Seminars in cancer biology最新文献

{"title":"Tumor under forces: biophysical remodeling of tumor microenvironment and associated therapeutic opportunities.","authors":"Rashmita Luha, Gomathi Sankar, Siddhesh Saigaonkar, Suseel Mathusoothanan, Ajay Tijore","doi":"10.1016/j.semcancer.2026.102634","DOIUrl":"https://doi.org/10.1016/j.semcancer.2026.102634","url":null,"abstract":"<p><p>Tumors progress within a mechanically dynamic tumor microenvironment (TME), where extracellular matrix (ECM) stiffening, solid stress, and elevated interstitial fluid pressure remodel tumor cell and tumor-associated cell behavior. This TME-related mechanical remodeling often leads to tumor progression, metastasis and therapy resistance. In this review, we highlight recent advances in tumor mechanobiology, emphasizing how biophysical forces generated by cross-talk between tumor cells and tumor-associated cells precisely drive TME remodeling-ECM stiffening, hypoxia, leaky vasculature, invasion and therapy resistance-to support cancer progression. We discuss emerging interventions for selective tumor targeting that exploit the mechanical properties of the TME and biomechanical vulnerabilities of tumors and tumor-associated cells. Finally, this review explores the potential to leverage mechanobiological insights into the TME using New Approach Methodologies (NAMs), such as 3D bioprinted models and organ-on-chip platforms, coupled with AI-powered image analysis and modeling, to enable personalized cancer diagnosis and treatment.</p>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":" ","pages":"102634"},"PeriodicalIF":20.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision oncology in GI-cancers: Mechanisms of action, indications and ongoing strategies to overcome primary and secondary resistance","authors":"Laia Aceituno,&nbsp;Elena Valenzi,&nbsp;Oreste Segatto,&nbsp;Anna Saborowski,&nbsp;Arndt Vogel","doi":"10.1016/j.semcancer.2026.102619","DOIUrl":"10.1016/j.semcancer.2026.102619","url":null,"abstract":"<div><div>Gastrointestinal (GI) cancers remain a leading cause of cancer mortality, with durable benefit from current therapies limited to a subset of patients. Precision oncology is expanding options by targeting recurrent, actionable alterations, most notably in cholangiocarcinoma (CCA), in genes such as FGFR2, IDH1, KRAS, BRAF and ERBB2. Here, we review the evolving therapeutic landscape, emphasizing clinical efficacy, and indications for various treatment modalities. Key therapies include FGFR inhibitors (first and next-generation; both covalent and FGFR2-selective agents), IDH1 inhibitors, KRAS and BRAF inhibitors combined with EGFR blockade and/or chemotherapy, and HER2-targeted monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs). Central mechanisms of both primary and secondary resistance are detailed, with a focus on on-target mutations and convergent off-target MAPK signaling pathways. Finally, we discuss drug-tolerant persister cells, residual tumor cell states that survive therapy without canonical genetic resistance alterations and may contribute to relapse and secondary resistance.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"126 ","pages":"Article 102619"},"PeriodicalIF":20.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Drivers of Bidirectional Heart-Cancer Crosstalk: From a Relatively Tumor-Restrictive Myocardium to Therapeutic Decoupling.","authors":"Zili Tang, Rong Luo, Wanfeng Zhang, Xin Cao, Shun Lu, Xiaoping Li","doi":"10.1016/j.semcancer.2026.102621","DOIUrl":"https://doi.org/10.1016/j.semcancer.2026.102621","url":null,"abstract":"<p><p>Cardio-oncology has traditionally centered on treatment-related cardiotoxicity, yet cancer and cardiovascular disease influence one another before, during, and after therapy. This Review develops a direction-weighted staged framework for their metabolic interaction. We propose the healthy adult myocardium as a relatively tumor-restrictive environment in which metabolic reserve operates alongside mechanical, vascular, stromal, and immune constraints. Cancer can erode this reserve before overt cardiotoxicity through substrate redistribution, cachexia, mitochondrial stress, and circulating metabolites. Once metabolically injured, the heart can reshape immune, neurohumoral, metabolic, and vesicular signaling in ways that promote tumor progression; this heart-to-tumor direction constitutes reverse cardio-oncology within the broader bidirectional model. The proposed trajectory-from tumor-driven reserve loss to heart-derived reinforcement and subsequent stabilization or amplification-is common but not universal and may be reshaped by pre-existing cardiac disease or anticancer therapy. Evidence maturity differs across hubs: D-2-hydroxyglutarate provides the clearest source-defined tumor-to-heart proof of concept, whereas lactate handling and ferroptosis-related lipid-iron stress represent broader, testable, but less clinically resolved pathways. We translate these pathways into metabolic endotypes, provisional measurable criteria, and paired cardiac-oncologic endpoints to support therapeutic decoupling without compromising cancer control.</p>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":" ","pages":"102621"},"PeriodicalIF":20.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring glioblastoma microenvironment using organoids: opportunities, limitations, and emerging concepts","authors":"Anuja Lipsa ,&nbsp;Gaëlle Triballier ,&nbsp;Anna Golebiewska","doi":"10.1016/j.semcancer.2026.06.003","DOIUrl":"10.1016/j.semcancer.2026.06.003","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains the most lethal primary brain tumor in adults. These aggressive tumors evolve as dynamic, spatially organized ecosystems in which tumor cells continuously interact with the surrounding brain parenchyma and systemic environment. These reciprocal interactions actively drive invasion, therapeutic resistance, and ultimately, inevitable recurrence. Modelling this level of complexity has long required significant compromise. GBM organoids have emerged as a promising intermediate platform, bridging the gap between costly, low-throughput animal models and overly simplistic two-dimensional in vitro cultures. In this review, we summarize the diverse protocols currently used for GBM organoid derivation and long-term maintenance, focusing on the recapitulation of microenvironmental traits. We further discuss how these systems enable the investigation of tumor niche architecture and dynamic crosstalk with key components of the tumor microenvironment, including neural and immune elements, vascular-associated signals, and extracellular matrix cues. Although the inherent limitations of ex vivo systems must be carefully considered, increasingly advanced and well-designed protocols will enable robust interrogation of interactions within the GBM ecosystem and provide powerful platforms for therapeutic testing.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"123 ","pages":"Pages 44-60"},"PeriodicalIF":15.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special issue: Lipid metabolic alterations in cancer: Pathogenic mechanisms, therapies and common pathophysiology with cardiovascular disease","authors":"Joan Carles Escolà-Gil,&nbsp;Noemí Rotllan,&nbsp;Vicenta Llorente-Cortes","doi":"10.1016/j.semcancer.2026.06.001","DOIUrl":"10.1016/j.semcancer.2026.06.001","url":null,"abstract":"","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"123 ","pages":"Pages 40-43"},"PeriodicalIF":15.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microfluidic technologies for extracellular vesicle isolation and analysis: Implications for translational applications in cancer therapy","authors":"Fabrizio Mattei,&nbsp;Adriana Rosa Gambardella,&nbsp;Francesco Noto,&nbsp;Alessia Fiore,&nbsp;Andrea Pavesi,&nbsp;Giovanna Schiavoni","doi":"10.1016/j.semcancer.2026.06.002","DOIUrl":"10.1016/j.semcancer.2026.06.002","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are emerging as pivotal mediators of tumor progression, metastasis, and therapy resistance, reflecting the dynamic complexity of the tumor microenvironment. Their stability in biofluids makes EVs promising candidates for both tailored cancer therapies and liquid biopsy-based cancer diagnostics. However, their nanoscale size and molecular heterogeneity continue to challenge standardized isolation and analysis. Recent advances in microfluidic and organ-on-chip technologies are transforming EV research by enabling high-resolution separation, label-free detection, and real-time monitoring within physiologically relevant microenvironments. These platforms not only enhance analytical precision but also recapitulate tumor-stromal interactions that govern EV biogenesis, trafficking, and uptake. When coupled with complementary methods (such as immunoaffinity capture, size-exclusion chromatography, and viscoelastic or magnetophoretic sorting) microfluidic systems offer unprecedented control over EV isolation and characterization. Moreover, emerging wearable microfluidic devices and metabolic labeling strategies open new avenues for personalized EV delivery and nascent vesicle tracking in cancer models. Real-time monitoring of EV transfer between cancer and stromal cells within microfluidic environments further deepens our understanding of EV-mediated communication and its role in metastatic niche formation. In this review, we highlight the latest technological innovations and translational perspectives in EV isolation and analysis, emphasizing how microfluidic platforms are reshaping cancer diagnostics and therapy. Thanks to microfluidics, these integrated systems hold promise for accelerating the clinical deployment of EVs as functional biomarkers and therapeutic agents in precision oncology and nanomedicine-based cancer treatment.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"123 ","pages":"Pages 61-78"},"PeriodicalIF":20.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary trajectories of myelodysplastic syndromes/neoplasms","authors":"Maria Creignou ,&nbsp;Martina Sarchi ,&nbsp;Elsa Bernard ,&nbsp;Luca Malcovati","doi":"10.1016/j.semcancer.2026.01.006","DOIUrl":"10.1016/j.semcancer.2026.01.006","url":null,"abstract":"<div><div>Myelodysplastic syndromes/neoplasms (MDS) are a heterogeneous group of myeloid malignancies characterized by clonality, cytopenia, bone marrow dysplasia, and a variable risk of progression to acute myeloid leukemia (AML). With few therapeutic advances beyond the introduction of hypomethylating agents twenty years ago, MDS remains associated with poor overall survival, limited curative options, and frequent relapse or resistance to available treatments. Breakthroughs in genomic and single-cell technologies have transformed our understanding of MDS pathogenesis, revealing that disease initiation and progression follow stereotyped evolutionary trajectories driven by distinct constellations of somatic mutations and modulated by both endogenous and exogenous factors. In this review, we synthesize current knowledge of the genetic landscape of MDS and dissect the clonal path of the disease from precursor states to AML transformation. We further discuss how germline predisposition, bone marrow microenvironmental remodeling, and exposure to environmental or genotoxic stressors impact the selection, expansion, and transformation potential of the hematopoietic clone. Finally, we outline how these insights have underpinned a conceptual shift toward a molecular taxonomy of myeloid neoplasms, redefining diagnostic boundaries between MDS and AML, improving prognostic stratification, and enabling a biology-driven framework for personalized treatment of MDS.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"120 ","pages":"Pages 16-30"},"PeriodicalIF":15.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratumor heterogeneity and clonal evolution in sarcomas: Molecular, cellular, and functional drivers of therapy resistance","authors":"Thomas G.P. Grünewald ,&nbsp;Ina Oehme ,&nbsp;Johanna Wagner ,&nbsp;Stefan Fröhling","doi":"10.1016/j.semcancer.2026.02.001","DOIUrl":"10.1016/j.semcancer.2026.02.001","url":null,"abstract":"<div><div>Sarcomas, malignant neoplasms of mesenchymal origin, comprise more than 100 entities and numerous histologic subtypes. Their relative rarity compared with carcinomas, interpatient diversity, and pronounced intratumor heterogeneity (ITH) make sarcomas clinically challenging. Yet, they also provide excellent models for studying the molecular and cellular underpinnings of ITH and how it translates into diverse clinical outcomes. New single-cell and spatial omics technologies have revealed the complex architecture of sarcomas with unprecedented resolution. In this review, we use five representative entities – two genomically complex (osteosarcoma, dedifferentiated liposarcoma) and three fusion-driven, genomically “quieter” (Ewing sarcoma, synovial sarcoma, alveolar rhabdomyosarcoma) sarcomas – to showcase recent advances in the field of ITH and the temporal evolution of sarcomas. Specifically, we review how clonal and subclonal molecular alterations, fluctuations in oncogene activity and other forms of cellular plasticity, as well as the formation of complex intratumor ecosystems, drive sarcoma progression and shape therapy resistance. We also provide an overview of recent advances in modeling ITH in sarcomas, as well as in evaluating functional diversity and assessing patient-specific treatment responses. Finally, we outline future directions in ITH research and its clinical implications.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"120 ","pages":"Pages 31-47"},"PeriodicalIF":15.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Energy metabolism, nutrition and cancer","authors":"E. Camajani ,&nbsp;S. Gorini ,&nbsp;A. Feraco ,&nbsp;A. Armani ,&nbsp;M. Caprio","doi":"10.1016/j.semcancer.2026.01.005","DOIUrl":"10.1016/j.semcancer.2026.01.005","url":null,"abstract":"<div><div>Cancer is a complex group of diseases characterized by the uncontrolled growth and spread of abnormal cells, and it remains a major global health concern. In order to meet the increased energy and biosynthetic requirements of rapid growth, cancer cells undergo metabolic reprogramming. In this setting, nutrition exerts a crucial influence on nutrients availability and increasing evidence highlights the significant role of nutrition in the prevention, development, and management of cancer. Dietary patterns and nutrient intake can influence cancer risk through various biological mechanisms, including inflammation, oxidative stress, immune modulation, and hormonal regulation. Diets high in processed foods, red meats, saturated fats and added sugars, have been associated with an increased risk of several cancers. Such diets may contribute to chronic inflammation, insulin resistance, and obesity—conditions known as major risk factors for cancer. Obesity itself is considered a significant contributor to cancer incidence and mortality, linking excess body fat to hormonal imbalances and altered metabolic pathways. Conversely, balanced diets rich in fruits, vegetables, whole grains, legumes, healthy fats and low refined carbohydrates, provide essential vitamins, minerals, fiber, and phytochemicals that have protective properties. These components can help the scavenging of free radicals, reduce DNA damage, and regulate cell growth, potentially lowering the risk of developing certain types of cancer. Nutritional needs in patients with cancer become complex, because of changes in metabolism and tolerance, frequently associated with cancer progression and treatment. Personalized nutritional support can help maintain body weight, preserve muscle mass, and improve treatment tolerance, potentially enhancing overall performance status and survival. While nutrition is not a cure for cancer, it is an essential component of an integrative approach to prevention and care. Further research is necessary to explore how diet can be optimized to support long-term health, reduce recurrence, and improve outcomes in cancer.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"120 ","pages":"Pages 4-15"},"PeriodicalIF":15.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer therapy-related cardiovascular toxicity: Current progress and future perspectives","authors":"Hongcai Shang,&nbsp;William Cho,&nbsp;Yanwei Xing","doi":"10.1016/j.semcancer.2026.01.004","DOIUrl":"10.1016/j.semcancer.2026.01.004","url":null,"abstract":"","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"120 ","pages":"Pages 1-3"},"PeriodicalIF":15.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}