Seminars in cancer biology最新文献

{"title":"Extracellular vesicles associated microRNAs: Their biology and clinical significance as biomarkers in gastrointestinal cancers","authors":"Yuan Li ,&nbsp;Silei Sui ,&nbsp;Ajay Goel","doi":"10.1016/j.semcancer.2024.02.001","DOIUrl":"10.1016/j.semcancer.2024.02.001","url":null,"abstract":"<div><p>Gastrointestinal (GI) cancers, including colorectal, gastric, esophageal, pancreatic, and liver, are associated with high mortality and morbidity rates worldwide. One of the underlying reasons for the poor survival outcomes in patients with these malignancies is late disease detection, typically when the tumor has already advanced and potentially spread to distant organs. Increasing evidence indicates that earlier detection of these cancers is associated with improved survival outcomes and, in some cases, allows curative treatments. Consequently, there is a growing interest in the development of molecular biomarkers that offer promise for screening, diagnosis, treatment selection, response assessment, and predicting the prognosis of these cancers. Extracellular vesicles (EVs) are membranous vesicles released from cells containing a repertoire of biological molecules, including nucleic acids, proteins, lipids, and carbohydrates. MicroRNAs (miRNAs) are the most extensively studied non-coding RNAs, and the deregulation of miRNA levels is a feature of cancer cells. EVs miRNAs can serve as messengers for facilitating interactions between tumor cells and the cellular milieu, including immune cells, endothelial cells, and other tumor cells. Furthermore, recent years have witnessed considerable technological advances that have permitted in-depth sequence profiling of these small non-coding RNAs within EVs for their development as promising cancer biomarkers -particularly non-invasive, liquid biopsy markers in various cancers, including GI cancers. Herein, we summarize and discuss the roles of EV-associated miRNAs as they play a seminal role in GI cancer progression, as well as their promising translational and clinical potential as cancer biomarkers as we usher into the area of precision oncology.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"99 ","pages":"Pages 5-23"},"PeriodicalIF":14.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716354","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":"Special issue on “Excess body weight and cancer: Novel biologic insights and challenges”","authors":"Maria Dalamaga,&nbsp;Nikolaos Spyrou","doi":"10.1016/j.semcancer.2024.01.002","DOIUrl":"10.1016/j.semcancer.2024.01.002","url":null,"abstract":"","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"99 ","pages":"Pages 1-4"},"PeriodicalIF":14.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564470","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 obesity-autophagy-cancer axis: Mechanistic insights and therapeutic perspectives","authors":"Amir Barzegar Behrooz ,&nbsp;Marco Cordani ,&nbsp;Alessandra Fiore ,&nbsp;Massimo Donadelli ,&nbsp;Joseph W. Gordon ,&nbsp;Daniel J. Klionsky ,&nbsp;Saeid Ghavami","doi":"10.1016/j.semcancer.2024.01.003","DOIUrl":"10.1016/j.semcancer.2024.01.003","url":null,"abstract":"<div><p>Autophagy, a self-degradative process vital for cellular homeostasis, plays a significant role in adipose tissue metabolism and tumorigenesis. This review aims to elucidate the complex interplay between autophagy, obesity, and cancer development, with a specific emphasis on how obesity-driven changes affect the regulation of autophagy and subsequent implications for cancer risk. The burgeoning epidemic of obesity underscores the relevance of this research, particularly given the established links between obesity, autophagy, and various cancers. Our exploration delves into hormonal influence, notably INS (insulin) and LEP (leptin), on obesity and autophagy interactions. Further, we draw attention to the latest findings on molecular factors linking obesity to cancer, including hormonal changes, altered metabolism, and secretory autophagy. We posit that targeting autophagy modulation may offer a potent therapeutic approach for obesity-associated cancer, pointing to promising advancements in nanocarrier-based targeted therapies for autophagy modulation. However, we also recognize the challenges inherent to these approaches, particularly concerning their precision, control, and the dual roles autophagy can play in cancer. Future research directions include identifying novel biomarkers, refining targeted therapies, and harmonizing these approaches with precision medicine principles, thereby contributing to a more personalized, effective treatment paradigm for obesity-mediated cancer.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"99 ","pages":"Pages 24-44"},"PeriodicalIF":14.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X24000099/pdfft?md5=8b195c978156e3d1e5deac5220e8982f&pid=1-s2.0-S1044579X24000099-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668906","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":"Editorial: Regulating cell cycle-related activities: The right target for cancer therapy","authors":"Hang Fai Kwok","doi":"10.1016/j.semcancer.2024.01.001","DOIUrl":"10.1016/j.semcancer.2024.01.001","url":null,"abstract":"","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"98 ","pages":"Pages 64-65"},"PeriodicalIF":14.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X24000014/pdfft?md5=ee1ee1de72d71fa5080c4d5b2f3828b8&pid=1-s2.0-S1044579X24000014-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139462657","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":"Corrigendum to “Microbe-based therapies for colorectal cancer: Advantages and limitations” [Semin. Cancer Biol. 86 (2022) 652–665]","authors":"M. Saeed ,&nbsp;A. Shoaib ,&nbsp;R. Kandimalla ,&nbsp;S. Javed ,&nbsp;A. Almatroudi ,&nbsp;R. Gupta ,&nbsp;F. Aqil","doi":"10.1016/j.semcancer.2023.12.003","DOIUrl":"10.1016/j.semcancer.2023.12.003","url":null,"abstract":"","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"98 ","pages":"Page 66"},"PeriodicalIF":14.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X23001608/pdfft?md5=c5c1e8697c3d64b637faad91e056ba33&pid=1-s2.0-S1044579X23001608-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139486144","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":"Beyond cell cycle regulation: The pleiotropic function of CDK4 in cancer","authors":"Dorian V. Ziegler ,&nbsp;Kanishka Parashar ,&nbsp;Lluis Fajas","doi":"10.1016/j.semcancer.2023.12.002","DOIUrl":"10.1016/j.semcancer.2023.12.002","url":null,"abstract":"<div><p>CDK4, along with its regulatory subunit, cyclin D, drives the transition from G1 to S phase, during which DNA replication and metabolic activation occur. In this canonical pathway, CDK4 is essentially a transcriptional regulator that acts through phosphorylation of retinoblastoma protein (RB) and subsequent activation of the transcription factor E2F, ultimately triggering the expression of genes involved in DNA synthesis and cell cycle progression to S phase. In this review, we focus on the newly reported functions of CDK4, which go beyond direct regulation of the cell cycle. In particular, we describe the extranuclear roles of CDK4, including its roles in the regulation of metabolism, cell fate, cell dynamics and the tumor microenvironment. We describe direct phosphorylation targets of CDK4 and decipher how CDK4 influences these physiological processes in the context of cancer.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"98 ","pages":"Pages 51-63"},"PeriodicalIF":14.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X23001591/pdfft?md5=a4f24c0188ee2ae8cf554585ba052003&pid=1-s2.0-S1044579X23001591-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138885912","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":"Deregulated transcription factors in the emerging cancer hallmarks","authors":"Adria Hasan ,&nbsp;Naushad Ahmad Khan ,&nbsp;Shahab Uddin ,&nbsp;Abdul Q. Khan ,&nbsp;Martin Steinhoff","doi":"10.1016/j.semcancer.2023.12.001","DOIUrl":"10.1016/j.semcancer.2023.12.001","url":null,"abstract":"<div><p>Cancer progression is a multifaceted process that entails several stages and demands the persistent expression or activation of transcription factors (TFs) to facilitate growth and survival. TFs are a cluster of proteins with DNA-binding domains that attach to promoter or enhancer DNA strands to start the transcription of genes by collaborating with RNA polymerase and other supporting proteins. They are generally acknowledged as the major regulatory molecules that coordinate biological homeostasis and the appropriate functioning of cellular components, subsequently contributing to human physiology. TFs proteins are crucial for controlling transcription during the embryonic stage and development, and the stability of different cell types depends on how they function in different cell types. The development and progression of cancer cells and tumors might be triggered by any anomaly in transcription factor function. It has long been acknowledged that cancer development is accompanied by the dysregulated activity of TF alterations which might result in faulty gene expression. Recent studies have suggested that dysregulated transcription factors play a major role in developing various human malignancies by altering and rewiring metabolic processes, modifying the immune response, and triggering oncogenic signaling cascades. This review emphasizes the interplay between TFs involved in metabolic and epigenetic reprogramming, evading immune attacks, cellular senescence, and the maintenance of cancer stemness in cancerous cells. The insights presented herein will facilitate the development of innovative therapeutic modalities to tackle the dysregulated transcription factors underlying cancer.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"98 ","pages":"Pages 31-50"},"PeriodicalIF":14.5,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X2300158X/pdfft?md5=8d19160c82caf1bfc8b7e2414e89ebac&pid=1-s2.0-S1044579X2300158X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138740901","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 as a potential inducer of immune tolerance, tumor plasticity and a driver of tumor mutational burden: Impact on cancer immunotherapy","authors":"Raefa Abou Khouzam ,&nbsp;Bassam Janji ,&nbsp;Jerome Thiery ,&nbsp;Rania Faouzi Zaarour ,&nbsp;Ali N. Chamseddine ,&nbsp;Hemma Mayr ,&nbsp;Pierre Savagner ,&nbsp;Claudine Kieda ,&nbsp;Sophie Gad ,&nbsp;Stéphanie Buart ,&nbsp;Jean–Marie Lehn ,&nbsp;Perparim Limani ,&nbsp;Salem Chouaib","doi":"10.1016/j.semcancer.2023.11.008","DOIUrl":"10.1016/j.semcancer.2023.11.008","url":null,"abstract":"<div><p>In cancer patients, immune cells<span> are often functionally compromised due to the immunosuppressive features of the tumor microenvironment (TME) which contribute to the failures in cancer therapies. Clinical and experimental evidence indicates that developing tumors adapt to the immunological environment and create a local microenvironment that impairs immune function by inducing immune tolerance<span><span> and invasion. In this context, microenvironmental hypoxia, which is an established hallmark of solid tumors, significantly contributes to tumor aggressiveness and therapy resistance through the induction of tumor plasticity/heterogeneity and, more importantly, through the differentiation and expansion of immune-suppressive stromal cells. We and others have provided evidence indicating that hypoxia also drives </span>genomic instability<span><span> in cancer cells and interferes with DNA damage response<span> and repair suggesting that hypoxia could be a potential driver of tumor mutational burden. Here, we reviewed the current knowledge on how hypoxic stress in the TME impacts tumor angiogenesis, heterogeneity, plasticity, and immune resistance, with a special interest in tumor immunogenicity and hypoxia targeting. An integrated understanding of the complexity of the effect of hypoxia on the immune and microenvironmental components could lead to the identification of better adapted and more effective combinational strategies in </span></span>cancer immunotherapy. Clearly, the discovery and validation of therapeutic targets derived from the hypoxic tumor microenvironment is of major importance and the identification of critical hypoxia-associated pathways could generate targets that are undeniably attractive for combined cancer immunotherapy approaches.</span></span></span></p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"97 ","pages":"Pages 104-123"},"PeriodicalIF":14.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462425","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":"Mutual regulation of TGFβ-induced oncogenic EMT, cell cycle progression and the DDR","authors":"Harald Schuhwerk ,&nbsp;Thomas Brabletz","doi":"10.1016/j.semcancer.2023.11.009","DOIUrl":"10.1016/j.semcancer.2023.11.009","url":null,"abstract":"<div><p>TGFβ signaling and the DNA damage response (DDR) are two cellular toolboxes with a strong impact on cancer biology. While TGFβ as a pleiotropic cytokine affects essentially all hallmarks of cancer, the multifunctional DDR mostly orchestrates cell cycle progression, DNA repair, chromatin remodeling and cell death. One oncogenic effect of TGFβ is the partial activation of epithelial-to-mesenchymal transition (EMT), conferring invasiveness, cellular plasticity and resistance to various noxae. Several reports show that both individual networks as well as their interface affect chemo-/radiotherapies. However, the underlying mechanisms remain poorly resolved. EMT often correlates with TGFβ-induced slowing of proliferation, yet numerous studies demonstrate that particularly the co-activated EMT transcription factors counteract anti-proliferative signaling in a partially non-redundant manner. Collectively, evidence piled up over decades underscore a multifaceted, reciprocal inter-connection of TGFβ signaling / EMT with the DDR / cell cycle progression, which we will discuss here. Altogether, we conclude that full cell cycle arrest is barely compatible with the propagation of oncogenic EMT traits and further propose that ‘EMT-linked DDR plasticity’ is a crucial, yet intricate facet of malignancy, decisively affecting metastasis formation and therapy resistance.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"97 ","pages":"Pages 86-103"},"PeriodicalIF":14.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1044579X23001499/pdfft?md5=36548423bca3bf1d1048418a0e30fb2f&pid=1-s2.0-S1044579X23001499-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462426","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":"One label is all you need: Interpretable AI-enhanced histopathology for oncology","authors":"Thomas E. Tavolara,&nbsp;Ziyu Su,&nbsp;Metin N. Gurcan,&nbsp;M. Khalid Khan Niazi","doi":"10.1016/j.semcancer.2023.09.006","DOIUrl":"10.1016/j.semcancer.2023.09.006","url":null,"abstract":"<div><p><span><span>Artificial Intelligence (AI)-enhanced histopathology presents unprecedented opportunities to benefit oncology through interpretable methods that require only one overall label per hematoxylin and eosin (H&amp;E) slide with no tissue-level annotations. We present a structured review of these methods organized by their degree of verifiability and by commonly recurring application areas in oncological characterization. First, we discuss morphological markers (tumor presence/absence, metastases, subtypes, grades) in which AI-identified regions of interest (ROIs) within whole slide images (WSIs) verifiably overlap with pathologist-identified ROIs. Second, we discuss </span>molecular markers<span> (gene expression, molecular subtyping) that are not verified via H&amp;E but rather based on overlap with positive regions on adjacent tissue. Third, we discuss genetic markers (mutations, mutational burden, microsatellite instability, chromosomal instability) that current technologies cannot verify if AI methods spatially resolve specific </span></span>genetic alterations. Fourth, we discuss the direct prediction of survival to which AI-identified histopathological features quantitatively correlate but are nonetheless not mechanistically verifiable. Finally, we discuss in detail several opportunities and challenges for these one-label-per-slide methods within oncology. Opportunities include reducing the cost of research and clinical care, reducing the workload of clinicians, personalized medicine, and unlocking the full potential of histopathology through new imaging-based biomarkers. Current challenges include explainability and interpretability, validation via adjacent tissue sections, reproducibility, data availability, computational needs, data requirements, domain adaptability, external validation, dataset imbalances, and finally commercialization and clinical potential. Ultimately, the relative ease and minimum upfront cost with which relevant data can be collected in addition to the plethora of available AI methods for outcome-driven analysis will surmount these current limitations and achieve the innumerable opportunities associated with AI-driven histopathology for the benefit of oncology.</p></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"97 ","pages":"Pages 70-85"},"PeriodicalIF":14.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41211345","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}