HOXA10 contributes to tumor development and its microenvironment. We highlight its critical role in facilitating cancer progression and metastasis, supported by data from cell lines, patient tumor samples, and clinical studies. Recognizing existing gaps in the understanding of HOXA10's role in cancer, we also explore potential strategies to target this gene, with an emphasis on synergistic approaches that combine HOXA10 inhibition and immunotherapy. Ultimately, these insights aim to identify vulnerabilities within GI cancers that could be exploited through novel therapeutic agents and combination treatments, paving the way for improved clinical outcomes.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849018","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":"Peritoneal cytology in pancreatic cancer: a comprehensive review on prognostic stratification and clinical decision-making.","authors":"Rui Wang, Senhao Liu, Junjie Ding, Yunwei Sun, Jin Zhou, Bing Peng, Zhong Wu","doi":"10.1007/s10555-026-10339-w","DOIUrl":"10.1007/s10555-026-10339-w","url":null,"abstract":"<p><p>Pancreatic cancer is characterized by its high malignancy, aggressive nature, and exceedingly poor prognosis. While surgical resection combined with systemic therapy offers the only potential for cure, the high recurrence rate significantly compromises long-term survival, even after radical surgery. The presence of peritoneal free tumor cells, detected via peritoneal cytology, represents a form of metastatic spread distinct from traditional distant metastases and exerts a similarly negative impact on patient outcomes. Peritoneal washing cytology is a practical and valuable diagnostic tool for identifying intraperitoneal free tumor cells, providing critical insights into disease progression and prognosis. Its status retains significant prognostic relevance even after initial clinical stratification based on resectability. Furthermore, peritoneal cytology plays a pivotal role in guiding clinical decision-making. Notably, the conversion from positive to negative cytology following preoperative therapy may select patients who could benefit from conversion surgery, potentially counteracting the adverse prognostic effects associated with peritoneal dissemination. This review comprehensively examines the etiology and risk factors associated with positive peritoneal cytology, integrates its prognostic value into current stratification systems, discusses its profound implications for clinical decision-making, explores emerging detection technologies, and shares future perspectives. By synthesizing existing evidence, this review aims to contribute to optimized individualized treatment approaches and improved clinical outcomes for patients with pancreatic cancer.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849008","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":"New biological insights into osteosarcoma-lessons from single cell sequencing studies.","authors":"Julia I Zehenter, Leo Kager, Sebastian K Eder, Sabine Taschner-Mandl, Snežana Hinić","doi":"10.1007/s10555-026-10336-z","DOIUrl":"10.1007/s10555-026-10336-z","url":null,"abstract":"<p><p>Osteosarcoma (OS), the most frequent primary malignant bone tumor in children and adolescents, is characterized by substantial inter- and intra-tumoral heterogeneity and an immunosuppressive tumor microenvironment (TME), constraining the efficacy of both standard chemotherapy and emerging immunotherapies. Recent advances in single-cell and single-nucleus RNA sequencing (scRNA-seq and snRNA-seq) have enabled high-resolution profiling of OS tumors, revealing diverse malignant, immune, and stromal cell populations. These studies have identified proliferative, inflammatory, and angiogenic tumor states, immunosuppressive myeloid subsets, exhausted T cells, and complex cell-cell communication networks that contribute to tumor progression and immune evasion. However, several challenges constrain the broader application of single-cell approaches in OS. The mineralized structure of bone tissue complicates dissociation into viable single cells, and the rarity of OS limits access to fresh specimens. Most existing datasets are based on small, heterogeneous cohorts and are generated using diverse protocols, which complicate data integration and comparison. Emerging methods are beginning to overcome these barriers. These include snRNA-seq for frozen and archival tissue, improved dissociation protocols for mineralized tumors, and integration with spatial transcriptomics to retain spatial context. Moving forward, combining single-cell transcriptomics with complementary modalities, such as immune repertoire analysis, chromatin accessibility profiling, and spatial proteo-genomics, combined with functional validation, will provide deeper insights into immune dynamics, regulatory mechanisms, and the cellular architecture of the OS TME. This review summarizes the current landscape of single-cell transcriptomics in OS and highlights methodological challenges in single-cell studies in OS tumors, recent biological insights, and their implication for immunotherapies.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848945","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 immunobiology of pancreatic cancer metastasis: premetastatic niche formation, organ-specific immune landscapes, and therapeutic opportunities.","authors":"Daniel R Principe","doi":"10.1007/s10555-026-10334-1","DOIUrl":"10.1007/s10555-026-10334-1","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is associated with poor overall survival and is largely refractory to standard therapies. Most patients present with locally advanced or metastatic disease, and those with early-stage tumors amenable to surgical resection face high rates of metastatic relapse. Despite the many successes of immunotherapy in other solid tumors, these approaches have shown only marginal activity in PDAC. In PDAC, metastasis occurs through a coordinated, multistep process characterized by a gradient loss of immune surveillance. This process begins with establishment of a receptive premetastatic niche, which occurs via conditioning of distant tissues by tumor-derived exosomes and the recruitment of myeloid cells, leading to extracellular matrix remodeling and local immunosuppression prior to metastatic dissemination. On arrival of metastatic cells, tissues undergo organ-specific immune editing with important implications for therapeutic vulnerability. Importantly, liver metastases maintain a profoundly immunosuppressive environment whereas lung metastases have higher immune activity. These observations challenge the prevailing assumption that insights from primary tumors are broadly applicable to metastatic disease, establishing metastatic PDAC as a distinct immunologic entity. This framework identifies unique therapeutic opportunities across the disease spectrum from early interventions targeting premetastatic niche formation to site-specific strategies for established metastatic disease.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848947","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":"Genetic characteristics and targeted treatments of primary bladder and urachal adenocarcinomas: a systematic review with pooled descriptive genomic analyses.","authors":"Bálint Dér, Melinda Váradi, Nikolett Nagy, Andras Kubik, Gladell P Paner, Gopa Iyer, Nadine T Gaisa, Sara E Wobker, Richard Bambury, Bas W G van Rhijn, Hikmat Al-Ahmadie, Péter Nyirády, Henning Reis, Tibor Szarvas","doi":"10.1007/s10555-026-10332-3","DOIUrl":"10.1007/s10555-026-10332-3","url":null,"abstract":"<p><p>Adenocarcinomas are rare histological subtypes of bladder cancer mainly presenting as primary bladder adenocarcinomas (PBACs), or urachal carcinomas (UrCs). The lack of standardized, evidence-based clinical recommendations for therapy results in individualized treatment decisions. These personalized treatments may be tailored based on molecular analyses to target driver mutations. The genetic background of UrC and PBAC has been increasingly explored through molecular analysis of relatively small case series. Similarly, experiences with targeted treatments are available from individual case reports and single institution case series. Consequently, currently available genetic and targeted treatment data are fragmented, hindering a comprehensive overview and firm conclusions. Therefore, we aimed to catalogue and interpret recent molecular genetic insights and targeted therapeutic experiences in UrC and PBAC in order to provide a basis for improved clinical decision-making. In this review, we screened online databases with search terms selective for genetic and targeted therapeutic data in UrC and PBAC. Utilizing the extracted data, we identified mutational frequencies, created OncoPrints, investigated signaling pathways, and evaluated treatment approaches guided by precision medicine. Our summary of genetic findings and targeted therapy strategies are intended to support off-label options for UrC and PBAC.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825935","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":"Evolving therapeutics in colorectal cancer peritoneal metastases.","authors":"Justin M Bader, Nicole Aguirre, Kurt S Schultz, Kwasi Ansere Ofori, Elizabeth Godfrey, Princy Gupta, Robert Tseng, Michael Cecchini, Raghav Sundar, Kiran Turaga","doi":"10.1007/s10555-026-10335-0","DOIUrl":"10.1007/s10555-026-10335-0","url":null,"abstract":"<p><p>Colorectal cancer peritoneal metastases (CRC-PM) are highly aggressive and present distinct therapeutic challenges. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have emerged as potential therapeutic approaches, but their roles remain controversial following recent clinical trials. This review summarizes the evolving landscape of CRC-PM management, including diagnostic challenges, conflicting views of CRS and HIPEC, systemic therapies and new treatment approaches, overview of recent and ongoing landmark clinical trials, and discussion of variations in societal and global guideline recommendations.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794975","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":"Correction to: Circulating tumour cells and circulating tumour DNA in head and neck cancer: from molecular insights to clinical impact.","authors":"Sreedevi Damodaran, Chameera Ekanayake Weeramange, Lizbeth Kenny, Sarju Vasani, Brett G M Hughes, Omar Breik, Chamindie Punyadeera","doi":"10.1007/s10555-026-10329-y","DOIUrl":"10.1007/s10555-026-10329-y","url":null,"abstract":"","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147625099","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":"Pexidartinib: Current advances in the symptomatic treatment of tenosynovial giant cell tumors.","authors":"Yulin Yuan, Zhuoer Zhang, Yanfeng Jiang, Ting Ye, Jing Chen","doi":"10.1007/s10555-026-10328-z","DOIUrl":"10.1007/s10555-026-10328-z","url":null,"abstract":"<p><p>Tenosynovial giant cell tumors (TGCTs), a rare benign mesenchymal neoplasm of synovial tissue, often incurs chronic pain, joint destruction and repeated surgery, markedly impairing quality of life. Historically, surgery was the only effective option. The colony-stimulating factor 1 receptor (CSF1R) inhibitor pexidartinib broke this therapeutic deadlock, pioneering systemic therapy and shaping subsequent drug development. Further exploration of pexidartinib and associated clinical studies in the field of TGCT have continued following its approval, with updated data and outcomes continuing to play a crucial role in guiding the clinical application of pexidartinib for treatment of TGCT. This review provides a comprehensive summary of the preclinical and clinical development of pexidartinib for treatment of TGCT, and highlights the recent updates in clinical studies and findings since its approval. These include long-term efficacy, optimization of therapeutic strategies, management of risks associated with long-term use, and real-world patient-reported outcomes, all of importance and value for patients and physicians in clinical practice. Here we aim to provide guidance for the improved clinical application of this drug class to enhance patient benefits in TGCT treatment.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597456","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":"Tumor exosomes impact functional hallmarks of cancer.","authors":"Mahdi Hejazi Laein, Yazhini Thinakaran, Maryam Katoueezadeh, Ranjith Iyappan, Jake Baker, Pazhanichamy Kalailingam, SoFong Cam Ngan, Neil E McCarthy, Panagiota Klentrou, Evangelia Litsa Tsiani, Siu Kwan Sze","doi":"10.1007/s10555-026-10333-2","DOIUrl":"10.1007/s10555-026-10333-2","url":null,"abstract":"<p><p>Cancer-derived extracellular vesicles (EVs), particularly exosomes, transfer oncogenic proteins, metabolites and nucleic acids to both nearby and distant cells. These diverse bioactive molecules act synergistically to promote cancer progression by simultaneously modulating multiple signaling networks in recipient cells. By inducing coordinated and complex molecular reprogramming, exosomes provide tumors with a powerful mechanism to drive the diverse processes required for malignant growth, invasion, metastasis and immune modulation. This review integrates recent and landmark studies from primary studies of tumor exosomes and how they influence critical features of cancer as defined in the updated 2022 Hallmarks of Cancer framework. Tumour-derived exosomes not only drive proliferative signalling and metabolic rewiring, but also actively reprogram the stromal and immune compartments of the tumour microenvironment and condition distant tissues to form metastatic niches. In particular, we focus on hypoxia-driven exosome biology. The low-oxygen conditions that characterize most solid tumors enhances exosomal biogenesis and selectively enriches cargo with active molecules to promote angiogenesis, cancer cell survival, epithelial-mesenchymal transition, immune evasion and metastasis. The hypoxia-conditioned exosomes act as long-range carriers of stress-adaptation signals, extending the influence of the hostile tumour microenvironment to diverse cell types. Furthermore, we examine emerging roles for tumor-derived exosomes in modulating host-microbial interactions and influencing the efficacy of immune checkpoint inhibitors, highlighting vesicle-mediated communication between tumors, the immune system, and polymorphic microbiomes. We also explore the potential of targeting exosome-mediated pathways for therapeutic and diagnostic applications. By mapping recent experimental findings onto the updated hallmarks of cancer, this review integrates the central role of exosomes in malignant progression and highlights their potential as therapeutic targets in the clinic.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 2","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13035603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583326","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}