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The UPRising connection between endoplasmic reticulum stress and the tumor microenvironment. 内质网应激与肿瘤微环境之间的联系日益突出。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-01 Epub Date: 2024-10-29 DOI: 10.1016/j.trecan.2024.09.011
Hery Urra, Raúl Aravena, Lucas González-Johnson, Claudio Hetz
{"title":"The UPRising connection between endoplasmic reticulum stress and the tumor microenvironment.","authors":"Hery Urra, Raúl Aravena, Lucas González-Johnson, Claudio Hetz","doi":"10.1016/j.trecan.2024.09.011","DOIUrl":"10.1016/j.trecan.2024.09.011","url":null,"abstract":"<p><p>The tumor microenvironment (TME) represents a dynamic network of cancer cells, stromal cells, immune mediators, and extracellular matrix components, crucial for cancer progression. Stress conditions such as oncogene activation, nutrient deprivation, and hypoxia disrupt the endoplasmic reticulum (ER), activating the unfolded protein response (UPR), the main adaptive mechanism to restore ER function. The UPR regulates cancer progression by engaging cell-autonomous and cell-non-autonomous mechanisms, reprogramming the stroma and promoting immune evasion, angiogenesis, and invasion. This review explores the role of UPR beyond cancer cells, focusing on how ER stress signaling reshapes the TME, supporting tumor growth. The therapeutic potential of targeting the UPR is also discussed.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1161-1173"},"PeriodicalIF":14.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547714","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}
引用次数: 0
Crosstalk of T cells within the ovarian cancer microenvironment. 卵巢癌微环境中 T 细胞的相互影响。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI: 10.1016/j.trecan.2024.09.001
Bovannak S Chap, Nicolas Rayroux, Alizée J Grimm, Eleonora Ghisoni, Denarda Dangaj Laniti
{"title":"Crosstalk of T cells within the ovarian cancer microenvironment.","authors":"Bovannak S Chap, Nicolas Rayroux, Alizée J Grimm, Eleonora Ghisoni, Denarda Dangaj Laniti","doi":"10.1016/j.trecan.2024.09.001","DOIUrl":"10.1016/j.trecan.2024.09.001","url":null,"abstract":"<p><p>Ovarian cancer (OC) represents ecosystems of highly diverse tumor microenvironments (TMEs). The presence of tumor-infiltrating lymphocytes (TILs) is linked to enhanced immune responses and long-term survival. In this review we present emerging evidence suggesting that cellular crosstalk tightly regulates the distribution of TILs within the TME, underscoring the need to better understand key cellular networks that promote or impede T cell infiltration in OC. We also capture the emergent methodologies and computational techniques that enable the dissection of cell-cell crosstalk. Finally, we present innovative ex vivo TME models that can be leveraged to map and perturb cellular communications to enhance T cell infiltration and immune reactivity.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1116-1130"},"PeriodicalIF":14.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354698","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}
引用次数: 0
Engineering growth factor ligands and receptors for therapeutic innovation. 对生长因子配体和受体进行工程设计，以实现治疗创新。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-01 Epub Date: 2024-10-10 DOI: 10.1016/j.trecan.2024.09.006
Xinran An, Justin Paoloni, Yuseong Oh, Jamie B Spangler
{"title":"Engineering growth factor ligands and receptors for therapeutic innovation.","authors":"Xinran An, Justin Paoloni, Yuseong Oh, Jamie B Spangler","doi":"10.1016/j.trecan.2024.09.006","DOIUrl":"10.1016/j.trecan.2024.09.006","url":null,"abstract":"<p><p>Growth factors signal through engagement and activation of their respective cell surface receptors to choreograph an array of cellular functions, including proliferation, growth, repair, migration, differentiation, and survival. Because of their vital role in determining cell fate and maintaining homeostasis, dysregulation of growth factor pathways leads to the development and/or progression of disease, particularly in the context of cancer. Exciting advances in protein engineering technologies have enabled innovative strategies to redesign naturally occurring growth factor ligands and receptors as targeted therapeutics. We review growth factor protein engineering efforts, including affinity modulation, molecular fusion, the design of decoy receptors, dual specificity constructs, and vaccines. Collectively, these approaches are catapulting next-generation drugs to treat cancer and a host of other conditions.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1131-1146"},"PeriodicalIF":14.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401444","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}
引用次数: 0
Epigenetic reprogramming in pediatric gliomas: from molecular mechanisms to therapeutic implications. 小儿胶质瘤的表观遗传学重编程：从分子机制到治疗意义。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-12-01 Epub Date: 2024-10-10 DOI: 10.1016/j.trecan.2024.09.007
Santiago Haase, Stephen Carney, Maria Luisa Varela, Devarshi Mukherji, Ziwen Zhu, Yingxiang Li, Felipe J Nuñez, Pedro R Lowenstein, Maria G Castro
{"title":"Epigenetic reprogramming in pediatric gliomas: from molecular mechanisms to therapeutic implications.","authors":"Santiago Haase, Stephen Carney, Maria Luisa Varela, Devarshi Mukherji, Ziwen Zhu, Yingxiang Li, Felipe J Nuñez, Pedro R Lowenstein, Maria G Castro","doi":"10.1016/j.trecan.2024.09.007","DOIUrl":"10.1016/j.trecan.2024.09.007","url":null,"abstract":"<p><p>Brain tumors in children and adults differ greatly in patient outcomes and responses to radiotherapy and chemotherapy. Moreover, the prevalence of recurrent mutations in histones and chromatin regulatory proteins in pediatric and young adult gliomas suggests that the chromatin landscape is rewired to support oncogenic programs. These early somatic mutations dysregulate widespread genomic loci by altering the distribution of histone post-translational modifications (PTMs) and, in consequence, causing changes in chromatin accessibility and in the histone code, leading to gene transcriptional changes. We review how distinct chromatin imbalances in glioma subtypes impact on oncogenic features such as cellular fate, proliferation, immune landscape, and radio resistance. Understanding these mechanisms of epigenetic dysregulation carries substantial implications for advancing targeted epigenetic therapies.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1147-1160"},"PeriodicalIF":14.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406950","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}
引用次数: 0
Advances in LAG3 cancer immunotherapeutics. LAG3 癌症免疫疗法的进展。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-11-26 DOI: 10.1016/j.trecan.2024.10.009
Kieran Adam, Samuel C Butler, Creg J Workman, Dario A A Vignali
{"title":"Advances in LAG3 cancer immunotherapeutics.","authors":"Kieran Adam, Samuel C Butler, Creg J Workman, Dario A A Vignali","doi":"10.1016/j.trecan.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.10.009","url":null,"abstract":"<p><p>Cancer treatment has entered the age of immunotherapy. Immune checkpoint inhibitor (ICI) therapy has shown robust therapeutic potential in clinical practice, with significant improvements in progression-free survival (PFS) and overall survival (OS). Recently, checkpoint blockade of the lymphocyte activation gene 3 (LAG3) inhibitory receptor (IR) in combination with programmed death protein 1 (PD1) inhibition has been FDA approved in patients with advanced melanoma. This has encouraged the clinical evaluation of new LAG3-directed biologics in combination with other checkpoint inhibitors. Several of these studies are evaluating bispecific antibodies that target exhausted T (T<sub>EX</sub>) cells expressing multiple IRs. This review discusses the current understanding of LAG3 in regulating antitumor immunity and the ongoing clinical testing of LAG3 inhibition in cancer.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740603","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}
引用次数: 0
Generation of tumor neoantigens by RNA splicing perturbation. 通过 RNA 剪接扰乱生成肿瘤新抗原。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-11-22 DOI: 10.1016/j.trecan.2024.10.008
Adi Rosenberg-Mogilevsky, Zahava Siegfried, Rotem Karni
{"title":"Generation of tumor neoantigens by RNA splicing perturbation.","authors":"Adi Rosenberg-Mogilevsky, Zahava Siegfried, Rotem Karni","doi":"10.1016/j.trecan.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.10.008","url":null,"abstract":"<p><p>Immunotherapy has revolutionized cancer treatment, but the limited availability of tumor-specific neoantigens still remains a challenge. The potential of alternative mRNA splicing-derived neoantigens as a source of new immunotherapy targets has gained significant attention. Tumors exhibit unique splicing changes and splicing factor mutations which are prevalent in various cancers and play a crucial role in neoantigen production. We present advances in splicing modulation approaches, including small-molecule drugs, decoy and splice-switching antisense oligonucleotides (SSOs), CRISPR, small interfering RNAs (siRNAs), and nonsense-mediated RNA decay (NMD) inhibition, that can be adapted to enhance antitumor immune responses. Finally, we explore the clinical implications of these approaches, highlighting their potential to transform cancer immunotherapy and broaden its efficacy.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693709","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}
引用次数: 0
Targeting the Hippo pathway in cancer: kidney toxicity as a class effect of TEAD inhibitors? 以癌症中的希波通路为靶点：肾毒性是 TEAD 抑制剂的一类效应？
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-11-08 DOI: 10.1016/j.trecan.2024.10.004
Sayantanee Paul, Jessica Sims, Trang Pham, Anwesha Dey
{"title":"Targeting the Hippo pathway in cancer: kidney toxicity as a class effect of TEAD inhibitors?","authors":"Sayantanee Paul, Jessica Sims, Trang Pham, Anwesha Dey","doi":"10.1016/j.trecan.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.10.004","url":null,"abstract":"<p><p>The Hippo pathway has emerged as a critical player in both cancers and targeted therapy resistance. Recent drug discovery efforts have led to the development of TEAD inhibitors, several of which have already progressed to the clinic. To truly leverage their potential as anticancer therapeutics, safety considerations, particularly in regard to the kidney, warrant additional investigation. This review explores the Hippo pathway's role in cancers, its therapeutic potential, role in kidney development, and the need to evaluate the best strategies to translate its clinical application for long-term patient benefit.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628777","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}
引用次数: 0
Metabolic landscape of disseminated cancer dormancy. 扩散性癌症休眠的代谢景观
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-11-06 DOI: 10.1016/j.trecan.2024.10.005
Stanislav Drapela, Bruna M Garcia, Ana P Gomes, Ana Luísa Correia
{"title":"Metabolic landscape of disseminated cancer dormancy.","authors":"Stanislav Drapela, Bruna M Garcia, Ana P Gomes, Ana Luísa Correia","doi":"10.1016/j.trecan.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.10.005","url":null,"abstract":"<p><p>Cancer dormancy is a phenomenon defined by the entry of cancer cells into a reversible quiescent, nonproliferative state, and represents an essential part of the metastatic cascade responsible for cancer recurrence and mortality. Emerging evidence suggests that metabolic reprogramming plays a pivotal role in enabling entry, maintenance, and exit from dormancy in the face of the different environments of the metastatic cascade. Here, we review the current literature to understand the dynamics of metabolism during dormancy, highlighting its fine-tuning by the host micro- and macroenvironment, and put forward the importance of identifying metabolic vulnerabilities of the dormant state as therapeutic targets to eradicate recurrent disease.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606455","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}
引用次数: 0
Artificial intelligence improves mammography-based breast cancer risk prediction. 人工智能改进了基于乳房 X 射线照相术的乳腺癌风险预测。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-11-05 DOI: 10.1016/j.trecan.2024.10.007
Wendy V Ingman, Kara L Britt, Jennifer Stone, Tuong L Nguyen, John L Hopper, Erik W Thompson
{"title":"Artificial intelligence improves mammography-based breast cancer risk prediction.","authors":"Wendy V Ingman, Kara L Britt, Jennifer Stone, Tuong L Nguyen, John L Hopper, Erik W Thompson","doi":"10.1016/j.trecan.2024.10.007","DOIUrl":"https://doi.org/10.1016/j.trecan.2024.10.007","url":null,"abstract":"<p><p>Artificial intelligence (AI) is enabling us to delve deeply into the information inherent in a mammogram and identify novel features associated with high risk of a future breast cancer diagnosis. Here, we discuss how AI is improving mammographic density-associated risk prediction and shaping the future of screening and risk-reducing strategies.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822725","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}
引用次数: 0
Epigenetic control of immunoevasion in cancer stem cells. 癌症干细胞免疫逃逸的表观遗传学控制。
IF 14.3 1区 医学
Trends in cancer Pub Date : 2024-11-01 Epub Date: 2024-09-06 DOI: 10.1016/j.trecan.2024.08.004
Claudia Galassi, Manel Esteller, Ilio Vitale, Lorenzo Galluzzi
{"title":"Epigenetic control of immunoevasion in cancer stem cells.","authors":"Claudia Galassi, Manel Esteller, Ilio Vitale, Lorenzo Galluzzi","doi":"10.1016/j.trecan.2024.08.004","DOIUrl":"10.1016/j.trecan.2024.08.004","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are a poorly differentiated population of malignant cells that (at least in some neoplasms) is responsible for tumor progression, resistance to therapy, and disease relapse. According to a widely accepted model, all stages of cancer progression involve the ability of neoplastic cells to evade recognition or elimination by the host immune system. In line with this notion, CSCs are not only able to cope with environmental and therapy-elicited stress better than their more differentiated counterparts but also appear to better evade tumor-targeting immune responses. We summarize epigenetic modifications of DNA and histones through which CSCs evade immune recognition or elimination, and propose that such alterations constitute promising therapeutic targets to increase the sensitivity of some malignancies to immunotherapy.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":"1052-1071"},"PeriodicalIF":14.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146405","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}
引用次数: 0
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