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Targeting glycosylation to enhance tumor immunotherapy. 靶向糖基化增强肿瘤免疫治疗。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-09-01 Epub Date: 2025-08-14 DOI: 10.1016/j.tips.2025.07.013
Qiang Zhu, Xiaoming Chen, Xiaotao Duan, Jianwei Sun, Wen Yi
{"title":"Targeting glycosylation to enhance tumor immunotherapy.","authors":"Qiang Zhu, Xiaoming Chen, Xiaotao Duan, Jianwei Sun, Wen Yi","doi":"10.1016/j.tips.2025.07.013","DOIUrl":"10.1016/j.tips.2025.07.013","url":null,"abstract":"<p><p>Glycans are complex sugar modifications found on cell surfaces that play crucial roles in biological processes. Glycosylation patterns are aberrantly altered in the tumor microenvironment (TME), which helps cancer cells escape immune surveillance by creating a tumor-specific 'glyco-code' that weakens immune responses and reduces immunotherapy effectiveness. Recent studies have illustrated the potential to improve antitumor immune responses by manipulating glycosylation in the TME. We review the effects of aberrant glycosylation on the regulation of tumor immunity and the corresponding strategies for manipulating glycosylation to enhance antitumor immunity. These strategies include inhibiting glycan-receptor interactions, engineering cell-surface glycans, and remodeling the extracellular matrix. This Review highlights the importance of glycosylation in designing effective and personalized cancer treatments.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"863-876"},"PeriodicalIF":19.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859645","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
Cardiac fibrosis: from mechanisms and models to medicines. 心脏纤维化：从机制、模型到药物。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-27 DOI: 10.1016/j.tips.2025.07.016
Wenqiang Liu, Xuekun Wu, Wenshu Zeng, Mark Chandy, Joseph C Wu
{"title":"Cardiac fibrosis: from mechanisms and models to medicines.","authors":"Wenqiang Liu, Xuekun Wu, Wenshu Zeng, Mark Chandy, Joseph C Wu","doi":"10.1016/j.tips.2025.07.016","DOIUrl":"https://doi.org/10.1016/j.tips.2025.07.016","url":null,"abstract":"<p><p>Cardiac fibrosis is a hallmark of cardiovascular and systemic diseases that arises in diverse pathological contexts such as inflammation, metabolic stress, and mechanical overload. Despite its clinical relevance, no FDA-approved therapies directly target cardiac fibrotic remodeling, highlighting persistent challenges in disease organization, model fidelity, and translational strategy. Recent advances in human induced pluripotent stem cell (iPSC)-derived models, engineered heart tissues, and in vivo systems have uncovered new fibrotic drivers, including immune-stroma crosstalk, metabolic reprogramming, and mechanotransduction, that are reshaping therapeutic development. This review synthesizes emerging molecular mechanisms, experimental models, and preclinical and clinical investigations of antifibrotic agents. Distinct from previous reviews, we emphasize cross-contextual alignment to support the development of precision antifibrotic therapy for cardiac fibrosis.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":19.9,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970385","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
The ABCs of psychedelics: a preclinical roadmap for drug discovery. 迷幻药的基础知识：药物发现的临床前路线图。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-27 DOI: 10.1016/j.tips.2025.07.017
Alex C Kwan, John R Mantsch, John D McCorvy
{"title":"The ABCs of psychedelics: a preclinical roadmap for drug discovery.","authors":"Alex C Kwan, John R Mantsch, John D McCorvy","doi":"10.1016/j.tips.2025.07.017","DOIUrl":"10.1016/j.tips.2025.07.017","url":null,"abstract":"<p><p>There is growing interest in developing psychedelic-inspired drugs for treating psychiatric disorders. However, identifying next-generation psychedelic analogs with ideal receptor selectivity and true therapeutic efficacy remains a major challenge. Recent progress has been driven by advances in determining agonist-induced biased signal transduction, high-content behavioral phenotyping via automated video analysis, drug-evoked structural neural remodeling, and activity-dependent gene expression. In this review, we outline a framework for evaluating psychedelics and non-hallucinogenic serotonin 2A (5-HT<sub>2A</sub>) receptor agonists. We critically examine current methods for assessing (A) agonism, (B) behavior, and (C) cellular plasticity. We highlight emerging techniques that may improve translation to humans. We contend that an effective discovery pipeline must align with specific experimental goals and incorporate multiple approaches to be successful for psychedelic drug development.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":19.9,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970539","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
Beyond lipids: fenofibrate in diabetic retinopathy and nephropathy. 非诺贝特治疗糖尿病视网膜病变和肾病。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-19 DOI: 10.1016/j.tips.2025.07.014
Mengying Liu, Seok Ting Lim, Weihua Song, Thomas M Coffman, Xiaomeng Wang
{"title":"Beyond lipids: fenofibrate in diabetic retinopathy and nephropathy.","authors":"Mengying Liu, Seok Ting Lim, Weihua Song, Thomas M Coffman, Xiaomeng Wang","doi":"10.1016/j.tips.2025.07.014","DOIUrl":"https://doi.org/10.1016/j.tips.2025.07.014","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) and nephropathy (DN) are leading microvascular complications of diabetes, yet current therapies remain inadequate. Fenofibrate, a peroxisome proliferator-activated receptor (PPAR)-α agonist approved for dyslipidemia, has gained attention for its protective effects on the retina and kidney that extend beyond lipid modulation. Emerging preclinical and clinical evidence highlights the pleiotropic actions of fenofibrate (anti-inflammatory, antioxidative, neuroprotective, and antifibrotic), mediated through both PPAR-α-dependent and -independent pathways. These properties support its potential benefits in DR and DN, even in normolipidemic individuals. In this review, we integrate mechanistic insights with clinical outcomes, critically evaluate landmark trials, and explore emerging molecular targets of fenofibrate. We highlight the multifunctional actions of fenofibrate and propose strategies to advance its clinical utility in diabetic microvascular complications.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":19.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970397","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
18F-Flurpiridaz PET for imaging of myocardial ischemia. 18f -氟吡唑PET用于心肌缺血显像。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-13 DOI: 10.1016/j.tips.2025.07.011
Taoqian Zhao, Achi Haider, Steven H Liang
{"title":"<sup>18</sup>F-Flurpiridaz PET for imaging of myocardial ischemia.","authors":"Taoqian Zhao, Achi Haider, Steven H Liang","doi":"10.1016/j.tips.2025.07.011","DOIUrl":"https://doi.org/10.1016/j.tips.2025.07.011","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":19.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856432","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 LKB1/STK11-mutant cancer: distinct metabolism, microenvironment, and therapeutic resistance. 靶向LKB1/ stk11突变型癌症：不同的代谢、微环境和治疗耐药性
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-07-22 DOI: 10.1016/j.tips.2025.06.008
Allegra C Minor, Evan Couser, Lillian J Eichner
{"title":"Targeting LKB1/STK11-mutant cancer: distinct metabolism, microenvironment, and therapeutic resistance.","authors":"Allegra C Minor, Evan Couser, Lillian J Eichner","doi":"10.1016/j.tips.2025.06.008","DOIUrl":"10.1016/j.tips.2025.06.008","url":null,"abstract":"<p><p>Despite the development of new classes of therapeutics in oncology, patients with tumors harboring mutations in the tumor suppressor gene STK11/LKB1 continue to exhibit poor clinical response and therapeutic resistance. Recent advances in the understanding of LKB1-mutant tumor biology have illuminated how metabolism and the tumor microenvironment (TME) function as effectors of the aggressive nature of this tumor type. New findings have revealed how metabolic reprogramming, a hallmark of LKB1-mutant tumor biology, can be exploited as a potential targetable liability in these tumors. Characterization of the distinctly immunosuppressive LKB1-mutant TME has motivated multiple discoveries of new approaches for rewiring the microenvironment to overcome immunotherapy resistance. Indeed, overcoming therapeutic resistance in LKB1-deficient tumors continues to be a major research focus, and some preclinical studies have advanced to clinical trials. In this review, we critically analyze these findings and discuss therapies in development that aim to leverage this new understanding for clinical benefit.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"722-737"},"PeriodicalIF":19.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699640","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
TREM2 and LAG-3 in cancer and Alzheimer's disease immunotherapy. TREM2和LAG-3在癌症和阿尔茨海默病免疫治疗中的作用。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-07-18 DOI: 10.1016/j.tips.2025.06.010
Shaoren Yuan, Natalie S Fuchs, Somaya A Abdel-Rahman, Baljit Kaur, Moustafa T Gabr
{"title":"TREM2 and LAG-3 in cancer and Alzheimer's disease immunotherapy.","authors":"Shaoren Yuan, Natalie S Fuchs, Somaya A Abdel-Rahman, Baljit Kaur, Moustafa T Gabr","doi":"10.1016/j.tips.2025.06.010","DOIUrl":"10.1016/j.tips.2025.06.010","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and cancer are immune-mediated disorders characterized by chronic neuroinflammation and immune evasion, respectively. Recent studies implicate two key immune regulators in both diseases: LAG-3, an adaptive immune checkpoint receptor, and TREM2, an innate receptor expressed on microglia and tumor-associated macrophages (TAMs). LAG-3 inhibitors have demonstrated clinical efficacy in cancer and are being explored in AD research. TREM2 activation supports microglial function in AD, while its inhibition may counteract immunosuppressive macrophages in cancer. In this review we compare the roles, mechanisms, and therapeutic strategies targeting LAG-3 and TREM2 in both diseases. We highlight their distinct immune compartmentalization and the importance of context-specific modulation. Strategies include LAG-3 blockade in cancer and AD, and TREM2 agonism or antagonism depending on disease context. We discuss a framework integrating immune compartment, disease state, and therapeutic modality to guide cross-domain immunotherapy development in cancer and AD.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"738-751"},"PeriodicalIF":19.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668588","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
Structure-function-guided drug development efforts to target lncRNAs. 以lncrna为靶点的结构-功能导向药物开发工作。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-07-31 DOI: 10.1016/j.tips.2025.06.007
Hollie Watmuff, Amy Crawford, Bryan Eusse, Alisha N Jones
{"title":"Structure-function-guided drug development efforts to target lncRNAs.","authors":"Hollie Watmuff, Amy Crawford, Bryan Eusse, Alisha N Jones","doi":"10.1016/j.tips.2025.06.007","DOIUrl":"10.1016/j.tips.2025.06.007","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) play a pivotal role in regulating cellular processes, and their dysregulation has been linked to the progression of disease. Understanding the structural characteristics, protein interactions, and expression dynamics of lncRNAs is essential for deciphering their functional mechanisms. Recent advancements in structural probing techniques have unveiled critical structural motifs and RNA-protein interfaces that contribute to lncRNA dysfunction. Furthermore, developing small molecules, antisense oligonucleotides, and peptidomimetic-based therapeutic agents that target these motifs and interfaces presents promising strategies for treating lncRNA-mediated diseases. This review provides fresh insights into how lncRNAs contribute to disease pathogenesis, focusing on well-characterized lncRNAs, including MALAT1, HOTAIR, GAS5, NEAT1, and XIST as case studies, and explores potential therapeutic agents targeting these lncRNAs to support future drug development efforts.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"703-721"},"PeriodicalIF":19.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761438","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
Design and development of glucocorticoid receptor modulators. 糖皮质激素受体调节剂的设计与研制。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-07-18 DOI: 10.1016/j.tips.2025.06.005
Frank Buttgereit, Christian Elling, Florian Jakob
{"title":"Design and development of glucocorticoid receptor modulators.","authors":"Frank Buttgereit, Christian Elling, Florian Jakob","doi":"10.1016/j.tips.2025.06.005","DOIUrl":"10.1016/j.tips.2025.06.005","url":null,"abstract":"<p><p>Synthetic glucocorticoids (GCs) are effective anti-inflammatory drugs but cause serious adverse effects (AEs). Initially, anti-inflammatory efficacy and AEs were ascribed to GC receptor (GR)-mediated gene transrepression and transactivation, respectively. Although current evidence indicates greater mechanistic complexity of GC action, this proposed distinction in GR-mediated effects has led to the design of novel steroidal and nonsteroidal GR modulators (GRMs) using emerging technologies and new laboratory assays to reduce the AEs associated with synthetic GCs. These GRMs alter the balance between GR transrepression and transactivation. A novel GRM, the dissociated steroid vamorolone, received marketing approval in 2024, confirming that altering the transrepression-transactivation profile is a valid strategy. Here, we review GR-mediated gene regulation and the transrepression-transactivation profile of GCs in relation to their anti-inflammatory efficacy and AEs. We highlight technological advances driving the design/development of novel GRMs, such as selective GR agonists and modulators (SEGRAMs), and provide insights into their mechanism of action.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"771-791"},"PeriodicalIF":19.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668576","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
The ASO drug olezarsen targets familial chylomicronemia syndrome. ASO药物olezarsen针对家族性乳糜微粒血症综合征。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-06-05 DOI: 10.1016/j.tips.2025.05.007
Jing Jin, Le Tra Giang Nguyen, Sherouk M Tawfik, Beshoy Armanios, Xiao-Bo Zhong
{"title":"The ASO drug olezarsen targets familial chylomicronemia syndrome.","authors":"Jing Jin, Le Tra Giang Nguyen, Sherouk M Tawfik, Beshoy Armanios, Xiao-Bo Zhong","doi":"10.1016/j.tips.2025.05.007","DOIUrl":"10.1016/j.tips.2025.05.007","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"814-815"},"PeriodicalIF":19.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249715","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
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