Seminars in cancer biology最新文献

{"title":"The biology and evolution of Richter transformation in chronic lymphocytic leukemia","authors":"Ferran Nadeu ,&nbsp;Dimitar G. Efremov","doi":"10.1016/j.semcancer.2026.02.002","DOIUrl":"10.1016/j.semcancer.2026.02.002","url":null,"abstract":"<div><div>Richter transformation (RT) is a relatively rare but clinically challenging event in the natural history of chronic lymphocytic leukemia (CLL), characterized by the abrupt transformation of CLL into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). RT is diagnosed through histopathological confirmation, often prompted by clinical signs such as rapid lymph node enlargement, B symptoms, and elevated metabolic activity on PET-CT. Its incidence ranges from 2 % to 10 % over the CLL course, with higher risk in patients harboring specific high-risk (immuno)genetic features. Clonal relationship to the original CLL clone is crucial to understand the biology of the disease and may guide treatment decisions and anticipate RT evolution. Biologically, RT is driven by genomic instability, loss of cell cycle control, MYC activation, NOTCH alterations, and immune evasion mechanisms, including PD-1/PD-L1 upregulation. Transformation timing varies, occurring either early or late in the CLL course, may be preceded by a phase of accelerated disease, and their seeds may be traced back years before their clinical manifestation. Preclinical models, including genetically engineered mice and patient-derived xenografts, have been instrumental in elucidating the molecular underpinnings of RT, assess its interactions with the tumor microenvironment –including through the B-cell receptor–, and offer platforms for testing novel therapeutic strategies. In this review, we will deepen into the biology and evolution of DLBCL-type RT, revisiting recent publications and discussing new avenues for research in this paradigmatic evolution of CLL.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"120 ","pages":"Pages 48-60"},"PeriodicalIF":15.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202585","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":"Lipid metabolic alterations in cancer: Common pathophysiology with cardiovascular disease","authors":"Maria Llena-Meler ,&nbsp;Alberto Canfran-Duque ,&nbsp;Julio Madrigal-Matute ,&nbsp;Noemi Rotllan","doi":"10.1016/j.semcancer.2026.01.003","DOIUrl":"10.1016/j.semcancer.2026.01.003","url":null,"abstract":"<div><div>Obesity-induced chronic inflammation and lipid metabolic imbalance form a pivotal nexus linking cardiovascular disease and cancer. Dysfunctional adipose tissue establishes a pro-inflammatory environment through hypoxia-driven macrophage polarization, oxidative stress, aberrant lipid signaling, and endocrine crosstalk, mechanisms that collectively foster atherogenesis and tumor promotion. Yet, a comprehensive integration of metabolic and immunological dynamics at the molecular level remains elusive. In this review, we synthesize emerging evidence that metabolic stressors, particularly excessive intake of oxidized and omega-6-enriched lipids, activate NF-κB and NLRP3-dependent inflammatory pathways in macrophages, thereby fostering a pro-tumorigenic and pro-atherogenic microenvironment. We underscore the emerging role of microRNAs as functional mediators connecting lipid metabolism, inflammation, and cellular plasticity across atherosclerotic and neoplastic tissues. These non-coding RNAs modulate key signaling pathways, including the critical PI3K/Akt, NFκB, and TGFβ axes, thereby promoting macrophage phenotype shifts, endothelial dysfunction, aberrant proliferation, and immune evasion. Importantly, interventions aimed at restoring lipid homeostasis, including Mediterranean-style diets, caloric restriction, and regular physical activity, act as important regulators of systemic and tissue-specific inflammation. Nutritional interventions increase monounsaturated and omega-3 fatty acid content and limit oxidized lipid exposure. We propose that combining metabolic modulation with RNA-based therapies, such as miRNA mimics or inhibitors delivered through nanoparticles or pH-responsive peptide systems, may offer synergistic avenues for controlling metabolic inflammation in both cancer and cardiovascular disease. Future research should focus on the targeted and context-dependent regulation of non-coding RNA networks within immuno-metabolic circuits, advancing precision medicine in cardio-oncology.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"119 ","pages":"Pages 83-105"},"PeriodicalIF":15.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952961","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":"Lipid dysregulation in renal cancer: Drivers of tumor growth and determinants of treatment-induced toxicity","authors":"Mohammed Alnukhali ,&nbsp;Alessia Fornoni ,&nbsp;Alan Pollack ,&nbsp;Anis Ahmad","doi":"10.1016/j.semcancer.2025.12.010","DOIUrl":"10.1016/j.semcancer.2025.12.010","url":null,"abstract":"<div><h3>Background</h3><div>Clear cell renal cell carcinoma (ccRCC) exhibits a distinctive metabolic signature marked by the excessive buildup of cholesterol and neutral lipids. This phenotype stems largely from the loss of the von Hippel–Lindau (VHL) tumor suppressor and the resulting stabilization of hypoxia-inducible factors (HIFs). The altered lipid environment enables ccRCC cells to sustain growth, evade immune surveillance, and withstand contemporary systemic therapies. Increasing evidence indicates that similar disturbances in lipid metabolism contribute to kidney injury during cancer treatment, suggesting that dysregulated cholesterol handling represents a shared pathologic foundation linking tumor progression with therapy-induced nephrotoxicity.</div></div><div><h3>Scope of review</h3><div>This review brings together mechanistic, preclinical, and translational findings that illuminate how defective cholesterol regulation—particularly diminished ABCA1-mediated efflux promotes tumor aggressiveness while heightening renal vulnerability to radiation therapy, tyrosine kinase inhibitors (TKIs), and immune checkpoint inhibitors (ICIs). We examine lipid droplet dynamics, cholesteryl ester biology, and mitochondrial perturbations in ccRCC cells and renal parenchymal cells exposed to therapeutic stress.</div></div><div><h3>Major conclusions</h3><div>Across ccRCC therapies, lipid accumulation drives renal injury, with lipid-sensitive cells, particularly podocytes, undergoing cytoskeletal and slit-diaphragm disruption, proteinuria, and progressive glomerular damage in response to cholesterol overload, oxidative stress, and inflammatory signaling. Within the tumor, suppression of ABCA1 perpetuates lipid droplet expansion, reinforces resistance to therapy, and intensifies metabolic strain within the microenvironment.</div></div><div><h3>Future directions</h3><div>Restoring cholesterol balance through LXR agonists, cyclodextrins, or strategies that enhance ABCA1 function holds promise for limiting renal toxicity while simultaneously impairing tumor survival mechanisms. Advances in lipidomics, metabolic imaging, and biomarker-driven stratification may facilitate precision approaches that integrate metabolic correction with effective oncologic care.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"119 ","pages":"Pages 54-64"},"PeriodicalIF":15.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145945838","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":"Integrative spatial omics and artificial intelligence: transforming cancer research with omics data and AI","authors":"Maddison McKenzie ,&nbsp;Sergio Erdel Irac ,&nbsp;Zhian Chen ,&nbsp;Afshin Moradi ,&nbsp;Adrianne Jenner ,&nbsp;Quan Nguyen ,&nbsp;Behnam Rashidieh","doi":"10.1016/j.semcancer.2026.01.002","DOIUrl":"10.1016/j.semcancer.2026.01.002","url":null,"abstract":"<div><div>The integration of multi-omics data, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics, coupled with histological spatial data has transformed biomedical research, offering unprecedented insights into cellular functions and disease mechanisms. However, the sheer volume and complexity of these datasets present a significant challenge in terms of interpretation and clinical translation. Artificial intelligence (AI) and machine learning (ML) are transforming data analysis, enabling the extraction of meaningful patterns from high-dimensional datasets and facilitating the development of predictive models. This shift is particularly transformative in cancer research, where understanding the tumor microenvironment (TME) and its spatial dynamics is crucial for improving therapeutic outcomes. This review explores recent advancements in spatial omics (SO) including spatial transcriptomics (ST) and spatial proteomics (SP), and AI-driven computational models, focusing on their applications in oncology. We discuss key methodologies, including spatial barcoding, in situ sequencing, and digital spatial profiling, and highlight major platforms. AI-powered tools, including deep learning models and spatial graph-based analyses, enhance data interpretation, allowing for robust predictive modeling, biomarker discovery, and personalized therapeutic strategies. Despite their transformative potential, ST and AI-driven approaches face challenges, including high-dimensional data complexity, computational constraints, and standardization of analytical pipelines. Addressing these challenges requires advanced mathematical frameworks such as spatial graph theory, topological data analysis, and agent-based modeling, which refine data integration and improve biological insights. Future research should focus on enhancing spatial resolution, cross-platform data harmonization, and AI-driven predictive models to advance precision oncology. By integrating ST, SP, and AI, researchers can develop dynamic, patient-specific treatment strategies, ultimately improving clinical outcomes and deepening our understanding of cancer progression and immune system interactions.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"119 ","pages":"Pages 65-82"},"PeriodicalIF":15.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952987","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":"Heartbreakers and healers: RNA rebels in cardio-oncology","authors":"Celestina Agyemang-Dua ,&nbsp;Charles S. Chung ,&nbsp;Cristina Espinosa-Diez","doi":"10.1016/j.semcancer.2025.12.008","DOIUrl":"10.1016/j.semcancer.2025.12.008","url":null,"abstract":"<div><div>Cancer therapies save lives but often “break hearts” by damaging the cardiovascular system. As survival improves, therapy-induced cardiotoxicity has become a defining challenge of modern oncology. Recent discoveries reveal that long non-coding RNAs (lncRNAs), once dismissed as genomic noise, are the “RNA rebels” orchestrating cellular responses to cancer treatments. These molecules act as both heartbreakers and healers, amplifying or counteracting oxidative stress, mitochondrial dysfunction, apoptosis, and vascular injury. In anthracycline, radiation, and VEGF-targeted therapies, lncRNAs govern key processes that dictate whether cells succumb to damage or mount protective repair responses. Pro-injury lncRNAs exacerbate senescence and inflammation, while protective ones preserve mitochondrial homeostasis and limit cell death. Beyond mechanistic insight, these molecules hold clinical promise as biomarkers and therapeutic targets, guiding RNA-based strategies to predict, prevent, and treat cardiotoxicity. Understanding how they blur the line between protection and harm may redefine how we safeguard the heart in the era of precision cardio oncology.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"119 ","pages":"Pages 1-11"},"PeriodicalIF":15.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834629","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":"Microbiome-modulated immunotherapy in oncology: Current applications and future prospects","authors":"Yu Liu ,&nbsp;Keyan Miao ,&nbsp;Xi Yang","doi":"10.1016/j.semcancer.2026.01.001","DOIUrl":"10.1016/j.semcancer.2026.01.001","url":null,"abstract":"<div><div>Cancer immunotherapy has transformed oncology, yet therapeutic efficacy remains heterogeneous and frequently limited by primary or acquired resistance. Increasing evidence demonstrates that both intra- and extratumoral microbiota critically modulate antitumor immunity, influencing clinical responses of immunotherapy and immune-related adverse events (irAEs). Microbial communities regulate the tumor immune microenvironment through multiple mechanisms, including microbe-associated molecular patterns, microbial metabolites, and outer membrane vesicles, acting on tumor or immune cells. These insights have fostered the development of microbiome-based applications in oncology, ranging from predictive biomarkers to therapeutic interventions such as engineered bacteria, fecal microbiota transplantation, probiotics, prebiotics, outer membrane vesicles, bacteriophages, and dietary modulation. Early-phase clinical studies indicate that microbiota-targeted strategies can enhance immunotherapy efficacy or mitigate irAEs, although strain specificity, interindividual variability, and safety remain significant challenges. Future progress will require mechanistic elucidation, integration of multi-omics analyses, standardization of methodologies, and personalized intervention frameworks to translate microbiome modulation into clinically actionable, precision immunotherapy.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"119 ","pages":"Pages 38-53"},"PeriodicalIF":15.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952935","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":"Immune checkpoint inhibitor-induced myocarditis: focus on the downstream pathogenic components and potential therapeutics","authors":"Yifan Chen ,&nbsp;Xuejun Wang ,&nbsp;Yihui Shen ,&nbsp;Hui Zhang ,&nbsp;Cheng Yu ,&nbsp;Leilei Cheng ,&nbsp;Junbo Ge","doi":"10.1016/j.semcancer.2025.12.004","DOIUrl":"10.1016/j.semcancer.2025.12.004","url":null,"abstract":"<div><div>Advent of immune checkpoint inhibitors (ICIs) has renovated onco-immunotherapy, with around 50 % of cancer patients suitable for the treatment. However, patients treated by ICIs are in jeopardy for immune-related adverse events (irAEs) that attack any organ including the heart. ICIs-induced myocarditis (ICIIM) is an uncommon but possibly fatal irAE. With the increasing use of ICIs and improved diagnosis of this disease, the incidence of ICIIM is growing rapidly. In this review, we briefly overview roles of T cells and their immune checkpoints, and categorize the pathogenic process of ICIIM into three stages (upstream, midstream and downstream), with addressing recent research progress on the pathogenic mechanisms in each stage, particularly focusing on the downstream core pathogenic components and potential therapeutics for this disease.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"119 ","pages":"Pages 12-23"},"PeriodicalIF":15.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800820","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":"Spatial multi-omics in precision medicine: Integrating biological insights through multidisciplinary collaboration","authors":"Da Yeon Kim ,&nbsp;Jeeyong Lee ,&nbsp;Jiwon Choi ,&nbsp;Hayeon Shin ,&nbsp;Jason S. Lee ,&nbsp;Eun Ju Kim","doi":"10.1016/j.semcancer.2025.12.009","DOIUrl":"10.1016/j.semcancer.2025.12.009","url":null,"abstract":"<div><div>Spatial multi-omics has emerged as a transformative approach in biomedical research, enabling the integration of diverse molecular modalities while preserving their native spatial contexts. This review provides an overview of spatial multi-omics technologies, focusing on data acquisition, quality management, and integration strategies across transcriptomic, genomic, epigenomic, proteomic, and metabolomic layers. Spatial transcriptomics is highlighted as a foundational framework for aligning multi-omics data with histological and cellular architecture. We emphasize its applications in elucidating tumor heterogeneity, immune–stromal interactions, and metabolic or epigenetic dynamics within the tumor microenvironment, which are crucial for understanding disease progression and therapeutic response. The review further discusses key challenges such as technical noise, batch effects, and the complexity of high-dimensional data integration, along with optimization strategies for sampling and analysis in both clinical and research settings. Ethical and regulatory considerations, including patient data privacy and responsible implementation of artificial intelligence, are also examined in the context of clinical translation. Taken together, this review offers an integrative synthesis of spatial multi-omics technologies and their applications in cancer biology, providing a balanced perspective to help researchers and clinicians navigate this rapidly evolving field and recognize its translational potential for advancing precision medicine.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"119 ","pages":"Pages 24-37"},"PeriodicalIF":15.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879021","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":"Targeting aging-related signaling pathways for cancer therapy","authors":"Hiroyuki Inuzuka,&nbsp;Wenyi Wei","doi":"10.1016/j.semcancer.2025.12.007","DOIUrl":"10.1016/j.semcancer.2025.12.007","url":null,"abstract":"","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"118 ","pages":"Pages 87-89"},"PeriodicalIF":15.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834672","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":"Microbiota and cancer immunotherapy: Mechanisms, clinical implications, and precision therapeutics","authors":"Dongliang Wei ,&nbsp;Yilan Sun ,&nbsp;Jing Han ,&nbsp;Jiannan Liu","doi":"10.1016/j.semcancer.2025.12.002","DOIUrl":"10.1016/j.semcancer.2025.12.002","url":null,"abstract":"<div><div>The microbiota has emerged as a pivotal modulator of cancer immunotherapy, offering novel insights into the efficacy and toxicity of immune checkpoint inhibitors (ICIs). Recent evidence highlights that microbial communities and their metabolites dynamically regulate host immunity by priming dendritic cells, enhancing T-cell infiltration, and reprogramming the tumor microenvironment. Microbiome dysbiosis is implicated in immune-related adverse events (irAEs), underscoring its dual role in therapeutic outcomes. Leveraging these findings, precision microbiome interventions, including fecal microbiota transplantation, engineered probiotics, and dietary modulation, which demonstrate potential to enhance ICIs responsiveness and mitigate irAEs in preclinical and early-phase clinical studies. However, translating these strategies into clinical practice requires rigorous validation through multicenter trials to establish safety, efficacy, and standardized protocols. This review synthesizes current knowledge on the microbiome-immune-oncology axis, with a focus on mechanistic underpinnings, translational challenges, and innovative therapeutic strategies. By integrating microbiome profiling with patient-specific factors, proposing a roadmap for personalized immunotherapy, aligning with the emerging paradigm of precision oncology.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"118 ","pages":"Pages 62-73"},"PeriodicalIF":15.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696265","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}