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Optogenetic engineering for precision cancer immunotherapy. 精准癌症免疫治疗的光基因工程。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-10 DOI: 10.1016/j.tips.2025.05.002
Yuepeng Ke, Siyao Liu, Yun Huang, Tien-Hung Lan, Yubin Zhou
{"title":"Optogenetic engineering for precision cancer immunotherapy.","authors":"Yuepeng Ke, Siyao Liu, Yun Huang, Tien-Hung Lan, Yubin Zhou","doi":"10.1016/j.tips.2025.05.002","DOIUrl":"10.1016/j.tips.2025.05.002","url":null,"abstract":"<p><p>Cancer immunotherapy has revolutionized oncology, but its full potential remains constrained by treatment resistance, limited durability, immune evasion, and systemic toxicity. Overcoming these obstacles requires innovative strategies for remote and targeted immunomodulation. Opsin-free optogenetics has emerged as a powerful tool in cancer immunotherapy because its versatility and photoactivation kinetics align with the timescale of immune cell signaling, and it has given rise to the subfield of optogenetic immunoengineering. This review explores design strategies and key applications of optogenetic immunoengineering, focusing on the opsin-free optogenetic toolkit in immunotherapy and its ability to modulate the cancer-immunity cycle which is required for amplifying and sustaining antitumor responses. By enabling precise regulation of both innate and adaptive immunity, as demonstrated in recent preclinical studies, optogenetic immunoengineering holds great promise for advancing next-generation precision medicine.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276004","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 13.9 1区 医学
Trends in pharmacological sciences Pub 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":"https://doi.org/10.1016/j.tips.2025.05.007","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting AMPK as a potential treatment for hepatic fibrosis in MASLD. 靶向AMPK作为MASLD肝纤维化的潜在治疗方法。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-04-28 DOI: 10.1016/j.tips.2025.03.008
Xavier Palomer, Jue-Rui Wang, Claudia Escalona, Siyuan Wu, Walter Wahli, Manuel Vázquez-Carrera
{"title":"Targeting AMPK as a potential treatment for hepatic fibrosis in MASLD.","authors":"Xavier Palomer, Jue-Rui Wang, Claudia Escalona, Siyuan Wu, Walter Wahli, Manuel Vázquez-Carrera","doi":"10.1016/j.tips.2025.03.008","DOIUrl":"10.1016/j.tips.2025.03.008","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, and often progresses to hepatic fibrosis, cirrhosis, and liver failure. Despite its increasing prevalence, effective pharmacological treatments for MASLD-related fibrosis remain limited. Recent research has highlighted AMP-activated protein kinase (AMPK) as a key regulator of the processes that promote fibrogenesis, and AMPK activation shows potential in mitigating fibrosis. Advances in AMPK activators and deeper insights into their role in fibrotic pathways have recently revitalized interest in targeting AMPK for fibrosis treatment. This review discusses the molecular mechanisms linking AMPK to hepatic fibrosis and evaluates emerging AMPK-directed therapies. Furthermore, it addresses challenges in clinical translation. Importantly, we combine the latest mechanistic discoveries with recent therapeutic developments to provide a comprehensive perspective on AMPK as a target for hepatic fibrosis treatment.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"551-566"},"PeriodicalIF":13.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049837","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
Developmental toxicity: artificial intelligence-powered assessments. 发育毒性：人工智能驱动的评估。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-05-15 DOI: 10.1016/j.tips.2025.04.005
Tong Wang, Xuelian Jia, Lauren M Aleksunes, Hui Shen, Hong-Wen Deng, Hao Zhu
{"title":"Developmental toxicity: artificial intelligence-powered assessments.","authors":"Tong Wang, Xuelian Jia, Lauren M Aleksunes, Hui Shen, Hong-Wen Deng, Hao Zhu","doi":"10.1016/j.tips.2025.04.005","DOIUrl":"10.1016/j.tips.2025.04.005","url":null,"abstract":"<p><p>Regulatory agencies require comprehensive toxicity testing for prenatal drug exposure, including new drugs in development, to reduce concerns about developmental toxicity, that is, drug-induced toxicity and adverse effects in pregnant women and fetuses. However, defining developmental toxicity endpoints and optimal analysis of associated public big data remain challenging. Recently, artificial intelligence (AI) approaches have had a critical role in analyzing complex, high-dimensional data, uncovering subtle relationships between chemical exposures and associated developmental risks. Here, we present an overview of major big data resources and data-driven models that focus on predicting various toxicity endpoints. We also highlight emerging, interpretable AI models that integrate multimodal data and domain knowledge to reveal toxic mechanisms underlying complex endpoints, and outline a potential framework that leverages multiple interpretable models to comprehensively evaluate chemical-induced developmental toxicity.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"486-502"},"PeriodicalIF":13.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080572","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
Phylogeny-guided discovery of new antifungals. 系统发育引导下发现新的抗真菌药物。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-05-14 DOI: 10.1016/j.tips.2025.04.004
Nicolas Papon, Vincent Courdavault, Vishnu Chaturvedi
{"title":"Phylogeny-guided discovery of new antifungals.","authors":"Nicolas Papon, Vincent Courdavault, Vishnu Chaturvedi","doi":"10.1016/j.tips.2025.04.004","DOIUrl":"10.1016/j.tips.2025.04.004","url":null,"abstract":"<p><p>Fungal infections are increasing globally, with limited antifungal classes, drug toxicity issues, and the rapid emergence of multidrug resistance (MDR). By using a glycosyltransferase phylogeny-guided strategy, Deng and colleagues recently identified a new broad-spectrum polyene macrolide active against many fungal pathogens, with a novel mechanism of action and excellent safety profile.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"483-485"},"PeriodicalIF":13.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080574","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
Molecular glue meets antibody: next-generation antibody-drug conjugates. 分子胶与抗体结合：新一代抗体-药物偶联物。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-05-08 DOI: 10.1016/j.tips.2025.04.002
Yiran Tao, Ying Lu, Bin Yu, Yuxi Wang
{"title":"Molecular glue meets antibody: next-generation antibody-drug conjugates.","authors":"Yiran Tao, Ying Lu, Bin Yu, Yuxi Wang","doi":"10.1016/j.tips.2025.04.002","DOIUrl":"10.1016/j.tips.2025.04.002","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have revolutionized oncology by enabling the delivery of cytotoxic agents. However, persistent limitations in payload diversity and emerging drug-resistance mechanisms have spurred investigations into innovative payload modalities. Molecular glue-antibody conjugates (MACs), which utilize molecular glues as payloads, represent a groundbreaking advance in this field. By leveraging the catalytic, event-driven nature of molecular glues, MACs offer enhanced efficacy, reduced off-target effects, and an improved therapeutic index. Two MACs are now in clinical trials. This review explores MAC mechanisms, advances, and potential to surpass traditional ADCs and molecular glues, while addressing development challenges and future directions.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"520-534"},"PeriodicalIF":13.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987953","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 NLRP3 inflammasome for inflammatory disease therapy. 靶向NLRP3炎性小体用于炎性疾病治疗。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-05-15 DOI: 10.1016/j.tips.2025.04.007
Julia Elise Cabral, Anna Wu, Haitian Zhou, Minh Anh Pham, Sophia Lin, Reginald McNulty
{"title":"Targeting the NLRP3 inflammasome for inflammatory disease therapy.","authors":"Julia Elise Cabral, Anna Wu, Haitian Zhou, Minh Anh Pham, Sophia Lin, Reginald McNulty","doi":"10.1016/j.tips.2025.04.007","DOIUrl":"10.1016/j.tips.2025.04.007","url":null,"abstract":"<p><p>The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is a megadalton complex implicated in numerous inflammation-driven diseases including COVID-19, Alzheimer's disease, and gout. Although past efforts have focused on inhibiting IL-1β downstream of NLRP3 activation using drugs such as canakinumab, no FDA-approved NLRP3-targeted inhibitors are currently available. MCC950, a direct NLRP3 inhibitor, showed promise but exhibited off-target effects. Recent research has focused on optimizing the sulfonylurea-based MCC950 scaffold by leveraging recent structural and medicinal chemistry insights into the NLRP3 nucleotide-binding and oligomerization (NACHT) domain to improve solubility and clinical efficacy. In addition, oxidized DNA (oxDNA) has emerged as a key inflammasome trigger, and molecules targeting the pyrin domain have shown promise in inhibiting NLRP3 activation. This review discusses the role of NLRP3 in inflammation-related diseases, the status of ongoing clinical trials, and emerging small-molecule therapeutics targeting NLRP3.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"503-519"},"PeriodicalIF":13.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080576","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 frameshifting element in coronaviruses: structure, function, and potential as a therapeutic target. 冠状病毒中的移框元件：结构、功能和作为治疗靶点的潜力
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-05-16 DOI: 10.1016/j.tips.2025.04.003
Qi Li, Qian Wang, Rui Wang, Liangren Zhang, Zhenming Liu
{"title":"The frameshifting element in coronaviruses: structure, function, and potential as a therapeutic target.","authors":"Qi Li, Qian Wang, Rui Wang, Liangren Zhang, Zhenming Liu","doi":"10.1016/j.tips.2025.04.003","DOIUrl":"10.1016/j.tips.2025.04.003","url":null,"abstract":"<p><p>The frameshifting element (FSE) comprises a slippery heptanucleotide sequence followed by a downstream RNA structure, such as a pseudoknot or stem-loop. Found in various RNA viruses, FSE regulates viral replication via programmed -1 ribosomal frameshifting (-1 PRF), making it a potential broad-spectrum antiviral target. Advances in RNA structural analysis have elucidated the dynamic conformations and cross-viral diversity of FSE, with the SARS-CoV-2 outbreak further highlighting its role in viral replication. Efforts to develop antiviral drugs targeting FSE have progressed through virtual and phenotypic screening. In this review, we explore the evolution, structure, and function of FSE in coronaviruses, evaluate recent advances in FSE-targeted drug development, and discuss their design advantages, efficacy, and challenges, providing insights for future antiviral strategies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"535-550"},"PeriodicalIF":13.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094942","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
Afamitresgene autoleucel: first cell therapy for synovial sarcoma. 阿米米雷斯基因自体甲醇：滑膜肉瘤的第一细胞疗法。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-03-27 DOI: 10.1016/j.tips.2025.03.002
Soumyajit Das, Sandro Matosevic
{"title":"Afamitresgene autoleucel: first cell therapy for synovial sarcoma.","authors":"Soumyajit Das, Sandro Matosevic","doi":"10.1016/j.tips.2025.03.002","DOIUrl":"10.1016/j.tips.2025.03.002","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"584-585"},"PeriodicalIF":13.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742580","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
Sotatercept in pulmonary arterial hypertension. 索特塞普治疗肺动脉高压。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-16 DOI: 10.1016/j.tips.2025.04.008
Jean-Luc Cracowski, Charles Khouri
{"title":"Sotatercept in pulmonary arterial hypertension.","authors":"Jean-Luc Cracowski, Charles Khouri","doi":"10.1016/j.tips.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.tips.2025.04.008","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094870","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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