Seminars in cancer biology最新文献

{"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}

{"title":"The dual function of autophagy in doxorubicin-induced cardiotoxicity: Mechanism and natural products","authors":"Nannan Tan ,&nbsp;Hanwen Luo ,&nbsp;Weili Li ,&nbsp;Guanjing Ling ,&nbsp;Yan Wei ,&nbsp;Wei Wang ,&nbsp;Yong Wang","doi":"10.1016/j.semcancer.2025.01.004","DOIUrl":"10.1016/j.semcancer.2025.01.004","url":null,"abstract":"<div><div>Doxorubicin (DOX) is an anthracycline antitumor drug discovered in 1969, which can care for leukemia, breast cancer, lymphoma, and sarcoma. However, cardiotoxicity induced by DOX seriously limits its clinical value. The etiopathogenesis and therapeutic strategies are not unified. Autophagy is a critical mechanism in the progression of DOX-induced cardiotoxicity (DIC), autophagy intervention is a potential therapeutic strategy for DIC. Natural product has been considered as a complementary and alternative approach to treat cardiovascular disease. In this review, we summarize the pathology of autophagy in DIC and the natural products for DIC therapy.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"109 ","pages":"Pages 83-90"},"PeriodicalIF":12.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011113","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":"Decoding T cell senescence in cancer: Is revisiting required?","authors":"Sophia Magkouta ,&nbsp;Efrosyni Markaki ,&nbsp;Konstantinos Evangelou ,&nbsp;Russell Petty ,&nbsp;Panayotis Verginis ,&nbsp;Vassilis Gorgoulis","doi":"10.1016/j.semcancer.2024.11.003","DOIUrl":"10.1016/j.semcancer.2024.11.003","url":null,"abstract":"<div><div>Senescence is an inherent cellular mechanism triggered as a response to stressful insults. It associates with several aspects of cancer progression and therapy. Senescent cells constitute a highly heterogeneous cellular population and their identification can be very challenging. In fact, the term “senescence” has been often misused. This is also true in the case of immune cells. While several studies indicate the presence of senescent-like features (mainly in T cells), senescent immune cells are poorly described. Under this prism, we herein review the current literature on what has been characterized as T cell senescence and provide insights on how to accurately discriminate senescent cells against exhausted or anergic ones. We also summarize the major metabolic and epigenetic modifications associated with T cell senescence and underline the role of senescent T cells in the tumor microenvironment (TME). Moreover, we discuss how these cells associate with standard clinical therapeutic interventions and how they impact their efficacy. Finally, we underline the importance of precise identification and thorough characterization of “truly” senescent T cells in order to design successful therapeutic manipulations that would delay cancer incidence and maximize efficacy of immunotherapy.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"108 ","pages":"Pages 33-47"},"PeriodicalIF":12.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772014","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 senescence: A key player in cancer biology","authors":"Yanru Yang,&nbsp;Linni Fan,&nbsp;Mingyang Li,&nbsp;Zhe Wang","doi":"10.1016/j.semcancer.2024.12.001","DOIUrl":"10.1016/j.semcancer.2024.12.001","url":null,"abstract":"<div><div>With the rapid development of immunological techniques in recent years, our understanding of immune senescence has gradually deepened, but the role of immune senescence in cancer biology remains incompletely elucidated. Understanding these mechanisms and interactions is crucial for the development of tumor biology. This review examines five key areas: the classification and main features of immune senescence, factors influencing immune cell senescence in cancer, the reciprocal causal cycle between immune senescence and malignancy, and the potential of immune senescence as a target for cancer immunotherapy.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"108 ","pages":"Pages 71-82"},"PeriodicalIF":12.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829716","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":"Theoretical framework and emerging challenges of lipid metabolism in cancer","authors":"Qiuying Gu ,&nbsp;Yuan Wang ,&nbsp;Ping Yi ,&nbsp;Chunming Cheng","doi":"10.1016/j.semcancer.2024.12.002","DOIUrl":"10.1016/j.semcancer.2024.12.002","url":null,"abstract":"<div><div>Elevated lipid metabolism is one of hallmarks of malignant tumors. Lipids not only serve as essential structural components of biological membranes but also provide energy and substrates for the proliferation of cancer cells and tumor growth. Cancer cells meet their lipid needs by coordinating the processes of lipid absorption, synthesis, transport, storage, and catabolism. As research in this area continues to deepen, numerous new discoveries have emerged, making it crucial for scientists to stay informed about the developments of cancer lipid metabolism. In this review, we first discuss relevant concepts and theories or assumptions that help us understand the lipid metabolism and -based cancer therapies. We then systematically summarize the latest advancements in lipid metabolism including new mechanisms, novel targets, and up-to-date pre-clinical and clinical investigations of anti-cancer treatment with lipid metabolism targeted drugs. Finally, we emphasize emerging research directions and therapeutic strategies, and discuss future prospective and emerging challenges. This review aims to provide the latest insights and guidance for research in the field of cancer lipid metabolism.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"108 ","pages":"Pages 48-70"},"PeriodicalIF":12.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824485","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}