Seminars in cancer biology最新文献

{"title":"Cancer prevention and interception with antidiabetic and anti-obesity drugs: Current and future perspectives","authors":"Adriana Albini ,&nbsp;Anna Rita Cantelmo ,&nbsp;Lorenzo Mortara ,&nbsp;Douglas M. Noonan ,&nbsp;Giovanni Corso","doi":"10.1016/j.semcancer.2025.07.008","DOIUrl":"10.1016/j.semcancer.2025.07.008","url":null,"abstract":"<div><div>Obesity and type 2 diabetes are major risk factors for cardiovascular diseases and multiple malignancies, and epidemiology reveals an increasing burden of obesity-related cancers, in particular liver, pancreatic and endometrial. Obesity is also clearly associated with an increased risk of breast cancer, particularly in postmenopausal women. Chronic hyperinsulinemia, systemic inflammation, and metabolic dysregulation create a tumor-promoting environment, emphasizing the need for interventions that target metabolic health and can provide cancer prevention or interception. This review examines the potential cancer-preventive effects of antidiabetic and anti-obesity drugs, summarizing current preclinical and clinical evidence on their mechanisms and efficacy. Among these agents, metformin has been extensively studied, demonstrating anticancer properties through AMP-activated protein kinase activation, mammalian target of rapamycin inhibition, and reduced insulin-like growth factor 1 signaling. Glucagon-like peptide-1 receptor agonists, including semaglutide and tirzepatide, promote weight loss, insulin sensitivity, and anti-inflammatory effects, with emerging evidence suggesting direct tumor-suppressive actions. Sodium-glucose cotransporter 2 inhibitors modulate tumor metabolism by reducing glucose availability and mitigating systemic inflammation. Other agents, including dipeptidyl peptidase-4 inhibitors, thiazolidinediones, sulfonylureas, and alpha-glucosidase inhibitors, have shown mixed evidence regarding their potential anticancer effects, necessitating further investigation. While observational studies and meta-analyses suggest a potential reduction in cancer risk with certain antidiabetic and anti-obesity agents, randomized controlled trials specifically assessing cancer prevention are limited. Additionally, long-term safety concerns, including potential tumor-promoting effects in specific contexts, warrant further investigation. Future research should focus on large-scale clinical trials and mechanistic studies to validate the oncologic benefits and risks of these agents.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"115 ","pages":"Pages 40-52"},"PeriodicalIF":15.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699378","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":"The role of deiodinases on metabolic alteration in cancer","authors":"Caterina Miro ,&nbsp;Annunziata Gaetana Cicatiello ,&nbsp;Monica Dentice ,&nbsp;Annarita Nappi","doi":"10.1016/j.semcancer.2025.07.003","DOIUrl":"10.1016/j.semcancer.2025.07.003","url":null,"abstract":"<div><div>Deiodinases are key regulators of Thyroid Hormone (TH) bioavailability, exerting a precise spatial and temporal control over T3 levels in peripheral tissues. By dynamically modulating TH activation and inactivation, deiodinases allow target organs to adapt TH signaling to physiological and pathological demands, highlighting their importance in both health and disease. In cancer, their dysregulated expression reprograms cellular metabolism and shapes the tumor microenvironment (TME). Type 3 deiodinase (D3), frequently upregulated in proliferative and hypoxic tumor regions, fosters cell proliferation and resistance to differentiation. Conversely, type 2 deiodinase (D2) sustains glycolytic metabolism, angiogenesis, and redox disbalance, particularly in aggressive and p53-deficient tumors. Beyond cancer cells, deiodinases activity influences stromal and immune compartments, impacting glutamine metabolism and immune cell plasticity. This complex endocrine-metabolic axis supports tumor adaptation to stress and contributes to the emergence of resistance to therapy. Recent advances reveal the potential of targeting deiodinases to counteract cancer metabolic reprogramming and re-sensitize tumors to treatment. Given the essential and multifaceted roles of deiodinases in cancer biology, a comprehensive understanding of their mechanisms of action, regulation, and clinical implications is critical. This review aims to summarize current knowledge on the roles of deiodinases in cancer metabolism and immunity, focusing on their biochemical properties, regulatory networks, tissue-specific functions, and contributions to disease. In doing so, we seek to highlight emerging concepts in local TH signaling and explore potential avenues for therapeutic intervention targeting deiodinase pathways in precision oncology.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 215-226"},"PeriodicalIF":12.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619968","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":"CRISPR/Cas9 genome engineering in PDAC: From preclinical studies to translation and clinical research","authors":"Yanxi Lu ,&nbsp;Jojanneke Stoof ,&nbsp;Yaba Rosette Tanoé ,&nbsp;Naomi Walsh ,&nbsp;Maarten F. Bijlsma ,&nbsp;Huijun Lei ,&nbsp;Tianhui Chen ,&nbsp;Jelena Grahovac ,&nbsp;Robert Grützmann ,&nbsp;Christian Pilarsky","doi":"10.1016/j.semcancer.2025.07.004","DOIUrl":"10.1016/j.semcancer.2025.07.004","url":null,"abstract":"<div><div>CRISPR/Cas9 technology has emerged as a powerful tool in pancreatic ductal adenocarcinoma cancer (PDAC) research, facilitating the study of genes involved in cell signaling pathways, proliferation, migration, invasion, and chemotherapy resistance. In this review, we discuss the evolution of CRISPR technologies from sophisticated editing techniques to broad screening methods, examine the utility of isogenic models and genetically engineered mouse models (GEMMs). We also explore how CRISPR/Cas9 screens can reveal immune-tumor cell interactions, highlighting the multifaceted role of this technology in PDAC research. Moreover, we emphasize the use of CRISPR technology in diagnostics for CAR-T cell therapies, where CRISPR/Cas9 enhances the precision of targeting malignant cells while minimizing off-tumor effects.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 242-255"},"PeriodicalIF":12.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619967","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":"The impact of sarcopenic obesity on cancer clinical outcomes","authors":"Bahadır Köylü ,&nbsp;Cem Sulu ,&nbsp;Volkan Demirhan Yumuk ,&nbsp;Perran Fulden Yumuk","doi":"10.1016/j.semcancer.2025.07.002","DOIUrl":"10.1016/j.semcancer.2025.07.002","url":null,"abstract":"<div><div>Sarcopenic obesity is a distinct clinical condition characterized by the coexistence of excess fat and reduced muscle mass. Although the prevalence of sarcopenic obesity varies depending on the definition used, it is increasingly recognized as a significant health concern, regardless of age and underlying disease. Despite limited understanding of the crosstalk between sarcopenic obesity and cancer, emerging evidence suggests that sarcopenic obesity not only promotes a metabolic and inflammatory environment conducive to cancer progression but also profoundly impacts treatment efficacy, safety, and survival outcomes. This review provides a concise overview of the key aspects of sarcopenic obesity, with a particular focus on its role in the cancer setting. We also assess existing evidence on its influence on oncological outcomes in both early and advanced stages of the various solid tumor types.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 203-214"},"PeriodicalIF":12.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588547","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":"From awareness to action: Revolutionizing cardio-oncology in China","authors":"Aman Wang,&nbsp;Jiwei Liu","doi":"10.1016/j.semcancer.2025.06.011","DOIUrl":"10.1016/j.semcancer.2025.06.011","url":null,"abstract":"<div><div>Cardio-oncology is an emerging interdisciplinary field focused on the intersection of cancer and cardiovascular disease. With the rising incidence of both cancer and cardiovascular disease in China, establishing a strong cardio-oncology framework has become essential. This review examines the historical development, clinical practices, and key milestones of cardio-oncology in China, emphasizing the importance of multidisciplinary teams, specialized guidelines, and international collaborations. Additionally, it discusses the current challenges and future opportunities for advancing cardio-oncology within China’s healthcare landscape.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 195-202"},"PeriodicalIF":12.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588546","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":"Reopening Pandora’s box: Is there a role for HDL in breast cancer?","authors":"Maria Isabela Bloise Alves Caldas Sawada ,&nbsp;Monique de Fatima de Mello Santana ,&nbsp;Milena Gomes Vancini ,&nbsp;Marisa Passarelli","doi":"10.1016/j.semcancer.2025.07.001","DOIUrl":"10.1016/j.semcancer.2025.07.001","url":null,"abstract":"<div><div>Plasma lipid and lipoprotein profiles are recognized as key modulators in breast cancer (BC) development. Notably, the association between high-density lipoprotein cholesterol (HDLc) and BC remains controversial, with studies reporting positive, negative, or no correlation. This inconsistency may arise from the clinical metrics used to quantify high-density lipoproteins (HDL), such as HDLc and apolipoprotein (apo) A-1, which may not accurately reflect HDL functionality in modulating the tumor microenvironment. Moreover, HDL particles isolated from plasma may undergo modifications influenced by tumor activity, varying with disease stage, severity, and treatment. In this review, we are critically reopening Pandora´s box analyzing evidence on HDLc plasma levels and HDL functionality in BC. Specifically, HDL contributes to tumor regulation by removing excess cellular cholesterol, thereby limiting sterol availability for cell replication and metastasis. Additionally, HDL exerts antioxidant and anti-inflammatory effects and acts as a carrier of bioactive proteins, lipids, and microRNAs, facilitating their delivery to target cells and modulating intracellular signaling and gene expression. Collectively, HDL functionality may serve as a predictor of therapeutic response and clinical outcomes in BC.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 227-241"},"PeriodicalIF":12.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584724","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":"Advances and mechanisms of gut microbiota modulation in enhancing immune checkpoint inhibitor efficacy","authors":"Li Chen ,&nbsp;Baoyi Li ,&nbsp;Menghang Zu ,&nbsp;Rui L. Reis ,&nbsp;Subhas C. Kundu ,&nbsp;Bo Xiao","doi":"10.1016/j.semcancer.2025.06.012","DOIUrl":"10.1016/j.semcancer.2025.06.012","url":null,"abstract":"<div><div>The gut microbiota is crucial for maintaining human health by regulating immune homeostasis and metabolic function. Immune checkpoint inhibitors (ICIs) have emerged as a cornerstone of cancer immunotherapy, yet their effectiveness is often hampered by treatment resistance and immune-related adverse events (irAEs). Increasing evidence highlights gut microbiota as a critical determinant of ICI efficacy. Here, we summarize the advances from preclinical mouse models and clinical trials to systematically illustrate how gut microbiota modulation strategies, such as fecal microbiota transplantation, specific microorganism supplementation, dietary and lifestyle interventions, and prebiotic/postbiotic supplementation, can enhance ICI therapeutic outcomes and mitigate irAEs. Mechanistically, the gut microbiota shape host immune responses, influencing innate, adaptive, and mucosal immunity, as well as immune checkpoint expression, through microbial translocation, microbiota-derived metabolites, and extracellular vesicles. This review elucidates the intricate interplay between gut microbiota and ICI treatment responses, laying a theoretical groundwork for developing personalized microbiota-based strategies to optimize cancer immunotherapy.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 150-172"},"PeriodicalIF":12.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567784","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":"Navigating the weight: The impact of obesity on gastrointestinal cancer surgery and strategies for improved outcomes","authors":"Gerardo Sarno ,&nbsp;Claudia Reytor-González ,&nbsp;Evelyn Frias-Toral ,&nbsp;Martín Campuzano-Donoso ,&nbsp;Christos S. Katsanos ,&nbsp;Daniel Simancas-Racines","doi":"10.1016/j.semcancer.2025.06.010","DOIUrl":"10.1016/j.semcancer.2025.06.010","url":null,"abstract":"<div><div>Obesity significantly affects gastrointestinal cancer surgery outcomes by creating complex challenges throughout the preoperative, intraoperative, and postoperative stages. This narrative review explores the intricate relationship between obesity and GIC surgery, highlighting the dual burden of obesity as a global public health issue and a determinant of surgical complications. The review aims to analyze physiological and technical hurdles, including limited visibility, prolonged operative times, increased perioperative risks, and adverse recovery outcomes associated with obesity. Evidence emphasizes the critical role of excess visceral fat, systemic inflammation, and insulin resistance in elevating surgical risks. Mitigation strategies involve preoperative nutritional optimization, use of advanced surgical technologies such as robotic-assisted and laparoscopic systems, and individualized postoperative care, encompassing early mobilization, tailored pain management, and close monitoring of metabolic parameters. Despite advancements, knowledge gaps remain, particularly regarding sarcopenic obesity and the long-term impact of preoperative dietary interventions. Future research should focus on refining minimally invasive techniques, integrating personalized medicine, and exploring innovative perioperative protocols to address obesity-related risks effectively. By fostering a multidisciplinary approach, this review underscores the necessity for targeted interventions to enhance outcomes and improve the quality of care for patients with obesity undergoing gastrointestinal cancer surgery.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 138-149"},"PeriodicalIF":12.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519235","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":"The microbiome-immune cell interaction network: Advancing tumor immunotherapy","authors":"Wei Liu,&nbsp;Zhou Lan,&nbsp;Zhenzi Lin,&nbsp;Yuyue Zhao,&nbsp;Junxiang Lian,&nbsp;Guangtao Yu","doi":"10.1016/j.semcancer.2025.06.009","DOIUrl":"10.1016/j.semcancer.2025.06.009","url":null,"abstract":"<div><div>Tumor immunotherapy has achieved revolutionary advancements; however, owing to the complex interplay of multiple intrinsic and extrinsic tumor factors, the patient response rate remains suboptimal. Recent research has emphasized the pivotal role of microbiome in tumor progression. Under normal physiological conditions, microbiome enter orally and colonize sites such as the oral and intestinal mucosa, establishing a dynamic microbiome equilibrium that participates in essential physiological processes, including host metabolism and immune regulation. However, in pathological states, including dysbiosis, tumor initiation, or compromised mucosal barrier function, the microbiome can penetrate the mucosal barrier, infiltrate tumor tissues, and engage in intricate direct or indirect interactions with immune cells. These interactions play a pivotal role in reshaping the tumor immune microenvironment and modulating the host's anti-tumor immune response. This review elaborate the regulatory mechanisms involved in direct and indirect interactions between microbiome and immune cells within tumors, and their implications for tumor immunotherapy. We discuss the external factors that impact these interactions and outline the potential use of engineered bacteria in cancer treatment. From the perspective of the interaction network between microbiomes and immune cells, this review elucidates the mechanisms and potential of microbiomes in tumor immunotherapy, offering new insights and potential targets for innovative strategies in tumor prevention and treatment.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 128-137"},"PeriodicalIF":12.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480164","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":"Lipids and lipoproteins in the interstitial tissue fluid regulate the formation of dysfunctional tissue-resident macrophages: Implications for atherogenic, tumorigenic, and obesogenic processes","authors":"Miriam Lee-Rueckert ,&nbsp;Matti Jauhiainen ,&nbsp;Petri T. Kovanen ,&nbsp;Joan Carles Escolà-Gil","doi":"10.1016/j.semcancer.2025.06.008","DOIUrl":"10.1016/j.semcancer.2025.06.008","url":null,"abstract":"<div><div>An inflammatory and lipid-enriched tissue microenvironment is a common characteristic of the extracellular niches of affected tissues in atherosclerosis, cancer, and obesity. These respective interstitial environments appear to be induced by infiltration of plasma lipids and early local recruitment of monocyte-derived macrophages. In the tissue niches, the macrophages display remarkable phenotypic and functional plasticity and exert multifaceted roles in tissue homeostasis. Multiple local signaling events contribute to the phenotypic polarization of the tissue-resident macrophages into M1-like, M2-like, and multiple mixed subpopulations. This study aims to review and compare the roles of lipids and lipoproteins in shaping the inflammatory and lipid-enriched microenvironments of atherosclerotic arterial intima, malignant tumors, and obese adipose tissue, so generating dysfunctional macrophages. Circulating lipoprotein-bound lipids and albumin-bound fatty acids can cross the vascular endothelial barrier and infiltrate the interstitial fluids, resulting in variable levels of plasma-derived lipids, notably low-density lipoproteins (LDL), high-density lipoproteins (HDL), and locally generated small lipid-poor HDL species (preβ-HDL). Whilst LDL particles mainly supply liver-derived cholesterol to the cells of peripheral tissues, HDL particles can promote the reverse transfer of cellular cholesterol into the circulation and ultimately via the liver to the gut for its fecal excretion. Thus, the LDL/HDL ratio in the interstitial fluids can either promote or prevent cholesterol accumulation in the tissue-resident macrophages. Various types of peripheral cells modify interstitial LDL and HDL particles by oxidation, proteolysis, lipolysis, aggregation, or fusion, rendering them dysfunctional. By engulfing excessive amounts of extracellular lipids and modified LDL particles in such lipid-rich microenvironments, macrophages can become dysfunctional, a typical example being the atherosclerotic arterial intima. Similarly, tissue microenvironments characteristic of several malignant tumors and the obese adipose tissue are rich in triglyceride (TG)-rich lipoproteins and free fatty acids, inducing accumulation of TG and glycerophospholipids in the intracellular lipid droplets of macrophages. The lipid-loaded macrophages are currently considered novel markers for diagnosis and selective therapeutic targets not only in the arterial intima but also in malignant tumors and obese adipose tissue. Together, the available data identify potential roles of lipids and lipoproteins present in the interstitial fluids of the atherosclerotic arterial intima, malignant tumors, and obese adipose tissue in the generation of distinct lipid-loaded macrophage subpopulations and suggest their contributory roles in the development and progression of atherosclerosis, cancer, and obesity, the three major health concerns worldwide.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 104-127"},"PeriodicalIF":12.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369211","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}