Seminars in cancer biology最新文献

{"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}

{"title":"Multifaceted effects of obesity on cancer immunotherapies: Bridging preclinical models and clinical data","authors":"Logan V. Vick ,&nbsp;Robert J. Canter ,&nbsp;Arta M. Monjazeb ,&nbsp;William J. Murphy","doi":"10.1016/j.semcancer.2023.07.004","DOIUrl":"10.1016/j.semcancer.2023.07.004","url":null,"abstract":"<div><p>Obesity, defined by excessive body fat, is a highly complex condition affecting numerous physiological processes, such as metabolism, proliferation, and cellular homeostasis. These multifaceted effects impact cells and tissues throughout the host, including immune cells as well as cancer biology. Because of the multifaceted nature of obesity, common parameters used to define it (such as body mass index in humans) can be problematic, and more nuanced methods are needed to characterize the pleiotropic metabolic effects of obesity. Obesity is well-accepted as an overall negative prognostic factor for cancer incidence, progression, and outcome. This is in part due to the meta-inflammatory and immunosuppressive effects of obesity. Immunotherapy is increasingly used in cancer therapy, and there are many different types of immunotherapy approaches. The effects of obesity on immunotherapy have only recently been studied with the demonstration of an “obesity paradox”, in which some immune therapies have been demonstrated to result in greater efficacy in obese subjects despite the direct adverse effects of obesity and excess body fat acting on the cancer itself. The multifactorial characteristics that influence the effects of obesity (age, sex, lean muscle mass, underlying metabolic conditions and drugs) further confound interpretation of clinical data and necessitate the use of more relevant preclinical models mirroring these variables in the human scenario. Such models will allow for more nuanced mechanistic assessment of how obesity can impact, both positively and negatively, cancer biology, host metabolism, immune regulation, and how these intersecting processes impact the delivery and outcome of cancer immunotherapy.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"95 ","pages":"Pages 88-102"},"PeriodicalIF":14.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520413","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":"Enhancing head and neck tumor management with artificial intelligence: Integration and perspectives","authors":"Nian-Nian Zhong ,&nbsp;Han-Qi Wang ,&nbsp;Xin-Yue Huang ,&nbsp;Zi-Zhan Li ,&nbsp;Lei-Ming Cao ,&nbsp;Fang-Yi Huo ,&nbsp;Bing Liu ,&nbsp;Lin-Lin Bu","doi":"10.1016/j.semcancer.2023.07.002","DOIUrl":"10.1016/j.semcancer.2023.07.002","url":null,"abstract":"<div><p>Head and neck tumors (HNTs) constitute a multifaceted ensemble of pathologies that primarily involve regions such as the oral cavity, pharynx, and nasal cavity. The intricate anatomical structure of these regions poses considerable challenges to efficacious treatment strategies. Despite the availability of myriad treatment modalities, the overall therapeutic efficacy for HNTs continues to remain subdued. In recent years, the deployment of artificial intelligence (AI) in healthcare practices has garnered noteworthy attention. AI modalities, inclusive of machine learning (ML), neural networks (NNs), and deep learning (DL), when amalgamated into the holistic management of HNTs, promise to augment the precision, safety, and efficacy of treatment regimens. The integration of AI within HNT management is intricately intertwined with domains such as medical imaging, bioinformatics, and medical robotics. This article intends to scrutinize the cutting-edge advancements and prospective applications of AI in the realm of HNTs, elucidating AI’s indispensable role in prevention, diagnosis, treatment, prognostication, research, and inter-sectoral integration. The overarching objective is to stimulate scholarly discourse and invigorate insights among medical practitioners and researchers to propel further exploration, thereby facilitating superior therapeutic alternatives for patients.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"95 ","pages":"Pages 52-74"},"PeriodicalIF":14.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166293","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":"Proactive and reactive roles of TGF-β in cancer","authors":"Nick A. Kuburich ,&nbsp;Thiru Sabapathy ,&nbsp;Breanna R. Demestichas ,&nbsp;Joanna Joyce Maddela ,&nbsp;Petra den Hollander ,&nbsp;Sendurai A. Mani","doi":"10.1016/j.semcancer.2023.08.002","DOIUrl":"10.1016/j.semcancer.2023.08.002","url":null,"abstract":"<div><p>Cancer cells adapt to varying stress conditions to survive through plasticity. Stem cells exhibit a high degree of plasticity, allowing them to generate more stem cells or differentiate them into specialized cell types to contribute to tissue development, growth, and repair. Cancer cells can also exhibit plasticity and acquire properties that enhance their survival. TGF-β is an unrivaled growth factor exploited by cancer cells to gain plasticity. TGF-β-mediated signaling enables carcinoma cells to alter their epithelial and mesenchymal properties through epithelial-mesenchymal plasticity (EMP). However, TGF-β is a multifunctional cytokine; thus, the signaling by TGF-β can be detrimental or beneficial to cancer cells depending on the cellular context. Those cells that overcome the anti-tumor effect of TGF-β can induce epithelial-mesenchymal transition (EMT) to gain EMP benefits. EMP allows cancer cells to alter their cell properties and the tumor immune microenvironment (TIME), facilitating their survival. Due to the significant roles of TGF-β and EMP in carcinoma progression, it is essential to understand how TGF-β enables EMP and how cancer cells exploit this plasticity. This understanding will guide the development of effective TGF-β-targeting therapies that eliminate cancer cell plasticity.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"95 ","pages":"Pages 120-139"},"PeriodicalIF":14.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166819","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}