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The B7-H3 (CD276) pathway: emerging biology and clinical therapeutics. B7-H3 （CD276）通路：新兴生物学和临床治疗
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-10-01 Epub Date: 2025-09-12 DOI: 10.1016/j.tips.2025.08.008
Devin T Corrigan, Ankit Tanwar, Meirong Du, Allison M Martin, Xingxing Zang
{"title":"The B7-H3 (CD276) pathway: emerging biology and clinical therapeutics.","authors":"Devin T Corrigan, Ankit Tanwar, Meirong Du, Allison M Martin, Xingxing Zang","doi":"10.1016/j.tips.2025.08.008","DOIUrl":"10.1016/j.tips.2025.08.008","url":null,"abstract":"<p><p>B7-H3 (CD276), an orphan member of the B7 family, is an immune checkpoint ligand and a tumor-associated antigen. Recent developments regarding dimerization, glycosylation, expression regulation, and effects on cell metabolism are emerging, along with a newfound role as a regulator of obesity. As a therapeutic target, ongoing clinical trials with antibody-drug conjugates (ADCs) and chimeric antigen receptor (CAR) immune cells targeting B7-H3 have proved to be safe and effective across different human cancer types. Multiple new preclinical studies have also provided novel treatments targeting B7-H3, including TMIGD2 optimized potent/persistent (TOP) CAR cells, bispecific ADCs, CAR-natural killer (NK) cells, and T cell engagers. In this review we highlight the diverse emerging functions of B7-H3 in both physiological and pathological conditions, and discuss new therapies targeting this molecule.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"975-988"},"PeriodicalIF":19.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058696","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
Reprogramming SUMO-primed ubiquitylation: opportunities in oncology and neurology. sumo引物泛素化的重编程：肿瘤学和神经学的机会。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-10-01 DOI: 10.1016/j.tips.2025.09.002
Gina Gotthardt, Jan Keiten-Schmitz, Stefan Müller
{"title":"Reprogramming SUMO-primed ubiquitylation: opportunities in oncology and neurology.","authors":"Gina Gotthardt, Jan Keiten-Schmitz, Stefan Müller","doi":"10.1016/j.tips.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.tips.2025.09.002","url":null,"abstract":"<p><p>Drugs that reprogram the cellular ubiquitin-proteasome system for removal of disease-causing proteins hold great promise as a new type of pharmacology. Small ubiquitin-related modifier (SUMO)-targeted ubiquitin ligases (StUbLs) are E3 ubiquitin ligases that mediate ubiquitylation of proteins primed by modification with SUMO. The antineoplastic drugs arsenic trioxide and fulvestrant stand out as examples for leveraging a SUMOylation-ubiquitylation cascade to inactivate the oncogenic fusion proteins PML-RARα and estrogen receptor α, respectively. However, approaches harnessing the StUbL system for targeting a broader spectrum of disease-relevant proteins are missing. Recent proof-of-concept studies indicate that proximity-inducing modalities can recruit aggregation-prone proteins to the StUbL machinery, potentially mitigating the formation of neurotoxic inclusions. We review new insights on StUbL-based therapeutics and reflect perspectives of reprogramming SUMO-StUbL signaling for use in oncology and neurology.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":19.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213789","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
Danicopan: complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria. 达尼可潘：补体因子D抑制剂治疗阵发性夜间血红蛋白尿。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-10-01 Epub Date: 2025-08-15 DOI: 10.1016/j.tips.2025.07.007
Ekaterina Umnyakova, Alexander J Lander, Daniel Ricklin
{"title":"Danicopan: complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria.","authors":"Ekaterina Umnyakova, Alexander J Lander, Daniel Ricklin","doi":"10.1016/j.tips.2025.07.007","DOIUrl":"10.1016/j.tips.2025.07.007","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1038-1039"},"PeriodicalIF":19.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859644","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
Potentiation of GPCR signaling by ATP and sugar monophosphates. ATP和单磷酸糖对GPCR信号的增强作用。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-10-01 Epub Date: 2025-08-15 DOI: 10.1016/j.tips.2025.08.002
Sam R J Hoare
{"title":"Potentiation of GPCR signaling by ATP and sugar monophosphates.","authors":"Sam R J Hoare","doi":"10.1016/j.tips.2025.08.002","DOIUrl":"10.1016/j.tips.2025.08.002","url":null,"abstract":"<p><p>Allosteric potentiation of G protein-coupled receptor (GPCR) signaling provides new opportunities for therapeutic discovery. Recently, the laboratory of Peter Chidiac has reported strong allosteric potentiation of numerous GPCRs by extracellular ATP, with the minimal pharmacophore represented by sugar monophosphates. This discovery potentially aids the development of novel allosteric modulators for numerous therapeutically attractive GPCRs.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"925-927"},"PeriodicalIF":19.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862487","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
Viral evasion of cGAS-STING pathway: opportunities for intervention. 病毒逃避cGAS-STING途径：干预的机会
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-10-01 Epub Date: 2025-09-13 DOI: 10.1016/j.tips.2025.08.009
Xiao-Fang Yu, Songdi Wang, Runxin Ye, Wei Wei
{"title":"Viral evasion of cGAS-STING pathway: opportunities for intervention.","authors":"Xiao-Fang Yu, Songdi Wang, Runxin Ye, Wei Wei","doi":"10.1016/j.tips.2025.08.009","DOIUrl":"10.1016/j.tips.2025.08.009","url":null,"abstract":"<p><p>The cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) pathway, a crucial component of host innate immunity, detects aberrant DNA during viral infection. It is well established that cGAS-STING signaling activation during viral infections is often insufficient for complete viral clearance, indicating that numerous viruses have evolved countermeasures against this major pathway. However, the precise mechanisms by which viruses antagonize the cGAS-STING pathway to ensure intracellular survival remain incompletely understood. This review synthesizes recent progress in elucidating how diverse RNA and DNA viruses disrupt various stages of cGAS-STING pathway activation. These mechanistic insights into viral evasion have significant implications for the development of targeted therapeutic interventions. Specifically, the precise delivery of small-molecule or peptide-based drugs designed to counteract viral evasion proteins represents a promising direction for future antiviral therapy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"989-1003"},"PeriodicalIF":19.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065423","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
Multivalent decoy receptor therapeutics to combat viral pandemics and evolution. 对抗病毒大流行和进化的多价诱饵受体疗法。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-10-01 Epub Date: 2025-09-17 DOI: 10.1016/j.tips.2025.08.010
Alex Odoom, Eugene M Obeng, Christian K O Dzuvor
{"title":"Multivalent decoy receptor therapeutics to combat viral pandemics and evolution.","authors":"Alex Odoom, Eugene M Obeng, Christian K O Dzuvor","doi":"10.1016/j.tips.2025.08.010","DOIUrl":"10.1016/j.tips.2025.08.010","url":null,"abstract":"<p><p>Viruses are likely to cause future pandemics due to their inherent ability to evolve and spread rapidly, with limited treatment options. Engineered multivalent decoy receptors (EMDRs) offer a broad-spectrum alternative treatment option. We propose and evaluate EMDRs and their delivery methods to guide future efforts toward pandemic preparedness.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"935-939"},"PeriodicalIF":19.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087492","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
Bimetallic nanoadjuvants for cancer vaccines. 用于癌症疫苗的双金属纳米佐剂
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-10-01 Epub Date: 2025-09-18 DOI: 10.1016/j.tips.2025.08.007
Jiangqi Luo, Yue Wang, Chengzhong Yu, Yannan Yang
{"title":"Bimetallic nanoadjuvants for cancer vaccines.","authors":"Jiangqi Luo, Yue Wang, Chengzhong Yu, Yannan Yang","doi":"10.1016/j.tips.2025.08.007","DOIUrl":"10.1016/j.tips.2025.08.007","url":null,"abstract":"<p><p>Adjuvants are substances used in vaccines to boost antigen-specific immune responses. Aluminum salts (alum) were the first adjuvant approved for human use. Unfortunately, they mainly induce antibody responses and are ineffective at eliciting strong T cell immunity, limiting their use in cancer vaccines. Recent advances reveal the mechanisms of various metal ions in modulating immune signaling. By integrating the synergistic immunomodulation of metal ion pairings with nanotechnology, bimetallic nanoadjuvants (BMNAs) are revolutionizing cancer vaccine. This approach overcomes the limitation of conventional single metal adjuvants by enabling multiplexed immune activation, leading to robust T cell responses for tumor control. This review highlights the immunological mechanisms of metal ions, the rationale behind their pairing in BMNAs, and current challenges for clinical translation.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"958-974"},"PeriodicalIF":19.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092525","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
Non-muscle myosin II is a promising therapeutic target. 非肌球蛋白II是一个很有前景的治疗靶点。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-10-01 Epub Date: 2025-09-12 DOI: 10.1016/j.tips.2025.08.011
Courtney A Miller, Alfredo Quinones-Hinojosa, Steven S Rosenfeld
{"title":"Non-muscle myosin II is a promising therapeutic target.","authors":"Courtney A Miller, Alfredo Quinones-Hinojosa, Steven S Rosenfeld","doi":"10.1016/j.tips.2025.08.011","DOIUrl":"10.1016/j.tips.2025.08.011","url":null,"abstract":"<p><p>Non-muscle myosin II (NMII) comprises a family of cytoplasmic motors with important roles in both normal biology and disease. In this forum article we describe recent developments that validate NMII as a therapeutic target, and we illustrate how this validation can identify novel and translationally viable approaches to treat a variety of diseases.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"931-934"},"PeriodicalIF":19.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055901","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
Multitargeting neuroimmune pathways: novel candidates for chronic pain relief. 多靶点神经免疫通路：缓解慢性疼痛的新候选药物。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-10-01 Epub Date: 2025-09-03 DOI: 10.1016/j.tips.2025.08.005
María Florencia Coronel, Marcelo José Villar, Pablo Rodolfo Brumovsky
{"title":"Multitargeting neuroimmune pathways: novel candidates for chronic pain relief.","authors":"María Florencia Coronel, Marcelo José Villar, Pablo Rodolfo Brumovsky","doi":"10.1016/j.tips.2025.08.005","DOIUrl":"10.1016/j.tips.2025.08.005","url":null,"abstract":"<p><p>Chronic pain remains inadequately managed, partly because of insufficient consideration of neuroimmune interactions in therapeutic design and a continued reliance on single-target strategies ill-suited to its complexity. Multitarget-directed ligands that modulate the non-neuronal microenvironment of neuronal pain pathways show promise, supported by encouraging preclinical data and initial clinical findings.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"940-945"},"PeriodicalIF":19.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001133","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
Optogenetic engineering for precision cancer immunotherapy. 精准癌症免疫治疗的光基因工程。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-10-01 Epub 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":"1018-1037"},"PeriodicalIF":19.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362834/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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