Seminars in cancer biology最新文献

{"title":"Role of ubiquitination-driven metabolisms in oncogenesis and cancer therapy","authors":"Dongqin Yang ,&nbsp;Can Yang ,&nbsp;Linlin Huang ,&nbsp;Ming Guan ,&nbsp;Chunhua Song","doi":"10.1016/j.semcancer.2025.02.004","DOIUrl":"10.1016/j.semcancer.2025.02.004","url":null,"abstract":"<div><div>Ubiquitination represents one of the most critical post-translational modifications, comprising a multi-stage enzyme process that plays a pivotal role in a myriad of cellular biological activities. The deregulation of the processes of ubiquitination and deubiquitination is associated with the development of cancers and other diseases. This typescript reviews the impact of ubiquitination on metabolic processes, elucidating the regulatory functions of ubiquitination on pivotal enzymes within metabolic pathways in pathological contexts. It underscores the role of ubiquitination-driven metabolism disorders in the etiology of cancers, and oncogenesis, and highlights the potential therapeutic efficacy of targeting ubiquitination-driven enzymes in cancer metabolism, their combination with immune checkpoint inhibitors, and their clinical applications.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"110 ","pages":"Pages 17-35"},"PeriodicalIF":12.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391681","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":"Reshaping the immune microenvironment and reversing immunosenescence by natural products: Prospects for immunotherapy in gastric cancer","authors":"Zhipeng Cao ,&nbsp;Zhilin Wang ,&nbsp;Li Yang ,&nbsp;Tian Li ,&nbsp;Xueshu Tao ,&nbsp;Xing Niu","doi":"10.1016/j.semcancer.2025.02.002","DOIUrl":"10.1016/j.semcancer.2025.02.002","url":null,"abstract":"<div><div>Gastric cancer (GC) represents a global health-care challenge. Recent progress in immunotherapy has elicited attracted considerable attention as a viable treatment option through modulating the host immune system and unleashing pre-existing immunity, which has profoundly revolutionized oncology, especially GC. Nonetheless, low clinical response and intrinsic and acquired resistance remain persistently challenging. The microenvironment of GC comprising multifarious stromal cell types has remarkable immunosuppressive elements that may impact the efficacy of immunotherapy. Immunosenescence is increasingly regarded as a factor that contributes to cancer development, remodels the tumor microenvironment and affects the efficacy of immunotherapy. Natural products are at the forefront of traditional medicine. Senotherapeutics is a class of drugs and natural products capable of delaying, preventing, or reversing the senescence process (i.e., senolytics) or suppressing senescence-associated secretory phenotype (i.e., senomorphics). Emerging evidence supports that natural products can improve the efficacy of existing immunotherapy and expand their indications in GC mainly based upon remodeling the immunosuppressive microenvironment and reversing immunosenescence. The review provides an integrated review of previously reported and ongoing clinical trials with immunotherapeutic regimens in GC and discusses current challenges. Next, we focus on natural compounds that exert anti-GC functions and possess immunomodulatory properties. More attention is paid to the potential of these natural compounds in modulating the immune microenvironment and immunosenescence. Lastly, we discuss the nanomedicine that can overcome the deficiencies of natural products. Altogether, our review suggests the enormous potential of natural compounds in GC immunotherapy, and provides an important direction for future research.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"110 ","pages":"Pages 1-16"},"PeriodicalIF":12.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383221","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 strategies of immunosenescence effects on non-small cell lung cancer (NSCLC) treatment: A comprehensive analysis and future directions","authors":"Huatao Zhou ,&nbsp;Zilong Zheng ,&nbsp;Chengming Fan ,&nbsp;Zijing Zhou","doi":"10.1016/j.semcancer.2025.01.001","DOIUrl":"10.1016/j.semcancer.2025.01.001","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer, remains a leading cause of cancer-related mortality worldwide, particularly among elderly individuals. The phenomenon of immunosenescence, characterized by the progressive decline in immune cell functionality with aging, plays a pivotal role in NSCLC progression and contributes to the diminished efficacy of therapeutic interventions in older patients. Immunosenescence manifests through impaired immune surveillance, reduced cytotoxic responses, and increased chronic inflammation, collectively fostering a pro-tumorigenic microenvironment. This review provides a comprehensive analysis of the molecular, cellular, and genetic mechanisms of immunosenescence and its impact on immune surveillance and the tumor microenvironment (TME) in NSCLC. We explore how aging affects various immune cells, including T cells, B cells, NK cells, and macrophages, and how these changes compromise the immune system’s ability to detect and eliminate tumor cells. Furthermore, we address the challenges posed by immunosenescence to current therapeutic strategies, particularly immunotherapy, which faces significant hurdles in elderly patients due to immune dysfunction. The review highlights emerging technologies, such as single-cell sequencing and CRISPR-Cas9, which offer new insights into immunosenescence and its potential as a therapeutic target. Finally, we outline future research directions, including strategies for rejuvenating the aging immune system and optimizing immunotherapy for older NSCLC patients, with the goal of improving treatment efficacy and survival outcomes. These efforts hold promise for the development of more effective, personalized therapies for elderly patients with NSCLC.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"109 ","pages":"Pages 44-66"},"PeriodicalIF":12.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966448","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":"Multi-omic markers of intraductal papillary mucinous neoplasms progression into pancreatic cancer","authors":"Chiara Corradi ,&nbsp;Manuel Gentiluomo ,&nbsp;Volkan Adsay ,&nbsp;Juan Sainz ,&nbsp;Paolo Riccardo Camisa ,&nbsp;Barbara Wlodarczyk ,&nbsp;Stefano Crippa ,&nbsp;Francesca Tavano ,&nbsp;Gabriele Capurso ,&nbsp;Daniele Campa","doi":"10.1016/j.semcancer.2024.12.005","DOIUrl":"10.1016/j.semcancer.2024.12.005","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is the most lethal and common form of pancreatic cancer, it has no specific symptoms, and most of the patients are diagnosed when the disease is already at an advanced stage. Chemotherapy typically has only a modest effect, making surgery the most effective treatment option. However, only a small percentage of patients are amenable to surgery. One viable strategy to reduce PDAC death burden associated with the disease is to focus on precursor lesions and identify markers able to predict who will evolve into PDAC. While most PDACs are believed to be preceded by pancreatic intraepithelial neoplasms (PanINs), 5–10 % arise from Intraductal papillary mucinous neoplasms (IPMNs), which are mass-forming cystic lesions that are very common in the general population. IPMNs offer an invaluable model of pancreatic carcinogenesis for researchers to analyse, as well as a target population for PDAC early detection by clinicians. The evolution of IPMN into cancer is a complex and multistep process, therefore the identification of individual markers will not be the solution. In recent years, multiple omics technologies have been instrumental to identify possible biomarkers of IPMN progression and carcinogenesis. The only foreseeable strategy will be to integrate multi-omics data, alongside clinical and morphological features, into a progression score or signature using either standard epidemiologic tools or artificial intelligence. The aim of this manuscript is to review the current knowledge on genetic biomarkers and to briefly mention also additional omics, such as metabolomics, the exposome, the miRNome and epigenomics of IPMNs.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"109 ","pages":"Pages 25-43"},"PeriodicalIF":12.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903348","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":"RB functions as a key regulator of senescence and tumor suppression","authors":"Minling Gao ,&nbsp;Haiou Li ,&nbsp;Jinfang Zhang","doi":"10.1016/j.semcancer.2024.11.004","DOIUrl":"10.1016/j.semcancer.2024.11.004","url":null,"abstract":"<div><div>The Retinoblastoma (RB) protein is crucial for regulating gene transcription and chromatin remodeling, impacting cell cycle progression, cellular senescence, and tumorigenesis. Cellular senescence, characterized by irreversible growth arrest and phenotypic alterations, serves as a vital barrier against tumor progression and age-related diseases. RB is crucial in mediating senescence and tumor suppression by modulating the RB-E2F pathway and cross talking with other key senescence effectors such as p53 and p16^INK4a. The interplay between RB-mediated cell cycle arrest and cellular senescence offers critical insights into tumorigenesis and potential therapeutic strategies. Leveraging RB-mediated senescence presents promising opportunities for cancer therapy, including novel approaches in tumor immunotherapy designed to enhance treatment efficacy. This review highlights recent advancements in the RB signaling pathway, focusing on its roles in cellular senescence and tumor suppression, and discusses its potential to improve tumor management and clinical outcomes.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"109 ","pages":"Pages 1-7"},"PeriodicalIF":12.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829721","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":"Mathematical models of intercellular signaling in breast cancer","authors":"Frederick R. Adler ,&nbsp;Jason I. Griffiths","doi":"10.1016/j.semcancer.2025.01.005","DOIUrl":"10.1016/j.semcancer.2025.01.005","url":null,"abstract":"<div><h3>Background and objectives</h3><div>The development and regulation of healthy and cancerous breast tissue is guided by communication between cells. Diverse signals are exchanged between cancer cells and non-cancerous cells of the tumor microenvironment (TME), influencing all stages of tumor progression. Mathematical models are essential for understanding how this complex network determines cancer progression and the effectiveness of treatment.</div></div><div><h3>Methodology</h3><div>We reviewed the current dynamical mathematical models of intercellular signaling in breast cancer, examining models with cancer cells only, fibroblasts, endothelial cells, macrophages and the immune system as whole. We categorized the goals and complexity of these models, to highlight how they can explain many features of cancer emergence and progression.</div></div><div><h3>Results</h3><div>We found that dynamical models of intercellular signaling can elucidate tissue-level dysregulation in cancer by explaining: i) maintenance of non-heritable intratumor phenotypic heterogeneity, ii) transitions between tumor dormancy and accelerated invasive growth, iii) stromal support of tumor vascularization and growth factor enrichment and iv) suppression of immune infiltration and cancer surveillance. These models also provide a framework to propose novel TME-targeting treatment strategies. However, most models were focused on a highly selected and small set of signaling interactions between a few cell types, and their translational applicability were severely limited by the availability of tumor-specific data for personalized model calibration.</div></div><div><h3>Conclusions and implications</h3><div>Mathematical models of breast cancer have many challenges and opportunities to incorporate signaling. The four key challenges are: 1) finding ways to treat signaling networks as a context-dependent language that incorporates non-linear and non-additive responses, 2) identifying the key cell phenotypes that signals control and understanding the feedbacks between signals and phenotype that determine the progression of cancer, (3) estimating parameters of specific patient tumors early in treatment, 4) linking models with novel data collection methods that have single cell and spatial resolution. As our approaches advance, it is our hope that dynamical mathematical models of inter-cellular signaling can play a central role in identifying and testing new treatment strategies as well as forecasting impacts of disease treatment.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"109 ","pages":"Pages 91-100"},"PeriodicalIF":12.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075147","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":"Leveraging epigenetic alterations in pancreatic ductal adenocarcinoma for clinical applications","authors":"Jorg Tost ,&nbsp;Secil Ak-Aksoy ,&nbsp;Daniele Campa ,&nbsp;Chiara Corradi ,&nbsp;Riccardo Farinella ,&nbsp;Alejandro Ibáñez-Costa ,&nbsp;Juan Dubrot ,&nbsp;Julie Earl ,&nbsp;Emma Barreto Melian ,&nbsp;Agapi Kataki ,&nbsp;Georgina Kolnikova ,&nbsp;Gjorgji Madjarov ,&nbsp;Marija Chaushevska ,&nbsp;Jan Strnadel ,&nbsp;Miljana Tanić ,&nbsp;Miroslav Tomas ,&nbsp;Peter Dubovan ,&nbsp;Maria Urbanova ,&nbsp;Verona Buocikova ,&nbsp;Bozena Smolkova","doi":"10.1016/j.semcancer.2025.01.003","DOIUrl":"10.1016/j.semcancer.2025.01.003","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alterations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease. Specific modifications in DNA methylation, histone marks, and non-coding RNAs are emerging as robust predictors of disease progression and patient survival, offering the potential for more precise prognostic tools compared to conventional clinical staging. Moreover, the detection of epigenetic alterations in blood and other non-invasive samples holds promise for earlier diagnosis and improved management of PDAC. This review comprehensively summarises current epigenetic research in PDAC and identifies persisting challenges. These include the complex nature of epigenetic profiles, tumour heterogeneity, limited access to early-stage samples, and the need for highly sensitive liquid biopsy technologies. Addressing these challenges requires the standardisation of methodologies, integration of multi-omics data, and leveraging advanced computational tools such as machine learning and artificial intelligence. While resource-intensive, these efforts are essential for unravelling the functional consequences of epigenetic changes and translating this knowledge into clinical applications. By overcoming these hurdles, epigenetic research has the potential to revolutionise the management of PDAC and improve patient outcomes.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"109 ","pages":"Pages 101-124"},"PeriodicalIF":12.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041561","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":"Cancer cell populations","authors":"Frederick R. Adler,&nbsp;Herbert Levine,&nbsp;Amy Brock","doi":"10.1016/j.semcancer.2024.12.004","DOIUrl":"10.1016/j.semcancer.2024.12.004","url":null,"abstract":"","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"109 ","pages":"Pages 8-9"},"PeriodicalIF":12.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877897","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":"Organoids, tissue slices and organotypic cultures: Advancing our understanding of pancreatic ductal adenocarcinoma through in vitro and ex vivo models","authors":"Secil Ak Aksoy ,&nbsp;Julie Earl ,&nbsp;Jelena Grahovac ,&nbsp;Didem Karakas ,&nbsp;Giulia Lencioni ,&nbsp;Sıla Sığırlı ,&nbsp;Maarten F. Bijlsma","doi":"10.1016/j.semcancer.2024.12.003","DOIUrl":"10.1016/j.semcancer.2024.12.003","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses of all common solid cancers. For the large majority of PDAC patients, only systemic therapies with very limited efficacy are indicated. In addition, immunotherapies have not brought the advances seen in other cancer types. Several key characteristics of PDAC contribute to poor treatment outcomes, and in this review, we will discuss how these characteristics are best captured in currently available <em>ex vivo</em> or <em>in vitro</em> model systems. For instance, PDAC is hallmarked by a highly desmoplastic and immune-suppressed tumor microenvironment that impacts disease progression and therapy resistance. Also, large differences in tumor biology exist between and within tumors, complicating treatment decisions. Furthermore, PDAC has a very high propensity for locally invasive and metastatic growth. The use of animal models is often not desirable or feasible and several <em>in vitro</em> and <em>ex vivo</em> model systems have been developed, such as organotypic cocultures and tissue slices, among others. However, the absence of a full host organism impacts the ability of these models to accurately capture the characteristics that contribute to poor outcomes in PDAC. We will discuss the caveats and advantages of these model systems in the context of PDAC’s key characteristics and provide recommendations on model choice and the possibilities for optimization. These considerations should be of use to researchers aiming to study PDAC in the <em>in vitro</em> setting.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"109 ","pages":"Pages 10-24"},"PeriodicalIF":12.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897219","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":"Fungi, immunosenescence and cancer","authors":"Bin Xu ,&nbsp;Zan Luo ,&nbsp;Xing Niu ,&nbsp;Zhi Li ,&nbsp;Yeping Lu ,&nbsp;Junyu Li","doi":"10.1016/j.semcancer.2025.01.002","DOIUrl":"10.1016/j.semcancer.2025.01.002","url":null,"abstract":"<div><div>Fungal microbes are a small but immunoreactive component of the human microbiome, which may influence cancer development, progression and therapeutic response. Immunosenescence is a process of immune dysfunction that occurs with aging, including lymphoid organ remodeling, contributing to alterations in the immune system in the elderly, which plays a critical role in many aspects of cancer. There is evidence for the interactions between fungi and immunosenescence in potentially regulating cancer progression and remodeling the tumor microenvironment (TME). In this review, we summarize potential roles of commensal and pathogenic fungi in modulating cancer-associated processes and provide more-detailed discussions on the mechanisms of which fungi affect tumor biology, including local and distant regulation of the TME, modulating antitumor immune responses and interactions with neighboring bacterial commensals. We also delineate the features of immunosenescence and its influence on cancer development and treatment, and highlight the interactions between fungi and immunosenescence in cancer. We discuss the prospects and challenges for harnessing fungi and immunosenescence in cancer diagnosis and/or treatment. Considering the limited understanding and techniques in conducting such research, we also provide our view on how to overcome challenges faced by the exploration of fungi, immunosenescence and their interactions on tumor biology.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"109 ","pages":"Pages 67-82"},"PeriodicalIF":12.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954295","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}