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Structural pharmacology of TRPA1 channel. TRPA1通道的结构药理学。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-08-01 Epub Date: 2026-07-07 DOI: 10.1016/j.tips.2026.06.003
Bethan A Cole, Huifen Chen, Alexis Rohou, Jun Chen
{"title":"Structural pharmacology of TRPA1 channel.","authors":"Bethan A Cole, Huifen Chen, Alexis Rohou, Jun Chen","doi":"10.1016/j.tips.2026.06.003","DOIUrl":"10.1016/j.tips.2026.06.003","url":null,"abstract":"<p><p>Transient receptor potential ankyrin 1 (TRPA1) is a nonselective cation channel predominantly expressed in sensory neurons. Genetic associations of TRPA1 with human diseases, along with extensive experimental evidence, have fueled interest in targeting TRPA1 for the treatment of pain, itch, and respiratory disorders. TRPA1 responds to a remarkably broad spectrum of agonists, including electrophilic and nonelectrophilic natural products, endogenous metabolites, marketed drugs, and synthetic compounds. Numerous antagonists have been identified, several of which have advanced into clinical trials. Recent cryogenic electron microscopy and mutagenesis studies have revealed at least ten distinct ligand-binding sites and modulation mechanisms. In this review, we highlight recent advances in the versatile pharmacology of TRPA1 and its therapeutic development, shaped by both natural and rationally designed modulators.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"906-918"},"PeriodicalIF":24.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405727","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 developmental reprogramming: hPSC insights for cancer interception. 靶向发育重编程：hPSC对癌症拦截的见解。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-08-01 Epub Date: 2026-06-23 DOI: 10.1016/j.tips.2026.05.011
Xiaohui Xu, Xiaolei Dong, Jinyu Li, Yifei Liu, Zheng Wang
{"title":"Targeting developmental reprogramming: hPSC insights for cancer interception.","authors":"Xiaohui Xu, Xiaolei Dong, Jinyu Li, Yifei Liu, Zheng Wang","doi":"10.1016/j.tips.2026.05.011","DOIUrl":"10.1016/j.tips.2026.05.011","url":null,"abstract":"<p><p>Cancer is increasingly conceptualized as a disease of distorted human development, where oncogenic events trigger developmental reprogramming by subverting physiological lineage programs. Conventional cancer models often fail to capture this early transition, as they primarily reflect end-stage tumors or nonhuman biology. Human pluripotent stem cells (hPSCs) circumvent these limitations by enabling the reconstruction of oncogenic events within precisely defined human developmental trajectories. In this review, we examine emerging principles of lineage bias and differentiation arrest revealed by hPSC-derived models across brain, retinal, and myeloid malignancies, as well as hereditary cancer predispositions. Crucially, we discuss how these models reveal therapeutic windows linked to defined developmental states to reverse lineage hijacking, translating developmental insights into pharmacological strategies for early cancer interception.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"840-854"},"PeriodicalIF":24.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148309615","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
Chaperones in kinase homeostasis and drug discovery. 激酶内稳态中的伴侣蛋白和药物发现。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-08-01 Epub Date: 2026-07-09 DOI: 10.1016/j.tips.2026.06.004
Caiyiren Wen, Qidong You, Lei Wang
{"title":"Chaperones in kinase homeostasis and drug discovery.","authors":"Caiyiren Wen, Qidong You, Lei Wang","doi":"10.1016/j.tips.2026.06.004","DOIUrl":"10.1016/j.tips.2026.06.004","url":null,"abstract":"<p><p>Molecular chaperones play a central role in kinase homeostasis by guiding the folding, maturation, and stability of kinase clients. Yet advances in kinase folding and post-translational modification have not been adequately integrated into a coherent chaperone-centered framework, limiting a unified understanding of kinase homeostasis, and constraining more systematic efforts to target the chaperone-kinase axis. Recent structural and mechanistic studies now support a model in which chaperone assemblies function as regulatory platforms that coordinate kinase maturation, modification, and fate control. This review integrates these advances into a chaperone-centered view of kinase homeostasis and discusses pharmacological strategies targeting the chaperone-kinase axis, including chaperone modulation, interface disruption, and bifunctional approaches.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"919-937"},"PeriodicalIF":24.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424306","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
Halting neuron-fibroblast crosstalk disarms tumor and augments immunotherapy. 停止神经元-成纤维细胞串扰解除肿瘤并增强免疫治疗。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-08-01 Epub Date: 2026-05-01 DOI: 10.1016/j.tips.2026.03.006
Pinchao Fan, Xiaofei Zhi, Weici Laurence Liu
{"title":"Halting neuron-fibroblast crosstalk disarms tumor and augments immunotherapy.","authors":"Pinchao Fan, Xiaofei Zhi, Weici Laurence Liu","doi":"10.1016/j.tips.2026.03.006","DOIUrl":"10.1016/j.tips.2026.03.006","url":null,"abstract":"<p><p>Innervation propels tumor progression through intricate mechanisms. Recently, Zhang et al. demonstrated that sensory neurons interact with cancer-associated fibroblasts via the calcitonin gene-related peptide (CGRP)-receptor activity-modifying protein 1 (RAMP1) axis to mediate immune exclusion in triple-negative breast cancer. Halting the neuron-fibroblast crosstalk via rimegepant holds promise for reorganizing the extracellular matrix and synergizing with cancer immunotherapy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"831-834"},"PeriodicalIF":24.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821020","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
Vepdegestrant for ESR1-mutated breast cancer. vepdegestran治疗esr1突变乳腺癌。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-08-01 Epub Date: 2026-07-10 DOI: 10.1016/j.tips.2026.06.009
Ryan S MacLeod, Chuan-Ju Liu
{"title":"Vepdegestrant for ESR1-mutated breast cancer.","authors":"Ryan S MacLeod, Chuan-Ju Liu","doi":"10.1016/j.tips.2026.06.009","DOIUrl":"10.1016/j.tips.2026.06.009","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"940-941"},"PeriodicalIF":24.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13360994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424375","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
Engineering cells for solid tumor therapy. 用于实体瘤治疗的工程细胞。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-08-01 Epub Date: 2026-07-07 DOI: 10.1016/j.tips.2026.06.002
Yuyang Xiao, Yue Wu, Qinyan Cao, Lina Wu, Yanan Li, Guang Yang, He Huang, Lingtong Meng
{"title":"Engineering cells for solid tumor therapy.","authors":"Yuyang Xiao, Yue Wu, Qinyan Cao, Lina Wu, Yanan Li, Guang Yang, He Huang, Lingtong Meng","doi":"10.1016/j.tips.2026.06.002","DOIUrl":"10.1016/j.tips.2026.06.002","url":null,"abstract":"<p><p>Living cell therapy and nonliving drugs are both key approaches for treating solid tumors. Engineering living cells with nonliving drugs harnesses their complementary advantages to enhance therapeutic outcomes. However, inappropriate engineering methods or design strategies can compromise the synergy between cells and drugs. In this review, we provide a decision framework that matches engineering strategies to cell types and drug properties, yielding baseline-qualified engineered cells. To address barriers specific to solid tumors, we then discuss strategies for equipping cells with additional functions that enable deeper penetration, resistance to immunosuppression, and controlled release. We also discuss emerging strategies to increase their safety during clinical translation. This review aims to guide the rational design of next-generation engineered cell therapies to achieve improved clinical outcomes.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"855-870"},"PeriodicalIF":24.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397882","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
Gene therapy for spinocerebellar ataxias. 脊髓小脑共济失调的基因治疗。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-08-01 Epub Date: 2026-07-09 DOI: 10.1016/j.tips.2026.06.008
Hyemi Eo, Eugene Bok, Ho-Won Lee, Kyoungho Suk, Hyung-Jun Kim, Jaekwang Kim, Sang Ryong Kim
{"title":"Gene therapy for spinocerebellar ataxias.","authors":"Hyemi Eo, Eugene Bok, Ho-Won Lee, Kyoungho Suk, Hyung-Jun Kim, Jaekwang Kim, Sang Ryong Kim","doi":"10.1016/j.tips.2026.06.008","DOIUrl":"10.1016/j.tips.2026.06.008","url":null,"abstract":"<p><p>Spinocerebellar ataxias (SCAs), rare neurodegenerative disorders characterized by progressive cerebellar degeneration, cause impaired balance and motor dysfunction. Although most cases are inherited, sporadic forms also occur, and effective disease-modifying therapies remain unavailable despite advances in understanding their genetic and molecular mechanisms. This unmet need is particularly significant because many SCAs are monogenic disorders caused by well-characterized mutations, making them promising candidates for gene- and RNA-based therapies. Recent advances in antisense oligonucleotides, RNA interference, vector engineering, and genome editing have increasingly enabled the alignment of therapeutic strategies with specific mutational architectures. Therefore, this review aims to examine how genetic subclassification informs platform selection, summarize recent advances in gene- and RNA-based therapeutics, and outline key translational barriers to clinical implementation in SCAs.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"871-889"},"PeriodicalIF":24.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412661","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
STING-mediated cancer immunotherapy: emerging modalities and beyond. sting介导的癌症免疫治疗：新兴模式和超越。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-25 DOI: 10.1016/j.tips.2026.07.002
Ramesha Hanumanthappa, Nandakumar Dalavaikodihalli Nanjaiah, Sudhir H Ranganath
{"title":"STING-mediated cancer immunotherapy: emerging modalities and beyond.","authors":"Ramesha Hanumanthappa, Nandakumar Dalavaikodihalli Nanjaiah, Sudhir H Ranganath","doi":"10.1016/j.tips.2026.07.002","DOIUrl":"https://doi.org/10.1016/j.tips.2026.07.002","url":null,"abstract":"<p><p>The clinical translation of stimulator of interferon genes (STING)agonist-based cancer immunotherapy is limited by uncontrolled and sustained STING activation, which leads to immune exhaustion and systemic toxicity. In this forum, we critically analyze recent advances, including stimuli-responsive, biomimetic, pulsatile, intracellular-triggered release, and synergistic systems that enable precise spatiotemporal STING activation, as well as associated gaps in clinical translation. Finally, we present futuristic perspectives on next-generation STING-based cancer immunotherapy strategies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593292","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
Endothelial insulin-like growth factor 1 receptor-targeted vessel normalization potentiates neuroendocrine cancer immunotherapy. 内皮胰岛素样生长因子1受体靶向血管正常化增强神经内分泌癌免疫治疗。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-22 DOI: 10.1016/j.tips.2026.07.001
Weici Laurence Liu, Wenjun Mao
{"title":"Endothelial insulin-like growth factor 1 receptor-targeted vessel normalization potentiates neuroendocrine cancer immunotherapy.","authors":"Weici Laurence Liu, Wenjun Mao","doi":"10.1016/j.tips.2026.07.001","DOIUrl":"https://doi.org/10.1016/j.tips.2026.07.001","url":null,"abstract":"<p><p>Angiogenesis fuels cancer progression, yet its immunomodulatory role in neuroendocrine malignancies remains poorly understood. Recently, Wang et al. identified a blood-brain barrier-like vascular gate that mediates immune exclusion and immunotherapy resistance in small-cell lung cancer. Targeting this barrier with OSI-906 enhances CD8<sup>+</sup> T-cell infiltration and immunotherapy efficacy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563001","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
August 2026 issue first authors. 2026年8月号第一作者。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-21 DOI: 10.1016/j.tips.2026.07.003
Bethan Cole, Tarek Mohamed Abd El-Aziz, Hyemi Eo, Caiyiren Wen, Qingtong Zhou
{"title":"August 2026 issue first authors.","authors":"Bethan Cole, Tarek Mohamed Abd El-Aziz, Hyemi Eo, Caiyiren Wen, Qingtong Zhou","doi":"10.1016/j.tips.2026.07.003","DOIUrl":"https://doi.org/10.1016/j.tips.2026.07.003","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550650","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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