Expert Opinion on Therapeutic Targets最新文献_第6页

Therapeutic activation of the endocannabinoid system for opioid use disorder, chronic pain, and cancer-related pain: a review of current evidence. 内源性大麻素系统激活治疗阿片类药物使用障碍和疼痛的潜力。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-06-01 Epub Date: 2026-06-19 DOI: 10.1080/14728222.2026.2690138

Oluseun Dairo, Jocelyn A Mitchell-Williams, Ping Zhang

{"title":"Therapeutic activation of the endocannabinoid system for opioid use disorder, chronic pain, and cancer-related pain: a review of current evidence.","authors":"Oluseun Dairo, Jocelyn A Mitchell-Williams, Ping Zhang","doi":"10.1080/14728222.2026.2690138","DOIUrl":"10.1080/14728222.2026.2690138","url":null,"abstract":"Introduction: Opioid use disorder (OUD) and chronic pain are major global health challenges. Although opioid therapies provide effective analgesia, long-term use is limited by safety concerns, dependence, and variable efficacy. Modulation of the endocannabinoid system (ECS) has emerged as a potential therapeutic strategy for pain management and opioid-related disorders.Areas covered: This narrative review summarizes evidence on ECS-targeted interventions for OUD, chronic non-cancer pain, and cancer-related pain. Relevant literature was identified through PubMed using terms related to the ECS, cannabinoid receptors (CB1 and CB2), phytocannabinoids (Δ⁹-tetrahydrocannabinol [THC] and cannabidiol [CBD]), synthetic cannabinoids, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibitors, and opioid-cannabinoid interactions. Emphasis is placed on interactions between ECS and opioid signaling pathways and findings from preclinical and clinical studies evaluating efficacy and safety.Expert opinion: This narrative review summarizes evidence on ECS-targeted interventions for OUD, chronic non-cancer pain, and cancer-related pain. Relevant literature was identified through PubMed using terms related to the ECS, cannabinoid receptors (CB1 and CB2), phytocannabinoids (Δ⁹-tetrahydrocannabinol [THC] and cannabidiol [CBD]), synthetic cannabinoids, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibitors, and opioid-cannabinoid interactions. Emphasis is placed on interactions between ECS and opioid signaling pathways and findings from preclinical and clinical studies evaluating efficacy and safety.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"599-610"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

From supportive to targeted treatment strategies: the changing landscape of therapeutics in Alagille syndrome. 从支持到有针对性的治疗策略：阿拉吉尔综合征治疗方法的变化。

IF 4.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-05-01 Epub Date: 2026-05-18 DOI: 10.1080/14728222.2026.2671676

Kavitha Anbarasu, Melissa A Gilbert, Kathleen M Loomes

引用次数: 0

Targets of senescence in cardiac muscle: insights for regenerative treatments in the aged heart. 心肌衰老的目标：对老年心脏再生治疗的见解。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-05-01 Epub Date: 2026-05-17 DOI: 10.1080/14728222.2026.2671690

Georgina M Ellison-Hughes, Daniele Torella

{"title":"Targets of senescence in cardiac muscle: insights for regenerative treatments in the aged heart.","authors":"Georgina M Ellison-Hughes, Daniele Torella","doi":"10.1080/14728222.2026.2671690","DOIUrl":"10.1080/14728222.2026.2671690","url":null,"abstract":"Introduction: Despite considerable investment of time and funding, advancement in cardiac regenerative therapies has been slow. Results of large animal and human studies have failed to live up to the expectations of the positive pre-clinical animal studies. There are many reasons to explain the discrepancies, however a key factor is that patients in need of regenerative therapies are mostly aged, being 70 years and older.Areas covered: The aging heart undergoes structural and functional changes due to biological mechanisms associated with aging. Of these, increased senescent cell burden, inflammaging, and metabolic dysfunction are particularly relevant to the heart. Targeting of senescent cells using senotherapeutics alleviates the detrimental features of cardiac aging, including myocardial dysfunction, hypertrophy and fibrosis, and activates endogenous cardiac regeneration.Expert opinion: The future of myocardial regenerative therapies relies on us dissecting the pathways that regulate the phenotype of the aged heart. Whether these therapies are gene, cell or pharmacological, they must be tested in pre-clinical models and experimental medicine studies which reflect the patient population they are designed to treat. Senotherapeutics hold enormous promise as adjuncts to regenerative therapies by rejuvenating the tissue microenvironment and enhancing the resilience of the aging heart.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"429-436"},"PeriodicalIF":5.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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-level host-microbe interactions: mechanisms, molecules, and modeling toward precision probiotics. 分子水平的宿主-微生物相互作用：机制、分子和精确益生菌的建模。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-05-01 Epub Date: 2026-05-15 DOI: 10.1080/14728222.2026.2671689

Huan Zhang, Shiqi Zhang, Jiangjiang Zhu

{"title":"Molecular-level host-microbe interactions: mechanisms, molecules, and modeling toward precision probiotics.","authors":"Huan Zhang, Shiqi Zhang, Jiangjiang Zhu","doi":"10.1080/14728222.2026.2671689","DOIUrl":"10.1080/14728222.2026.2671689","url":null,"abstract":"Introduction: Advancing next-generation probiotics (NGPs) as precision therapeutics depends on a detailed understanding of host-microbe molecular interactions, as these organisms exert targeted effects through defined bioactive molecules rather than broad, nonspecific mechanisms. This review addresses the need to systematically organize emerging knowledge on microbe-derived molecules (MDMs) that underpin NGP efficacy.Areas covered: This narrative review summarizes recent discoveries of MDMs isolated from NGPs and classifies them based on three principal molecular interaction interfaces: protein-protein/peptide, protein-lipid or glycoconjugates, and protein-metabolite interactions. We discuss how these molecules-encompassing proteins/peptides, lipids, glycoconjugates, and small metabolites-modulate host immune and metabolic pathways to maintain homeostasis. The literature was identified through targeted searches of recent peer-reviewed studies focusing on host-microbe molecular mechanisms and probiotic-derived bioactives. We also review the application of molecular docking, molecular dynamics simulations, and artificial intelligence-based tools in predicting host-interactions and accelerating therapeutic discovery.Expert opinion: By integrating experimental insights with computational strategies, we propose a framework to guide the development of precision microbiome-based interventions tailored to specific diseases and individual microbiome profiles. These advances lay the foundation for rational design of targeted NGP therapies for metabolic, inflammatory, infectious, and neurodegenerative disorders.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"513-531"},"PeriodicalIF":5.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 OPA1 pathway in Autosomal Dominant Optic Atrophy (ADOA): 25 years from gene discovery to therapeutic strategy. 针对常染色体显性视神经萎缩（ADOA）的OPA1通路：从基因发现到治疗策略的25年。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-05-01 Epub Date: 2026-05-12 DOI: 10.1080/14728222.2026.2671678

Marcel V Alavi

{"title":"Targeting the OPA1 pathway in Autosomal Dominant Optic Atrophy (ADOA): 25 years from gene discovery to therapeutic strategy.","authors":"Marcel V Alavi","doi":"10.1080/14728222.2026.2671678","DOIUrl":"10.1080/14728222.2026.2671678","url":null,"abstract":"Introduction: Autosomal Dominant Optic Atrophy (ADOA) is a rare hereditary optic neuropathy primarily caused by OPA1 mutations. Retinal ganglion cell (RGC) loss results in variable visual impairments, occasionally accompanied by extra-ocular manifestations. ADOA also involves a developmental component consistent with OPA1's essential role in mitochondrial fusion, cristae organization, and quality control. As such, ADOA serves as a paradigm for studying mitochondrial contributions to neurodegeneration.Areas covered: This article provides a comprehensive overview of ADOA, covering genetic and clinical aspects while distinguishing between degenerative and developmental features of the pathology. The author examines OPA1 function and assesses emerging therapeutic strategies-ranging from gene augmentation and small-molecule therapeutics to alternative targets-before appraising translational challenges.Expert opinion: Antisense therapies targeting OPA1 haploinsufficiency are among the more advanced ADOA treatments currently under human safety evaluation, with other modalities following closely in development. However, the field still lacks robust clinical endpoints for the highly variable and slowly progressive phenotype. Furthermore, developmental RGC loss may limit therapeutic efficacy of late-stage interventions-a challenge compounded by the difficulty of early diagnosis. Nevertheless, the FDA's recent shift toward Bayesian statistical frameworks and the emergence of neuroprotective alternative targets are expected to streamline the clinical development for ADOA.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"451-461"},"PeriodicalIF":5.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Identifying targets at the blood-brain barrier for treating vascular cognitive impairment and dementia. 确定治疗血管性认知障碍和痴呆的血脑屏障靶点。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-05-01 Epub Date: 2026-05-12 DOI: 10.1080/14728222.2026.2671696

Adnan Akif, Thi Thanh My Nguyen, Benjamin L Hao, Jianxiong Jiang, Xiang Li, Yibo Fan, Jiukuan Hao

{"title":"Identifying targets at the blood-brain barrier for treating vascular cognitive impairment and dementia.","authors":"Adnan Akif, Thi Thanh My Nguyen, Benjamin L Hao, Jianxiong Jiang, Xiang Li, Yibo Fan, Jiukuan Hao","doi":"10.1080/14728222.2026.2671696","DOIUrl":"10.1080/14728222.2026.2671696","url":null,"abstract":"Introduction: Vascular cognitive impairment and dementia (VCID) arise from chronic cerebrovascular dysfunction that compromises the blood-brain barrier (BBB), a critical interface maintaining neural homeostasis. The BBB's neurovascular unit (NVU) integrates endothelial cells, pericytes, astrocytes, and neurons, whose coordinated function preserves cerebral integrity. Persistent hypoperfusion, oxidative stress, and inflammation disrupt this system, triggering tight-junction degradation, impaired nutrient transport, and neuroinflammatory cascades that accelerate white matter damage and cognitive decline.Areas covered: This review examines recent advances linking BBB dysfunction to VCID pathogenesis and summarizes pharmacological, cellular, and technological strategies to restore barrier function. Small molecules targeting oxidative and inflammatory signaling, cell-based therapies (mesenchymal and endothelial progenitors, iPSC-derived lineages), and advanced delivery platforms such as focused ultrasound and nanocarriers are evaluated for their potential to protect or repair the BBB.Expert opinion: Effective VCID management will require precision medicine approaches integrating BBB biomarkers, vascular risk control, and targeted anti-inflammatory or regenerative therapies. Ongoing innovation in imaging, molecular diagnostics, and delivery systems offers a realistic path toward early intervention and prevention of cognitive decline by safeguarding neurovascular integrity.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"499-511"},"PeriodicalIF":5.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Relevance of lipid droplets in metabolic dysfunction-associated steatotic liver disease. 脂滴与代谢功能障碍相关的脂肪变性肝病的相关性

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-05-01 Epub Date: 2026-05-11 DOI: 10.1080/14728222.2026.2671694

Ralf Weiskirchen, Amedeo Lonardo

{"title":"Relevance of lipid droplets in metabolic dysfunction-associated steatotic liver disease.","authors":"Ralf Weiskirchen, Amedeo Lonardo","doi":"10.1080/14728222.2026.2671694","DOIUrl":"10.1080/14728222.2026.2671694","url":null,"abstract":"Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally, leading to cirrhosis, hepatocellular carcinoma, and increased liver-related mortality, along with extrahepatic risks. A hallmark of MASLD is excessive neutral lipid accumulation in hepatocytes as cytosolic lipid droplets (LDs), which are now recognized as dynamic organelles involved in lipid storage, energy metabolism, signaling, and stress responses. Understanding LD pathobiology in MASLD is vital for insights into disease mechanisms and targeted therapies.Areas covered: This review outlines current knowledge on LD biogenesis, growth, and turnover in hepatocytes and their disruption in MASLD. We discuss LDs' dual role as protective buffers against lipotoxicity and contributors to disease progression when lipid fluxes are altered. The involvement of LDs in non-parenchymal cells like hepatic stellate cells and macrophages in inflammation and fibrogenesis is examined. Human genetic studies linking LD-associated proteins (e.g. PNPLA3) to MASLD susceptibility are also discussed.Expert opinion: LDs are crucial in MASLD pathogenesis, integrating genetic factors with metabolic signals. Future therapies should focus on normalizing lipid flux and LD functions rather than indiscriminately depleting them to avoid disrupting protective storage mechanisms.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"473-497"},"PeriodicalIF":5.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Promise of ANGPTL3 as a therapeutic target for controlling cholesterol levels. ANGPTL3有望成为控制胆固醇水平的治疗靶点。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-05-01 Epub Date: 2026-05-12 DOI: 10.1080/14728222.2026.2671686

Robert A Hegele

{"title":"Promise of ANGPTL3 as a therapeutic target for controlling cholesterol levels.","authors":"Robert A Hegele","doi":"10.1080/14728222.2026.2671686","DOIUrl":"10.1080/14728222.2026.2671686","url":null,"abstract":"Introduction: Angiopoietin-like protein 3 (ANGPTL3) has emerged over the past decade as one of the most intriguing therapeutic targets in lipid metabolism.Areas covered: Genetic deficiency of ANGPTL3 in humans produces a striking pan-hypolipidemic phenotype, with reductions in triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), accompanied by protection from atherosclerotic cardiovascular disease (ASCVD). These observations rapidly catalyzed the development of pharmacologic strategies to inhibit ANGPTL3 using monoclonal antibodies (e.g. evinacumab), antisense oligonucleotides (e.g. vupanorsen), small interfering ribonucleic acid (e.g. zodasiran and solbinsiran), and most recently genome-editing approaches (e.g. VERVE-201 and CTX310). However, clinical experience has revealed a more complex and context-dependent biology than initially anticipated.Expert opinion: This review examines whether ANGPTL3 should be considered a clinically meaningful cholesterol-lowering target, as exemplified by efficacy of ANGPTL3 inhibition in homozygous familial hypercholesterolemia, or whether its principal therapeutic value lies in modulation of triglyceride-rich lipoproteins and remnant cholesterol, with secondary effects on LDL-C. The degree of hypertriglyceridemia in the patient's baseline lipid profile appears to be an important determinant of drug response. Drawing on genetic, mechanistic, and clinical trial data, the promise and limitations of ANGPTL3 inhibition are considered and its potential place in future lipid-lowering strategies is outlined.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"463-471"},"PeriodicalIF":5.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 insights into the PRLR-Hippo-YAP axis in breast cancer therapeutics. PRLR-hippo-YAP轴在乳腺癌治疗中的分子洞察。

IF 4.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-05-01 Epub Date: 2026-05-13 DOI: 10.1080/14728222.2026.2671687

Suhad Ali, Jean-Jacques Lebrun

引用次数: 0

Advances in CGRP therapeutic targets for migraine: where do we stand 5 years later? 偏头痛CGRP治疗靶点的进展：5年后我们在哪里？

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-05-01 Epub Date: 2026-05-14 DOI: 10.1080/14728222.2026.2671693

Adriana Della Pietra, Andrew F Russo

{"title":"Advances in CGRP therapeutic targets for migraine: where do we stand 5 years later?","authors":"Adriana Della Pietra, Andrew F Russo","doi":"10.1080/14728222.2026.2671693","DOIUrl":"10.1080/14728222.2026.2671693","url":null,"abstract":"Introduction: The past 5 years of success with calcitonin gene-related peptide (CGRP) based drugs has transformed migraine into a relatively treatable neurological disorder. There are now eight monoclonal antibodies and small-molecule receptor antagonists available for the acute and preventive treatment of migraine. However, while the drugs have been remarkably effective and safe so far, they do not work for everyone, and some adverse effects have become apparent.Areas covered: We describe key developments with the CGRP therapeutics regarding real-world effectiveness and safety. Emerging evidence supporting combinatorial treatment strategies within the CGRP drugs and with onabotulinumtoxinA will be discussed.Expert opinion: The future of peptides is bright for migraine therapeutics. A monoclonal antibody against pituitary adenylate cyclase-activating polypeptide (PACAP) has shown promise in two clinical trials and evidence suggests that CGRP and PACAP therapeutics may be complementary. A second CGRP receptor, AMY1, which is also activated by another peptide, amylin, is a new therapeutic target validated by clinical and preclinical data. Building on the CGRP story, centrally acting CGRP antagonists are an untapped area that should be explored. We close with a brief speculation on possible future applications of CGRP drugs for other disorders.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"437-450"},"PeriodicalIF":5.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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