Seminars in cancer biology最新文献

{"title":"Metabolic pathway analysis of tumors using stable isotopes","authors":"Qiufen Bi ,&nbsp;Junzhang Zhao ,&nbsp;Jun Nie ,&nbsp;Fang Huang","doi":"10.1016/j.semcancer.2025.05.002","DOIUrl":"10.1016/j.semcancer.2025.05.002","url":null,"abstract":"<div><div>Metabolic reprogramming is pivotal in malignant transformation and cancer progression. Tumor metabolism is shaped by a complex interplay of both intrinsic and extrinsic factors that are not yet fully elucidated. It is of great value to unravel the complex metabolic activity of tumors in patients. Metabolic flux analysis (MFA) is a versatile technique for investigating tumor metabolism <em>in vivo</em>, it has increasingly been applied to the assessment of metabolic activity in cancer in the past decade. Stable-isotope tracing have shown that human tumors use diverse nutrients to fuel central metabolic pathways, such as the tricarboxylic acid cycle and macromolecule synthesis. Precisely how tumors use different fuels, and the contribution of alternative metabolic pathways in tumor progression, remain areas of intensive investigation. In this review, we systematically summarize the evidence from <em>in vivo</em> stable- isotope tracing in tumors and describe the catabolic and anabolic processes involved in altered tumor metabolism. We also discuss current challenges and future perspectives for MFA of human cancers, which may provide new approaches in diagnosis and treatment of cancer.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"113 ","pages":"Pages 9-24"},"PeriodicalIF":12.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941847","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":"Mechanisms and applications of apolipoproteins and apolipoprotein mimetic peptides: Common pathways in cardiovascular disease and cancer","authors":"Samuel C. Delk ,&nbsp;Faheem W. Gurgis ,&nbsp;Srinivasa T. Reddy","doi":"10.1016/j.semcancer.2025.05.006","DOIUrl":"10.1016/j.semcancer.2025.05.006","url":null,"abstract":"<div><div>Apolipoproteins are the defining functional component of lipoproteins and play critical roles in lipid transport and metabolism. High-density lipoprotein (HDL) and its primary functional constituent, apolipoprotein A-I, are of particular importance because of anti-inflammatory and antioxidant properties. Apolipoprotein mimetic peptides are short-chain amino acids designed to mimic the functions and alpha-helical structure of endogenous apolipoproteins and have demonstrated efficacy in ameliorating animal models of cardiovascular disease (CVD) and cancer. The mechanisms underlying the mimetics are yet to be fully elucidated, but a comprehensive review of the literature suggests that the peptides attack pathways shared in the pathophysiology of both diseases. This review also discusses the many pre-clinical studies on the mimetic peptides, highlighting possible mechanisms at work in each. Proposed mechanisms of protection against CVD and cancer include binding and removal of pro-inflammatory oxidized lipids, reduction in reactive oxygen species, and modulation of immune cell populations. Additionally, nanoparticles (NP) formulations incorporating apolipoprotein mimetic peptides or recombinant apolipoproteins have exhibited anti-atherogenic and anti-cancer activity. To date, clinical trials to assess the effect of reconstituted HDL NPs on CVD outcomes have not shown significant improvement. The large body of successful animal studies on apolipoproteins and apolipoprotein mimetic peptides presents a disconnect between pre-clinical and clinical efficacy, highlighting the need for a more complete understanding of the underlying pathways and mechanisms.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"113 ","pages":"Pages 74-84"},"PeriodicalIF":12.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045926","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 pancreatic cancer screening by identification of pathogenic variants of BRCA2/ BRCA1 in healthy individuals who have no known family history of pancreatic cancer: The arguments for and against.","authors":"Julie Earl ,&nbsp;Agapi Kataki ,&nbsp;Federico Canzian ,&nbsp;Eithne Costello ,&nbsp;Daniele Campa ,&nbsp;William Greenhalf","doi":"10.1016/j.semcancer.2025.05.001","DOIUrl":"10.1016/j.semcancer.2025.05.001","url":null,"abstract":"<div><div>The majority of patients with pancreatic ductal adenocarcinoma (PDAC) are no longer suitable for treatment with curable intent at the time of diagnosis resulting in a 5-year survival of less than 10 %. Imaging of asymptomatic individuals could identify early cancers, but only with a risk of falsely identifying a benign lesion as malignant. Screening of an unselected population would result in far more such false positives than true early cancers. Selection before screening is therefore essential, but there are very few populations at high enough risk to make screening more beneficial than counterproductive. These populations include carriers of specific mutations in <em>BRCA2,</em> and arguably <em>BRCA1,</em> who have a family history of PDAC. These pathogenic mutations all have a predictable effect in making loss of Homologous Recombination Repair (HRR) likely in a carrier’s lifetime. In this review the impact of such loss of HRR function on the likelihood of PDAC development will be discussed. Furthermore, it will be discussed whether the identification of a germline pathogenic mutation is sufficient to justify carrier surveillance for the development of the malignancy, or whether the current practice of screening only those carriers with a close relative diagnosed with PDAC is justifiable, as only a proportion of carriers are at high risk. The review will go beyond this to discuss whether there is an essential need to better define and stratify those at high risk, so that only high-risk carriers are put on surveillance.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"113 ","pages":"Pages 1-8"},"PeriodicalIF":12.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928063","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":"Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers","authors":"Yuki Fujii ,&nbsp;Zahra Asadi ,&nbsp;Kamiya Mehla","doi":"10.1016/j.semcancer.2025.04.001","DOIUrl":"10.1016/j.semcancer.2025.04.001","url":null,"abstract":"<div><div>Cathepsins, a group of lysosomal peptidases, have traditionally been recognized as tumor facilitators. Recent research, however, highlights their critical role in orchestrating cancer and the tumor microenvironment (TME). Primality, cathepsins degrade extracellular matrix, enabling cancer cells to invade and metastasize, while also promoting vascular endothelial infiltration and subsequent angiogenesis. Additionally, cathepsins boost fibroblast growth, thereby supporting tumor progression. More importantly, cathepsins are pivotal in modulating immune cells within the TME by regulating their recruitment, antigen processing and presentation, differentiation, and cell death, primarily contributing to immune suppression. Given their overexpression in tumors and elevated levels in the circulation of cancer patients, it is crucial to consider the systemic effects of cathepsins. Although the comprehensive role of cathepsins in cancer patients’ bodies remains underexplored, they likely influence systemic immunity and inflammation, cellular metabolism, muscle wasting, and distant metastasis through their unique proteolytic functions. Notably, cathepsins also confer resistance to chemoradiotherapy by rewriting the cellular profile within the TME. In this context, promising results are emerging from studies combining cathepsin inhibitors with conventional therapies to suppress tumor development effectively. This review aims to decipher the cathepsin-driven networks within cancer cells and the TME, detailing their contribution to chemoradioresistance by reshaping both micro- and macroenvironments. Furthermore, we explore current and future perspectives on therapies targeting cathepsins’ interactions, offering insights into innovative treatment strategies.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"112 ","pages":"Pages 150-166"},"PeriodicalIF":12.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870470","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":"Vitamin D: What role in obesity-related cancer?","authors":"Pierrick Martinez ,&nbsp;William B. Grant","doi":"10.1016/j.semcancer.2025.03.007","DOIUrl":"10.1016/j.semcancer.2025.03.007","url":null,"abstract":"<div><div>Obesity is an important risk factor for incidence and death for many types of cancer. Vitamin D reduces risk of incidence and death for many types of cancer. This review outlines the mechanisms by which obesity increases risk of cancer, how vitamin D reduces risk of cancer, and the extent to which vitamin D counters the effects of obesity in cancer. Vitamin D is a partial ally against some of obesity's pro-carcinogenic effects, notably by reducing inflammation and regulating sex hormone receptors, leptin resistance, cellular energy metabolism, the microbiome, and hypoxia. However, it can act stronger in against the renin-angiotensin system, insulin resistance, and oxidative stress in cancer. Additionally, excess fat tissue sequesters vitamin D and, along with its dilution in increased body volume, further reduces its bioavailability and serum concentration, limiting its protective effects against cancer. In conclusion, while vitamin D cannot reverse obesity, it plays a significant role in mitigating its pro-carcinogenic effects by targeting several mechanisms.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"112 ","pages":"Pages 135-149"},"PeriodicalIF":12.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799978","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":"Diversity of metabolic features and relevance to clinical subtypes of gliomas","authors":"Pushan Dasgupta,&nbsp;Vinay K. Puduvalli","doi":"10.1016/j.semcancer.2025.03.008","DOIUrl":"10.1016/j.semcancer.2025.03.008","url":null,"abstract":"<div><div>Gliomas carry a dismal prognosis and have proven difficult to treat. Current treatments and efforts to target individual signaling pathways have failed. This is thought to be due to genetic and epigenetic heterogeneity and resistance. Therefore, interest has grown in developing a deeper understanding of the metabolic alterations that represent drivers and dependencies in gliomas. Therapies that target glioma-specific metabolic dependencies overcome the challenges of disease heterogeneity. Here, we present the diverse metabolic features of each current clinical subtype of glioma. We believe that this approach will enable the development of novel strategies to specifically target the various clinical and molecular subtypes of glioma using these metabolic features.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"112 ","pages":"Pages 126-134"},"PeriodicalIF":12.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792343","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":"Pancreatic neuroendocrine neoplasms (pNENs): Genetic and environmental biomarkers for risk of occurrence and prognosis","authors":"Matteo Tacelli ,&nbsp;Manuel Gentiluomo ,&nbsp;Paolo Biamonte ,&nbsp;Justo P. Castano ,&nbsp;Maja Cigrovski Berković ,&nbsp;Mauro Cives ,&nbsp;Sanja Kapitanović ,&nbsp;Ilaria Marinoni ,&nbsp;Sonja Marinovic ,&nbsp;Ilias Nikas ,&nbsp;Lenka Nosáková ,&nbsp;Sergio Pedraza-Arevalo ,&nbsp;Eleonora Pellè ,&nbsp;Aurel Perren ,&nbsp;Jonathan Strosberg ,&nbsp;Daniele Campa ,&nbsp;Gabriele Capurso","doi":"10.1016/j.semcancer.2025.03.005","DOIUrl":"10.1016/j.semcancer.2025.03.005","url":null,"abstract":"<div><div>Pancreatic neuroendocrine neoplasms (pNENs) are rare and heterogeneous tumors arising from neuroendocrine cells, representing approximately 10 % of all Gastro-Entero-Pancreatic neuroendocrine neoplasms. While most pNENs are sporadic, a subset is associated with genetic syndromes such as multiple endocrine neoplasia type 1 (MEN1) or von Hippel-Lindau disease (VHL). pNENs are further classified into functioning and non-functioning tumors, with distinct clinical behaviors, prognoses, and treatment approaches. This review explores genetic and environmental biomarkers that influence the risk, prognosis, and therapeutic responses in pNENs. The epidemiology of pNENs reveals an increasing incidence, primarily due to advancements in imaging techniques. Genetic factors play a pivotal role, with germline mutations in MEN1, VHL, and other genes contributing to familial pNENs. Somatic mutations, including alterations in the mTOR pathway and DNA maintenance genes such as DAXX and ATRX, are critical in sporadic pNENs. These mutations, along with epigenetic dysregulation and transcriptomic alterations, underpin the diverse clinical and molecular phenotypes of pNENs. Emerging evidence suggests that epigenetic changes, including DNA methylation profiles, can stratify pNEN subtypes and predict disease progression. Environmental and lifestyle factors, such as diabetes, smoking, and chronic pancreatitis, have been linked to an increased risk of sporadic pNENs. While the association between these factors and tumor progression is still under investigation, their potential role in influencing therapeutic outcomes warrants further study. Advances in systemic therapies, including somatostatin analogs, mTOR inhibitors, and tyrosine kinase inhibitors, have improved disease management. Biomarkers such as Ki-67, somatostatin receptor expression, and O6-methylguanine-DNA methyltransferase (MGMT) status are being evaluated for their predictive value. Novel approaches, including the use of circulating biomarkers (NETest, circulating tumor cells, and ctDNA) and polygenic risk scores, offer promising avenues for non-invasive diagnosis and monitoring. Despite these advancements, challenges remain, including the need for large, well-annotated datasets and validated biomarkers. Future research should integrate multi-omics approaches and leverage liquid biopsy technologies to refine diagnostic, prognostic, and therapeutic strategies. Interdisciplinary collaborations and global consortia are crucial for overcoming current limitations and translating research findings into clinical practice. These insights hold promise for improving prevention, early detection, and tailored treatments, ultimately enhancing patient outcomes.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"112 ","pages":"Pages 112-125"},"PeriodicalIF":12.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739065","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 reprogramming of tumor microenviroment by engineered bacteria","authors":"Heng Wang,&nbsp;Fang Xu,&nbsp;Chao Wang","doi":"10.1016/j.semcancer.2025.03.003","DOIUrl":"10.1016/j.semcancer.2025.03.003","url":null,"abstract":"<div><div>The tumor microenvironment (TME) is a complex ecosystem that plays a crucial role in tumor progression and response to therapy. The metabolic characteristics of the TME are fundamental to its function, influencing not only cancer cell proliferation and survival but also the behavior of immune cells within the tumor. Metabolic reprogramming—where cancer cells adapt their metabolic pathways to support rapid growth and immune evasion—has emerged as a key factor in cancer immunotherapy. Recently, the potential of engineered bacteria in cancer immunotherapy has gained increasing recognition, offering a novel strategy to modulate TME metabolism and enhance antitumor immunity. This review summarizes the metabolic properties and adaptations of tumor and immune cells within the TME and summarizes the strategies by which engineered bacteria regulate tumor metabolism. We discuss how engineered bacteria can overcome the immunosuppressive TME by reprogramming its metabolism to improve antitumor therapy. Furthermore, we examine the advantages, potential challenges, and future clinical translation of engineered bacteria in reshaping TME metabolism.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"112 ","pages":"Pages 58-70"},"PeriodicalIF":12.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739064","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 relationship of the microbiome, associated metabolites and the gut barrier with pancreatic cancer","authors":"Neil Daniel ,&nbsp;Riccardo Farinella ,&nbsp;Flavia Belluomini ,&nbsp;Almir Fajkic ,&nbsp;Cosmeri Rizzato ,&nbsp;Pavel Souček ,&nbsp;Daniele Campa ,&nbsp;David J. Hughes","doi":"10.1016/j.semcancer.2025.03.002","DOIUrl":"10.1016/j.semcancer.2025.03.002","url":null,"abstract":"<div><div>Pancreatic cancers have high mortality and rising incidence rates which may be related to unhealthy western-type dietary and lifestyle patterns as well as increasing body weights and obesity rates. Recent data also suggest a role for the gut microbiome in the development of pancreatic cancer. Here, we review the experimental and observational evidence for the roles of the oral, gut and intratumoural microbiomes, impaired gut barrier function and exposure to inflammatory compounds as well as metabolic dysfunction as contributors to pancreatic disease with a focus on pancreatic ductal adenocarcinoma (PDAC) initiation and progression. We also highlight some emerging gut microbiome editing techniques currently being investigated in the context of pancreatic disease. Notably, while the gut microbiome is significantly altered in PDAC and its precursor diseases, its utility as a diagnostic and prognostic tool is hindered by a lack of reproducibility and the potential for reverse causality in case-control cohorts. Future research should emphasise longitudinal and mechanistic studies as well as integrating lifestyle exposure and multi-omics data to unravel complex host-microbiome interactions. This will allow for deeper aetiologic and mechanistic insights that can inform treatments and guide public health recommendations.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"112 ","pages":"Pages 43-57"},"PeriodicalIF":12.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From classical approaches to artificial intelligence, old and new tools for PDAC risk stratification and prediction","authors":"Riccardo Farinella ,&nbsp;Alessio Felici ,&nbsp;Giulia Peduzzi ,&nbsp;Sabrina Gloria Giulia Testoni ,&nbsp;Eithne Costello ,&nbsp;Paolo Aretini ,&nbsp;Ricardo Blazquez-Encinas ,&nbsp;Elif Oz ,&nbsp;Aldo Pastore ,&nbsp;Matteo Tacelli ,&nbsp;Burçak Otlu ,&nbsp;Daniele Campa ,&nbsp;Manuel Gentiluomo","doi":"10.1016/j.semcancer.2025.03.004","DOIUrl":"10.1016/j.semcancer.2025.03.004","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is recognized as one of the most lethal malignancies, characterized by late-stage diagnosis and limited therapeutic options. Risk stratification has traditionally been performed using epidemiological studies and genetic analyses, through which key risk factors, including smoking, diabetes, chronic pancreatitis, and inherited predispositions, have been identified. However, the multifactorial nature of PDAC has often been insufficiently addressed by these methods, leading to limited precision in individualized risk assessments. Advances in artificial intelligence (AI) have been proposed as a transformative approach, allowing the integration of diverse datasets—spanning genetic, clinical, lifestyle, and imaging data into dynamic models capable of uncovering novel interactions and risk profiles. In this review, the evolution of PDAC risk stratification is explored, with classical epidemiological frameworks compared to AI-driven methodologies. Genetic insights, including genome-wide association studies and polygenic risk scores, are discussed, alongside AI models such as machine learning, radiomics, and deep learning. Strengths and limitations of these approaches are evaluated, with challenges in clinical translation, such as data scarcity, model interpretability, and external validation, addressed. Finally, future directions are proposed for combining classical and AI-driven methodologies to develop scalable, personalized predictive tools for PDAC, with the goal of improving early detection and patient outcomes.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"112 ","pages":"Pages 71-92"},"PeriodicalIF":12.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}