Expert Opinion on Therapeutic Targets最新文献_第5页

The protective role of SIRT1 in cardiovascular disease: from molecular mechanisms to potential therapeutic strategies. SIRT1在心血管疾病中的保护作用：从分子机制到潜在的治疗策略

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-01 Epub Date: 2026-06-21 DOI: 10.1080/14728222.2026.2690139

Haixin Ma, Shuya Wang, Zijian Dang, Wentao Xie, Ning Li, Jiayan Li, Yang Yang, Zhenxiao Jin

{"title":"The protective role of SIRT1 in cardiovascular disease: from molecular mechanisms to potential therapeutic strategies.","authors":"Haixin Ma, Shuya Wang, Zijian Dang, Wentao Xie, Ning Li, Jiayan Li, Yang Yang, Zhenxiao Jin","doi":"10.1080/14728222.2026.2690139","DOIUrl":"10.1080/14728222.2026.2690139","url":null,"abstract":"Introduction: Cardiovascular diseases (CVDs) pose a significant threat to the health of middle-aged and elderly people. They are widely recognized as a major public health concern. The sirtuin (SIRT) family comprises seven proteins (SIRT1-SIRT7), all of which contain a highly conserved nicotinamide adenine dinucleotide (NAD+)-binding catalytic domain. Notably, SIRT1 influences the development and progression of CVDs by regulating biological processes such as inflammation, immune responses, oxidative stress, and autophagy.Areas covered: This review summarizes the biological functions of SIRT1 and its role in major cardiovascular conditions, with particular attention to cell-type-specific effects. It examines the preclinical efficacy of SIRT1 activators, such as resveratrol and SRT1720, and discusses challenges including dose dependency, specificity, and barriers to clinical translation. A comprehensive literature search (PubMed, Web of Science, Scopus; 2000-April 2026) was conducted to identify studies on SIRT1 in CVDs, with a focus on mechanistic insights and therapeutic relevance.Expert opinion: We believe that developing highly specific SIRT1 activators, identifying predictive biomarkers, and elucidating tissue-selective regulatory mechanisms can amplify SIRT1's protective effects in cardiac diseases. Current and future clinical trials should establish the safety and efficacy of SIRT1-targeted therapies at the earliest possible stage.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"757-784"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249919","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

The evolving bioinformatic approaches to identifying genetic targets of promise in cancers. 不断发展的生物信息学方法来识别癌症中有希望的基因靶标。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-01 Epub Date: 2026-07-22 DOI: 10.1080/14728222.2026.2706463

Vijay Kumar, Darin Mansor Mathkor, Shafiul Haque

{"title":"The evolving bioinformatic approaches to identifying genetic targets of promise in cancers.","authors":"Vijay Kumar, Darin Mansor Mathkor, Shafiul Haque","doi":"10.1080/14728222.2026.2706463","DOIUrl":"10.1080/14728222.2026.2706463","url":null,"abstract":"Introduction: The search for actionable genetic targets in cancer has evolved substantially over the past decade. Earlier approaches were focused on single genes or individual molecular alterations, but this is insufficient to capture tumor complexity in vivo. Cancer is influenced not only by genomic changes but also by transcriptional plasticity, epigenetic regulation, protein activity, metabolic adaptation, and dynamic interactions with the tumor microenvironment. Consequently, bioinformatic target discovery has shifted toward integrative, systems-level models of tumor biology.Areas covered: This article discusses the evolution of bioinformatic approaches for cancer target identification, underscoring key achievements and persistent challenges. Advances from 2018-2025 are analyzed, including multi-omics integration, single-cell sequencing, and functional genomics, which enhance the identification of context-dependent molecular vulnerabilities. Also, the role of machine learning in analyzing large-scale datasets to uncover potential therapeutic targets is discussed.Expert opinion: Precision medicine now recognizes that genetic background alone is insufficient to define actionable targets. Factors such as cell type, tumor spatial context, environmental influences, clonal lineage and epigenetic state are vital. Current bioinformatic frameworks increasingly incorporate artificial intelligence, offer unprecedented opportunities to integrate these dimensions and refine target discovery.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"647-658"},"PeriodicalIF":5.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469800","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

Therapeutic targeting of DNA repair pathway dysregulation in aging, cancer, and neurodegeneration. DNA修复通路失调在衰老、癌症和神经退行性疾病中的靶向治疗。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-06-01 Epub Date: 2026-06-07 DOI: 10.1080/14728222.2026.2683686

Vipin Kumar, Mohmmad Kashif, Vivek Singh, Rahul Singh Rawat, Aamir Khan, Gautam Chandra Sarkar, Misba Majood

{"title":"Therapeutic targeting of DNA repair pathway dysregulation in aging, cancer, and neurodegeneration.","authors":"Vipin Kumar, Mohmmad Kashif, Vivek Singh, Rahul Singh Rawat, Aamir Khan, Gautam Chandra Sarkar, Misba Majood","doi":"10.1080/14728222.2026.2683686","DOIUrl":"10.1080/14728222.2026.2683686","url":null,"abstract":"Introduction: Genome maintenance is increasingly recognized as a shared vulnerability across aging, cancer, and neurodegeneration, yet the therapeutic implications of pathway-specific dysregulation of DNA repair remain incompletely defined.Areas covered: This review integrates recent mechanistic and translational literature on how base excision repair, nucleotide excision repair, mismatch repair, homologous recombination, canonical non-homologous end joining, and alternative end joining are remodeled across these conditions. We discuss how oxidative stress, replication stress, telomere dysfunction, mitochondrial injury, and persistent DNA damage response signaling drive senescence and inflammation; how tumor cells exploit repair rewiring to survive genotoxic stress and acquire resistance; and how post-mitotic neurons are limited by restricted repair redundancy. We also summarize biomarkers for repair-state stratification and emerging strategies targeting PARP, ATR, ATM, DNA-PK, POLQ, and cGAS-STING.Expert opinion: Clinical translation will depend less on single-gene alterations than on defining context-specific repair states and pathway dependencies. Such stratification should enable rational combinations that either restore repair fidelity in aging and neurodegeneration or exploit repair addiction in cancer.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"611-634"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143332","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

Insights into the therapeutic targeting of ASIC3 in pain: hurdles for clinical development. ASIC3在疼痛中的靶向治疗：临床发展的障碍

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-06-01 Epub Date: 2026-06-07 DOI: 10.1080/14728222.2026.2682785

Chih-Hung Chi, Cheng-Han Lee, Chih-Cheng Chen

{"title":"Insights into the therapeutic targeting of ASIC3 in pain: hurdles for clinical development.","authors":"Chih-Hung Chi, Cheng-Han Lee, Chih-Cheng Chen","doi":"10.1080/14728222.2026.2682785","DOIUrl":"10.1080/14728222.2026.2682785","url":null,"abstract":"Introduction: Acid-sensing ion channel 3 (ASIC3) is a promising therapeutic target for pain because of its unique peripheral expression profile in somatosensory neurons and channel properties for sensing mild extracellular acidosis associated with inflammation, ischemia, and metabolic changes.Areas covered: As a highly sensitive acid sensor, ASIC3's activity is also enhanced by endogenous modulators in the inflammatory 'soup,' such as arachidonic acid and hypertonicity, and by cold temperatures. Furthermore, ASIC3 activation can be independent of acid changes by molecules such as lysophosphatidylcholine 16:0, a lipid identified as a critical trigger in chronic joint pain and stress-induced widespread pain. Beyond nociception, ASIC3 is strongly implicated in multimodal sensory perception in non-nociceptive neurons. In particular, ASIC3 is expressed in proprioceptors and acts as a mechanical sensor for proprioception via a tether model of mechanotransduction, although direct evidence of tethering elements remains missing. Intriguingly, proprioceptor ASIC3 also plays an important role in acid sensation, called sngception to distinguish the acid-like discomfort (sng, pronounced / səŋ /) from pain sensation.Expert opinion: Therapeutic strategies targeting ASIC3 must account for its intricate molecular crosstalk and unexpected dual role in nociception and sngception as well as its role in maintaining chronic pain and sng.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"555-569"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053733","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

RNA-centric approaches in amyotrophic lateral sclerosis: prospects for future therapeutics. 以rna为中心的方法治疗肌萎缩性侧索硬化症：未来治疗的前景。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-06-01 Epub Date: 2026-06-08 DOI: 10.1080/14728222.2026.2682782

Valentina La Cognata, Giulia Gentile, Giovanna Morello, Maria Guarnaccia, Sebastiano Cavallaro

{"title":"RNA-centric approaches in amyotrophic lateral sclerosis: prospects for future therapeutics.","authors":"Valentina La Cognata, Giulia Gentile, Giovanna Morello, Maria Guarnaccia, Sebastiano Cavallaro","doi":"10.1080/14728222.2026.2682782","DOIUrl":"10.1080/14728222.2026.2682782","url":null,"abstract":"Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by profound clinical and molecular heterogeneity, which has substantially hindered the development of effective therapies. Significant advances in ALS research have been driven by the study of RNA biology, together with the implementation of advanced transcriptomic technologies and artificial intelligence-based algorithms, which are assuming a transformative role in reshaping the field.Areas covered: We discuss how genome-wide expression profiling enables the identification of molecular signatures for drug discovery and repurposing, facilitates the stratification of patients into biologically distinct subtypes for more refined clinical trials, and guides the development of novel nucleic acid-based therapies. Furthermore, we explore the potential of transcriptomics to identify molecular vulnerabilities during pre-symptomatic stages, paving the way for early intervention.Expert opinion: The convergence of transcriptomics and artificial intelligence is poised to fundamentally redefine ALS, transforming it from a single clinical entity into a spectrum of molecularly defined disorders, each potentially amenable to targeted therapeutic intervention. While challenges in translating high-dimensional data into clinical practice remain, the integration of transcriptomics with advanced computational tools promises to accelerate the transition toward a new era of personalized medicine in ALS.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"571-583"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053777","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

The AT₂ receptor as a potential target for autosomal dominant polycystic kidney disease therapy? AT2受体作为常染色体显性多囊肾病治疗的潜在靶点？

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-06-01 Epub Date: 2026-06-15 DOI: 10.1080/14728222.2026.2682784

Yan Wang, Sharon Ricardo, Robert Widdop

引用次数: 0

Investigating metabotropic glutamate receptors as molecular targets for next-generation pharmacotherapies for alcohol use disorder. 研究代谢性谷氨酸受体作为下一代药物治疗酒精使用障碍的分子靶点。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-06-01 Epub Date: 2026-05-17 DOI: 10.1080/14728222.2026.2675555

Dominic Obraitis, Jason Barry, Dawei Li

{"title":"Investigating metabotropic glutamate receptors as molecular targets for next-generation pharmacotherapies for alcohol use disorder.","authors":"Dominic Obraitis, Jason Barry, Dawei Li","doi":"10.1080/14728222.2026.2675555","DOIUrl":"10.1080/14728222.2026.2675555","url":null,"abstract":"Introduction: Alcohol use disorder (AUD) is a major public health concern with few available pharmacotherapy options. There remains a critical need to identify novel molecular targets for more effective treatments. Evidence suggests that AUD is associated with dysregulated glutamatergic neurotransmission, including a hyperglutamatergic state that contributes to the development and maintenance of alcohol seeking behaviors.Areas covered: Recent advances in characterizing neuronal, glial, and synaptic changes underlying AUD pathophysiology have identified the metabotropic glutamate receptor 2 (mGluR2) as a promising therapeutic target. As a presynaptic glutamate autoreceptor, pharmacological activation of mGluR2 may help modulate altered glutamatergic signaling observed in AUD. This review summarizes preclinical evidence demonstrating that mGluR2 agonists and positive allosteric modulators can effectively reduce alcohol seeking behaviors. This review also discusses emerging evidence linking glutamatergic dysregulation with neuroinflammatory processes in AUD.Expert opinion: Consistent findings across multiple preclinical studies support continued investigation of mGluR2-targeted therapies as potential interventions for AUD treatment. Restoring glutamatergic homeostasis through mGluR2 modulation may help reduce alcohol seeking behaviors and ultimately improve clinical outcomes in patients with AUD. Future research should also examine the genetic and genomic processes linking neuroinflammation and glutamatergic dysfunction as another avenue for developing novel therapeutic interventions for AUD management.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"547-553"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The biological role of CCR4 and its ligands CCL17 and CCL22 in atopic dermatitis: therapeutic implications and future directions. CCR4及其配体CCL17和CCL22在特应性皮炎中的生物学作用：治疗意义和未来方向

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-06-01 Epub Date: 2026-06-26 DOI: 10.1080/14728222.2026.2690137

Dante Dahabreh, Dev Patel, Ester Del Duca, Ross Corriden, Dirk G Brockstedt, Emma Guttman-Yassky

{"title":"The biological role of CCR4 and its ligands CCL17 and CCL22 in atopic dermatitis: therapeutic implications and future directions.","authors":"Dante Dahabreh, Dev Patel, Ester Del Duca, Ross Corriden, Dirk G Brockstedt, Emma Guttman-Yassky","doi":"10.1080/14728222.2026.2690137","DOIUrl":"10.1080/14728222.2026.2690137","url":null,"abstract":"Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disorder driven by Th2-related cytokines, including interleukin-4 (IL-4) and IL-13. Recent single-cell sequencing and proteomic studies have demonstrated that sustained immune activity can persist even after treatment with the anti-IL-4 receptor alpha antibody dupilumab. Thus, targeting C-C chemokine receptor 4 (CCR4), which is highly expressed by Th2 cells and drives their migration into the inflamed tissues such as skin in response CCL17 (TARC) and CCL22 (MDC), could be a promising therapeutic approach for the treatment of AD.Areas covered: This review summarizes: 1) the role of CCR4 and its primary endogenous ligands CCL17 and CCL22 in AD pathobiology; 2) the molecular pharmacology and associated signaling pathways of CCR4; and 3) the current landscape of CCR4 inhibitors, including key challenges in their discovery/development. The implications of CCR4 pharmacology in the development of new therapeutic agents are also discussed.Expert opinion: New insights into the function and molecular pharmacology of CCR4 have informed the discovery of molecules that target CCR4 directly (e.g. small-molecule allosteric inhibitors) as well as ones that target the CCL17/CCL22/CCR4 signaling axis broadly (e.g. neutraligands). Ongoing efforts to develop therapies targeting this pathway may yield new treatments for AD.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"585-597"},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327787","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 inflammatory persistence in axial spondyloarthritis: from cytokine blockade to pathway convergence. 针对轴型脊柱炎的炎症持续性：从细胞因子阻断到途径收敛。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-06-01 Epub Date: 2026-06-14 DOI: 10.1080/14728222.2026.2689392

Dimitrios Deligeorgakis, Nikolaos Kougkas

引用次数: 0

Hepatocyte nuclear factor 4α - prospects for therapeutic targeting. 肝细胞核因子4α -靶向治疗的前景。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-06-01 Epub Date: 2026-07-01 DOI: 10.1080/14728222.2026.2690135

Yusuke Inoue

引用次数: 0