Cancer metastasis reviews最新文献

{"title":"The diverse roles of Hox proteins in the regulation of the cell cycle and their therapeutic value in cancer treatment.","authors":"Lupeuea Vakafua, Lachlan Clifton-Bligh, Naisana Seyedasli","doi":"10.1007/s10555-026-10313-6","DOIUrl":"10.1007/s10555-026-10313-6","url":null,"abstract":"<p><p>Tissue morphogenesis and homeostasis occur at the interface of a fine coordination between cell cycle and differentiation events. The fundamental role of Hox genes during embryonic development is well established. However, less is known about their role in adult tissues and in contexts other than cellular differentiation. In this review, we focus on the role of Hox proteins in cell cycle-related events in adult tissues and highlight two main cell cycle-permissive and repressive roles for these genes. Given the significance of Hox proteins as a therapeutic target in cancer treatment, we will further discuss the existing approaches in this domain highlighting the challenges that impact the success prospects. For the successful development and application of Hox-oriented anticancer therapies, a comprehensive image of Hox roles in carcinogenic events including their mechanism of function as well as the networks/cascades within which they exert their effects is an inevitable requirement. Moreover, the functional variations of Hox genes in response to changes in the tumour microenvironment along with possible alternations of the mutational landscape in tumours during disease progression should also be taken into account as factors that might impact the therapeutic outcomes of Hox-targeting approaches.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 1","pages":"3"},"PeriodicalIF":8.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12804253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971641","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 fate of DYRK2 in cancer: balancing the light and dark side of tumorigenesis.","authors":"Lucía Suanes-Cobos, Miguel Torres-Ramos, Irene Aguilera-Ventura, Alejandra Serrano-Yubero, Marco A Calzado","doi":"10.1007/s10555-025-10311-0","DOIUrl":"10.1007/s10555-025-10311-0","url":null,"abstract":"<p><p>Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) is emerging as a pivotal player in cancer biology due to its pleiotropic cellular roles, functioning either as a tumor suppressor or an oncogene in a tissue- and genotype-dependent manner. DYRK2 regulates critical processes including cell cycle progression, DNA damage response, and stress signaling. As a tumor suppressor, DYRK2 facilitates the degradation of oncogenic proteins (e.g., c-Myc, SNAIL, TERT) and enhances apoptosis via p53 activation. Loss of DYRK2 has been associated with poor prognosis and chemoresistance in cancers such as colorectal, breast, and liver. Conversely, DYRK2 overexpression in certain tumors, including triple-negative breast cancer and ovarian carcinoma, supports oncogenic roles by enhancing proteasome function, promoting epithelial-mesenchymal transition, and contributing to therapy resistance. This functional dichotomy is modulated by post-translational modifications, microenvironmental stress, epigenetic regulation, subcellular localization, and interaction with protein complexes, underscoring the complexity of DYRK2 regulation. Therapeutically, DYRK2 represents a promising but context-sensitive target, with inhibitors showing efficacy in preclinical models of proteasome-addicted cancers, although precise biomarkers and cancer subtype stratification remain critical. Future directions include refining in vivo models and delineating the role of DYRK2 in cancer stem cell dynamics and immune modulation, emphasizing that understanding its context-dependent activity is essential to exploit its full therapeutic potential in oncology.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 1","pages":"2"},"PeriodicalIF":8.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12795908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954665","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":"Thrombocytosis in cancer patients: when more is not better-in fact, the opposite.","authors":"Karolina Aleksandrowicz, Barbara Polityńska, Joanna Kruszewska, Piotr Radziwon, Anna M Wojtukiewicz, Kenneth V Honn, Marek Z Wojtukiewicz","doi":"10.1007/s10555-025-10309-8","DOIUrl":"10.1007/s10555-025-10309-8","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Platelets are key elements of hemostasis which play an important role in pathological processes, especially in the context of cancer. They are small, disc-shaped structures equipped with a rich network of organelles and a cytoskeleton. In healthy individuals, the range of the platelet count is 150-350*10&lt;sup&gt;3&lt;/sup&gt;/uL. They contain numerous receptors that are responsible for diverse cellular responses triggered by physiological and pathological signals. The process of their production, known as thrombopoiesis, is regulated by many factors, which allows stem cells to transform into megakaryocytes and facilitates further platelet production. In the context of cancer, platelets play a special role in thrombosis, which is a common complication in cancer patients. Moreover, through the cytokines and adhesion molecules they secrete, cancers affect platelets, increasing their prothrombotic potential. Chemotherapy and radiotherapy can also damage blood vessels, promoting thrombosis. Platelets also support the process of cancer metastasis, affecting different stages of its evolution. By forming aggregates with cancer cells and leukocytes, they protect cancer cells from mechanical forces in the bloodstream and from recognition by the immune system. In addition, platelets secrete growth factors such as PDGF and TGF-β, which support cancer cell proliferation and angiogenesis, which in turn stimulates further tumor development. Leukocytes, enter into cooperation with platelets, supporting the adhesion of cancer cells to the vascular endothelium and facilitating their migration to distant tissues. A high platelet count is an unfavorable prognostic factor in many cancers, associated with poorer survival rates, a greater tendency to form metastases, and lower efficacy of anticancer treatment. Thrombocytosis is also associated with an increased risk of thrombotic complications in cancer patients, which requires intensive monitoring and antithrombotic prophylaxis. Platelets can also increase the resistance of cancer cells to chemotherapy and radiotherapy by supporting DNA repair in damaged cancer cells and protecting them from cytotoxic drugs. Surface receptors such as P-selectin and GP IIb/IIIa, facilitate platelets in forming aggregates with CTCs, which enhances their survival and promotes the formation of metastases. Intensive research is underway concerning the possibility of using antiplatelet therapy, such as the use of aspirin or P2Y12 receptor inhibitors, as potential methods for treating cancer patients. Some studies have shown that aspirin can prevent the formation of pre-metastatic niches, and P2Y12 inhibitors, such as clopidogrel, reduce the incidence of metastases in animal models. In addition, platelet apheresis is gaining importance as a therapeutic method in cancer, particularly in the case of thrombocytosis. In summary, platelets play an important role not only in hemostasis, but also in the development and progression of cancer, which make","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"45 1","pages":"1"},"PeriodicalIF":8.7,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12765752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902225","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":"One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.","authors":"Xuedi Cao, Yunyun Guo, Zhengyang Guo, Yang Liu, Yali Dou, Lixiang Xue","doi":"10.1007/s10555-025-10308-9","DOIUrl":"10.1007/s10555-025-10308-9","url":null,"abstract":"<p><p>One-carbon (1C) metabolism is a central metabolic network that supports nucleotide biosynthesis, amino acid metabolism, and redox homeostasis, playing a critical role in cellular proliferation. In cancer, dysregulation of this pathway fuels tumor progression by satisfying the heightened biosynthetic and energetic demands of malignant cells. Beyond their canonical metabolic roles, metabolites and enzymes within the one-carbon metabolic network exhibit moonlighting functions that contribute to tumorigenesis, immune evasion, and metastasis. These non-canonical functions include modulation of gene expression, epigenetic remodeling, and rewiring the oncogenic signaling pathways, underscoring their multifaceted roles in cancer biology. This review explores the production and utilization of one-carbon units, with a focus on the metabolic enzymes involved and their moonlighting functions in tumorigenesis. Additionally, we summarize the progress of ongoing clinical trials targeting the 1C network, highlighting the potential to exploit metabolic vulnerabilities for cancer therapy.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"44 4","pages":"91"},"PeriodicalIF":8.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12701874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752466","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":"Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.","authors":"Domenica Scordamaglia, Marianna Talia, Azzurra Zicarelli, Adelina Assunta Mondino, Salvatore De Rosis, Marika Di Dio, Francesca Silvestri, Chiara Meliti, Francesca Cirillo, Ernestina Marianna De Francesco, Roberta Malaguarnera, Carlo Capalbo, Marcello Maggiolini, Rosamaria Lappano","doi":"10.1007/s10555-025-10307-w","DOIUrl":"10.1007/s10555-025-10307-w","url":null,"abstract":"<p><p>Cell cycle dysregulation and the aberrant activation of cyclin-dependent kinases (CDKs) lead to uncontrolled cell proliferation; therefore, these events represent well-established hallmarks of cancer. The advent of CDK4/6 inhibitors, namely, palbociclib, ribociclib and abemaciclib, has changed the management of oestrogen receptor (ER)-positive/HER2-negative advanced breast tumours. The clinical success of these drugs for the treatment of breast cancer has encouraged diverse clinical trials aimed at exploring novel combinatorial regimens of CDK4/6 inhibitors in different types of tumours. Hence, a comprehensive understanding of the mechanisms of action of these agents is essential to extend their benefits. Emerging evidence suggests that CDK4/6 inhibitors exert antitumour activity through other mechanisms beyond the acknowledged ability to block the cell cycle, including the induction of stress response pathways, the reprogramming of cancer cell metabolism, the modulation of the tumour microenvironment, the enhancement of the antitumour immune responses and the reduction of immune evasion. Nonetheless, the acquired resistance to CDK4/6 inhibitors remains a major therapeutic challenge. Thus, the identification of molecular drivers involved in the resistance to these drugs is crucial for the design of novel therapeutic approaches and the selection of patient-centred strategies in various types of tumours.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"44 4","pages":"90"},"PeriodicalIF":8.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12701025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746388","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":"Ferroptosis at the intersection of radiotherapy and immunotherapy.","authors":"Gui-Xia Wei, Ya-Qin Zhao, Rong Tang, Hua-Shan Shi, Zhi-Ping Li","doi":"10.1007/s10555-025-10306-x","DOIUrl":"10.1007/s10555-025-10306-x","url":null,"abstract":"<p><p>Immunotherapy and radiotherapy are widely used in the treatments of various cancers. However, their application remains limited in certain cancer types because only a small number of patients respond to monotherapy. Notably, these two modalities can exert synergistic anti-cancer effects when combined. A growing body of evidence suggests that ferroptosis plays a crucial role in such combination therapies. Specifically, immunotherapy-activated CD8⁺ T cells and radiotherapy-induced ataxia-telangiectasia mutated gene (ATM) activation (associated with DNA damage) can synergistically enhance tumor lipid oxidation and induce ferroptosis, primarily through the inhibition of SLC7A11. Thus, ferroptosis inducers are emerging as a promising strategy to improve the efficacy of combination therapies. This review outlines the role of ferroptosis in radio-immunotherapy and summarizes recent advances in the field, and proposes new therapeutic strategies and research directions for cancer treatment. Ferroptosis inducers could significantly improve the efficacy of combination therapies and hold great potential for clinical translation. Furthermore, different radiotherapy fractionation regimens induce varying degrees of ferroptosis. Increasing single-fraction radiation doses can enhance lipid peroxidation and ferroptosis, suggesting a promising research direction for combining hypofractionation radiotherapy with ferroptosis inducers (FINs).</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"44 4","pages":"89"},"PeriodicalIF":8.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717196","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 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/s10555-025-10305-y","DOIUrl":"10.1007/s10555-025-10305-y","url":null,"abstract":"<p><p>Head and neck squamous cell cancers (HNSCC) are a clinically and biologically diverse group of malignancies with limited tools for real-time monitoring and early detection of recurrence. Liquid biopsy strategies-particularly the analysis of circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA)-have emerged as promising, minimally invasive biomarkers to capture real-time tumour dynamics. This review explores cellular and molecular processes that facilitate the release and survival of CTCs and ctDNA in the circulation in HNSCC. We also address the clinical relevance of CTCs and ctDNA in the prognosis, treatment response, and detection of minimal residual disease in HNSCC. Although integrating liquid biopsies into clinical care is limited by lack of standardisation, biological variability, and workflow challenges, CTCs and ctDNA have great potential to revolutionise HNSCC patient care with real-time and tailored interventions.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"44 4","pages":"88"},"PeriodicalIF":8.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145672607","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":"Spatial omics: applications and utility in profiling the tumor microenvironment.","authors":"Ji-Eun See, Sarah Barlow, Wani Arjumand, Hannah DuBose, Felipe Segato Dezem, Jasmine Plummer","doi":"10.1007/s10555-025-10304-z","DOIUrl":"10.1007/s10555-025-10304-z","url":null,"abstract":"<p><p>Spatial transcriptomics has emerged as a transformative technology in biomedical research, offering unprecedented insights into gene and protein expression within their native tissue context. Unlike conventional bulk or single-cell sequencing approaches, spatial omics has the advantage of preserving the spatial structure of tissues, allowing researchers to directly map molecular information onto histological structures. This review provides an overview of the current state of spatial omics technologies, highlighting their application in cancer research. Spatial omics has enabled detailed characterization of the tumor microenvironment (TME), revealing spatial heterogeneity, immune cell infiltration patterns, and complex mechanisms of tumor progression and therapy resistance across various cancer types. The review covers future directions, including artificial intelligence-driven analytics, improved standardization, and cost reduction to accelerate clinical translation. Ultimately, spatial omics is poised to play a central role in precision oncology, enabling a deeper understanding of tumor biology and informing more effective individualized treatment strategies.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"44 4","pages":"87"},"PeriodicalIF":8.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12672822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663521","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":"Advancing small cell lung cancer metastasis research: innovations in preclinical mouse models.","authors":"Qiqi Zhao, Liang Hu, Hongbin Ji","doi":"10.1007/s10555-025-10301-2","DOIUrl":"10.1007/s10555-025-10301-2","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) represents one of the most aggressive malignancies, featured with its extraordinary metastatic capacity. Preclinical mouse models have become indispensable systems for studying the molecular mechanisms underlying SCLC metastasis. This review summarizes recent advances in genetically engineered mouse models (GEMMs) and transplantation models for SCLC metastasis research, highlighting their unique advantages in investigating oncogenic drivers, tumor heterogeneity, immune interactions, and therapeutic responses. We further discuss emerging technologies capable of integrating with these models to advance both mechanistic and translational research. Lineage tracing and multi-omics approaches have provided unprecedented resolution in mapping clonal dynamics and phenotypic plasticity during SCLC metastasis. High-throughput in vivo screening has accelerated the systematic identification of novel metastasis regulators, and humanized mouse models offer clinically relevant systems for investigating human-specific tumor-immune interactions and supporting preclinical evaluation of immunotherapies. Collectively, these preclinical systems are reshaping our understanding of SCLC metastasis and providing powerful platforms to guide therapeutic discovery.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"44 4","pages":"86"},"PeriodicalIF":8.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644434","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":"Recent advances and treatment strategies in liver metastasis of pancreatic neuroendocrine tumors.","authors":"Zhiyuan Guo, Xu Han, Jilei Chen, Luyi Zhang, Jiahao Sun, Qinghan Li, Xishun Du, Fenglin Dong, Peng Xiu","doi":"10.1007/s10555-025-10303-0","DOIUrl":"10.1007/s10555-025-10303-0","url":null,"abstract":"<p><p>Pancreatic neuroendocrine tumors (pNETs) are characterized by significant spatial and temporal heterogeneity, exhibiting a wide spectrum of biological behaviors, histopathological features, and clinical presentations. The presence of liver metastases in pNETs is a critical prognostic factor that markedly alters the natural history of the disease and therapeutic outlook. Hepatic metastasis significantly influences treatment strategies, necessitating a multidisciplinary team (MDT) approach that integrates expertise from surgery, pathology, medical oncology, interventional radiology, and radiation oncology. Advances have been made in surgical resection, pharmacotherapy, interventional treatments, and radiotherapy. Evidence-based treatment paradigms tailored to different tumor grades and stages have been recommended by multiple specialty guidelines. This review summarizes recent progress in the field, covering topics such as the mechanisms underlying liver metastasis, advances in clinical research, controversies in surgical management, the role of neoadjuvant therapy prior to surgery, and options for non-surgical treatment modalities. It emphasizes the importance of regular MDT meetings to refine individualized treatment plans and to promptly address emerging challenges-such as treatment resistance and disease progression-with the ultimate goal of improving patient outcomes and quality of life.</p>","PeriodicalId":520582,"journal":{"name":"Cancer metastasis reviews","volume":"44 4","pages":"85"},"PeriodicalIF":8.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644442","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}