Seminars in cancer biology最新文献

{"title":"Mathematical modeling of cardio-oncology: Modeling the systemic effects of cancer therapeutics on the cardiovascular system","authors":"Camara L. Casson ,&nbsp;Sofia A. John ,&nbsp;Meghan C. Ferrall-Fairbanks","doi":"10.1016/j.semcancer.2023.11.004","DOIUrl":"10.1016/j.semcancer.2023.11.004","url":null,"abstract":"<div><p>Cardiotoxicity is a common side-effect of many cancer therapeutics; however, to-date there has been very little push to understand the mechanisms underlying this group of pathologies. This has led to the emergence of cardio-oncology, a field of medicine focused on understanding the effects of cancer and its treatment on the human heart. Here, we describe how mechanistic modeling approaches have been applied to study open questions in the cardiovascular system and how these approaches are being increasingly applied to advance knowledge of the underlying effects of cancer treatments on the human heart. A variety of mechanistic, mathematical modeling techniques have been applied to explore the link between common cancer treatments, such as chemotherapy, radiation, targeted therapy, and immunotherapy, and cardiotoxicity, nevertheless there is limited coverage in the different types of cardiac dysfunction that may be associated with these treatments. Moreover, cardiac modeling has a rich heritage of mathematical modeling and is well suited for the further development of novel approaches for understanding the cardiotoxicities associated with cancer therapeutics. There are many opportunities to combine mechanistic, bottom-up approaches with data-driven, top-down approaches to improve personalized, precision oncology to better understand, and ultimately mitigate, cardiac dysfunction in cancer patients.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"97 ","pages":"Pages 30-41"},"PeriodicalIF":14.5,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X23001438/pdfft?md5=93f6da9919c765701550a9f17dbddd8a&pid=1-s2.0-S1044579X23001438-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047838","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":"Application of artificial intelligence in oncology","authors":"Xuelei Ma,&nbsp;Qi Zhao","doi":"10.1016/j.semcancer.2023.11.005","DOIUrl":"10.1016/j.semcancer.2023.11.005","url":null,"abstract":"","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"97 ","pages":"Pages 68-69"},"PeriodicalIF":14.5,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136399021","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":"Thinking small to win big? A critical review on the potential application of extracellular vesicles for biomarker discovery and new therapeutic approaches in pancreatic cancer","authors":"Mahrou Vahabi ,&nbsp;Annalisa Comandatore ,&nbsp;Chiara Centra ,&nbsp;Giovanni Blandino ,&nbsp;Luca Morelli ,&nbsp;Elisa Giovannetti","doi":"10.1016/j.semcancer.2023.11.003","DOIUrl":"10.1016/j.semcancer.2023.11.003","url":null,"abstract":"<div><p>Pancreatic ductal adenocarcinoma (PDAC) is an extremely deadly form of cancer, with limited progress in 5-year survival rates despite significant research efforts. The main challenges in treating PDAC include difficulties in early detection, and resistance to current therapeutic approaches due to aggressive molecular and microenvironment features. These challenges emphasize the importance of identifying clinically validated biomarkers for early detection and clinical management. Extracellular vesicles (EVs), particularly exosomes, have emerged as crucial mediators of intercellular communication by transporting molecular cargo. Recent research has unveiled their role in initiation, metastasis, and chemoresistance of PDAC. Consequently, utilizing EVs in liquid biopsies holds promise for the identification of biomarkers for early detection, prognosis, and monitoring of drug efficacy. However, numerous limitations, including challenges in isolation and characterization of homogeneous EVs populations, as well as the absence of standardized protocols, can affect the reliability of studies involving EVs as biomarkers, underscoring the necessity for a prudent approach. EVs have also garnered considerable attention as a promising drug delivery system and novel therapy for tumors. The loading of biomolecules or chemical drugs into exosomes and their subsequent delivery to target cells can effectively impede tumor progression. Nevertheless, there are obstacles that must be overcome to ensure the accuracy and efficacy of therapies relying on EVs for the treatment of tumors. In this review, we examine both recent advancements and remaining obstacles, exploring the potential of utilizing EVs in biomarker discovery as well as for the development of drug delivery vehicles.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"97 ","pages":"Pages 50-67"},"PeriodicalIF":14.5,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X23001360/pdfft?md5=173c9cc7a0850568e37008eead652550&pid=1-s2.0-S1044579X23001360-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135664613","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":"TGF-β, EMT, and resistance to anti-cancer treatment","authors":"Xuecong Wang ,&nbsp;Pieter Johan Adam Eichhorn ,&nbsp;Jean Paul Thiery","doi":"10.1016/j.semcancer.2023.10.004","DOIUrl":"10.1016/j.semcancer.2023.10.004","url":null,"abstract":"<div><p>Transforming growth factor-β (TGF-β) signaling regulates cell-specific programs involved in embryonic development, wound-healing, and immune homeostasis. Yet, during tumor progression, these TGF-β-mediated programs are altered, leading to epithelial cell plasticity and a reprogramming of epithelial cells into mesenchymal lineages through epithelial-to-mesenchymal transition (EMT), a critical developmental program in morphogenesis and organogenesis. These changes, in turn, lead to enhanced carcinoma cell invasion, metastasis, immune cell differentiation, immune evasion, and chemotherapy resistance. Here, we discuss EMT as one of the critical programs associated with carcinoma cell plasticity and the influence exerted by TGF-β on carcinoma status and function. We further explore the composition of carcinoma and other cell populations within the tumor microenvironment, and consider the relevant outcomes related to the programs associated with cancer treatment resistance.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"97 ","pages":"Pages 1-11"},"PeriodicalIF":14.5,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X23001335/pdfft?md5=1289edc3bf4861cf8d3d13271692b8aa&pid=1-s2.0-S1044579X23001335-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72015270","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":"Hypoxia signaling and metastatic progression","authors":"Luana Schito ,&nbsp;Sergio Rey-Keim","doi":"10.1016/j.semcancer.2023.11.001","DOIUrl":"10.1016/j.semcancer.2023.11.001","url":null,"abstract":"<div><p>Disruption of oxygen homeostasis, resulting from an imbalance between O₂ supply and demand during malignant proliferation, leads to the development of hypoxic tumor microenvironments that promote the acquisition of aggressive cancer cell phenotypes linked to metastasis and patient mortality. In this review, the mechanistic links between tumor hypoxia and metastatic progression are presented. Current status and perspectives of targeting hypoxia signaling pathways as a strategy to halt cancer cell metastatic activities are emphasized.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"97 ","pages":"Pages 42-49"},"PeriodicalIF":14.5,"publicationDate":"2023-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X23001347/pdfft?md5=0ed65e901b78ac94e7fe5ae01511e96e&pid=1-s2.0-S1044579X23001347-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71485684","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":"Obesity associated pancreatic ductal adenocarcinoma: Therapeutic challenges","authors":"Mundla Srilatha ,&nbsp;Ramarao Malla ,&nbsp;Megha Priya Adem ,&nbsp;Jeremy B. Foote ,&nbsp;Ganji Purnachandra Nagaraju","doi":"10.1016/j.semcancer.2023.11.002","DOIUrl":"10.1016/j.semcancer.2023.11.002","url":null,"abstract":"<div><p>Obesity is a prominent health issue worldwide and directly impacts pancreatic health, with obese individuals exhibiting a significant risk for increasing pancreatic ductal adenocarcinoma (PDAC). Several factors potentially explain the increased risk for the development of PDAC, including obesity-induced chronic inflammation within and outside of the pancreas, development of insulin resistance and metabolic dysfunction, promotion of immune suppression within the pancreas during inflammation, pre- and malignant stages, variations in hormones levels (adiponectin, ghrelin, and leptin) produced from the adipose tissue, and acquisition of somatic mutations in tumor once- and suppressor proteins critical for pancreatic tumorigenesis. In this manuscript, we will explore the broad impact of these obesity-induced risk factors on the development and progression of PDAC, focusing on changes within the tumor microenvironment (TME) as they pertain to prevention, current therapeutic strategies, and future directions for targeting obesity management as they relate to the prevention of pancreatic tumorigenesis.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"97 ","pages":"Pages 12-20"},"PeriodicalIF":14.5,"publicationDate":"2023-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X23001359/pdfft?md5=74a4a7208e69d203a204322e1c0fe9fd&pid=1-s2.0-S1044579X23001359-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71485685","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 shape-shifting embryonic cells to oncology: The fascinating history of epithelial mesenchymal transition","authors":"Rosemary J. Akhurst","doi":"10.1016/j.semcancer.2023.10.003","DOIUrl":"10.1016/j.semcancer.2023.10.003","url":null,"abstract":"<div><p>Epithelial-to-mesenchymal transition or transformation (EMT) is a cell shape-changing process that is utilized repeatedly throughout embryogenesis and is critical to the attainment of a precise body plan. In the adult, EMT is observed under both normal and pathological conditions, such as during normal wounding healing, during development of certain fibrotic states and vascular anomalies, as well as in some cancers when malignant cells progress to become more aggressive, invasive, and metastatic. Epithelia derived from any of the three embryonic germ layers can undergo EMT, including those derived from mesoderm, such as endothelial cells (sometimes termed Endo-MT) and those derived from endoderm such as fetal liver stroma. At the cellular level, EMT is defined as the transformation of epithelial cells towards a mesenchymal phenotype and is marked by attenuation of expression of epithelial markers and <em>de novo</em> expression of mesenchymal markers. This process is induced by extracellular factors and can be reversible, resulting in mesenchymal-to-epithelial transformation (MET). It is now clear that a cell can simultaneously express properties of both epithelia and mesenchyme, and that such transitional cell-types drive tumor cell heterogeneity, an important aspect of cancer progression, development of a stem-like cell state, and drug resistance. Here we review some of the earliest studies demonstrating the existence of EMT during embryogenesis and discuss the discovery of the extracellular factors and intracellular signaling pathways that contribute to this process, with components of the TGFβ signaling superfamily playing a prominent role. We mention early controversies surrounding <em>in vivo</em> EMT during embryonic development and in adult diseased states, and the maturation of the field to a stage wherein targeting EMT to control disease states is an aspirational goal.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"96 ","pages":"Pages 100-114"},"PeriodicalIF":14.5,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49681901","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":"Extracellular vesicles as a potential delivery platform for CRISPR-Cas based therapy in epithelial ovarian cancer","authors":"Nihar Godbole ,&nbsp;Alexander Quinn ,&nbsp;Flavio Carrion ,&nbsp;Emanuele Pelosi ,&nbsp;Carlos Salomon","doi":"10.1016/j.semcancer.2023.10.002","DOIUrl":"10.1016/j.semcancer.2023.10.002","url":null,"abstract":"<div><p>Ovarian Cancer (OC) is the most common gynecological malignancy and the eighth most diagnosed cancer in females worldwide. Presently, it ranks as the fifth leading cause of cancer-related mortality among patients globally. Major factors contributing to the lethality of OC worldwide include delayed diagnosis, chemotherapy resistance, high metastatic rates, and the heterogeneity of subtypes. Despite continuous efforts to develop novel targeted therapies and chemotherapeutic agents, challenges persist in the form of OC resistance and recurrence. In the last decade, CRISPR-Cas-based genome editing has emerged as a powerful tool for modifying genetic and epigenetic mechanisms, holding potential for treating numerous diseases. However, a significant challenge for therapeutic applications of CRISPR-Cas technology is the absence of an optimal vehicle for delivering CRISPR molecular machinery into targeted cells or tissues. Recently, extracellular vesicles (EVs) have gained traction as potential delivery vehicles for various therapeutic agents. These heterogeneous, membrane-derived vesicles are released by nearly all cells into extracellular spaces. They carry a molecular cargo of proteins and nucleic acids within their intraluminal space, encased by a cholesterol-rich phospholipid bilayer membrane. EVs actively engage in cell-to-cell communication by delivering cargo to both neighboring and distant cells. Their inherent ability to shield molecular cargo from degradation and cross biological barriers positions them ideally for delivering CRISPR-Cas ribonucleoproteins (RNP) to target cells. Furthermore, they exhibit higher biocompatibility, lower immunogenicity, and reduced toxicity compared to classical delivery platforms such as adeno-associated virus, lentiviruses, and synthetic nanoparticles. This review explores the potential of employing different CRISPR-Cas systems to target specific genes in OC, while also discussing various methods for engineering EVs to load CRISPR components and enhance their targeting capabilities.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"96 ","pages":"Pages 64-81"},"PeriodicalIF":14.5,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41211346","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":"Transcriptional regulation of EMT transcription factors in cancer","authors":"Masao Saitoh","doi":"10.1016/j.semcancer.2023.10.001","DOIUrl":"10.1016/j.semcancer.2023.10.001","url":null,"abstract":"<div><p>The epithelial–mesenchymal transition (EMT) is one of the processes by which epithelial cells transdifferentiate into mesenchymal cells in the developmental stage, known as “complete EMT.” In epithelial cancer, EMT, also termed “partial EMT,” is associated with invasion, metastasis, and resistance to therapy, and is elicited by several transcription factors, frequently referred to as EMT transcription factors. Among these transcription factors that regulate EMT, ZEB1/2 (ZEB1 and ZEB2), SNAIL, and TWIST play a prominent role in driving the EMT process (hereafter referred to as “EMT-TFs”). Among these, ZEB1/2 show positive correlation with both expression of mesenchymal marker proteins and the aggressiveness of various carcinomas. On the other hand, TWIST and SNAIL are also correlated with the aggressiveness of carcinomas, but are not highly correlated with mesenchymal marker protein expression. Interestingly, these EMT-TFs are not detected simultaneously in any studied cases of aggressive cancers, except for sarcoma. Thus, only one or some of the EMT-TFs are expressed at high levels in cells of aggressive carcinomas. Expression of EMT-TFs is regulated by transforming growth factor-β (TGF-β), a well-established inducer of EMT, in cooperation with other signaling molecules, such as active RAS signals. The focus of this review is the molecular mechanisms by which EMT-TFs are transcriptionally sustained at sufficiently high levels in cells of aggressive carcinomas and upregulated by TGF-β during cancer progression.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"97 ","pages":"Pages 21-29"},"PeriodicalIF":14.5,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X2300130X/pdfft?md5=891b9392b101dde06a2a24a23f78907f&pid=1-s2.0-S1044579X2300130X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41150825","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 emerging regulatory roles of non-coding RNAs associated with glucose metabolism in breast cancer","authors":"Samarth Kansara ,&nbsp;Agrata Singh ,&nbsp;Abhishesh Kumar Badal ,&nbsp;Reshma Rani ,&nbsp;Prakash Baligar ,&nbsp;Manoj Garg ,&nbsp;Amit Kumar Pandey","doi":"10.1016/j.semcancer.2023.06.007","DOIUrl":"10.1016/j.semcancer.2023.06.007","url":null,"abstract":"<div><p><span><span>Altered energy metabolism is one of the hallmarks of tumorigenesis and essential for fulfilling the high demand for metabolic energy in a tumor through accelerating glycolysis and reprogramming the glycolysis metabolism through the Warburg effect. The dysregulated glucose metabolic pathways are coordinated not only by proteins coding genes but also by non-coding RNAs (ncRNAs) during the initiation and cancer progression. The ncRNAs are responsible for regulating numerous cellular processes under developmental and pathological conditions. Recent studies have shown that various ncRNAs such as </span>microRNAs<span>, circular RNAs<span>, and long noncoding RNAs are extensively involved in rewriting </span></span></span>glucose metabolism in human cancers. In this review, we demonstrated the role of ncRNAs in the progression of breast cancer with a focus on outlining the aberrant expression of glucose metabolic pathways. Moreover, we have discussed the existing and probable future applications of ncRNAs to regulate energy pathways along with their importance in the prognosis, diagnosis, and future therapeutics for human breast carcinoma.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"95 ","pages":"Pages 1-12"},"PeriodicalIF":14.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168546","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}