Expert Opinion on Therapeutic Targets最新文献

Exploiting ER proteostasis in malaria: protein disulphide isomerases as selective antimalarial targets. 利用内质网蛋白酶在疟疾：蛋白二硫异构酶作为选择性抗疟疾靶点。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-09-06 DOI: 10.1080/14728222.2026.2723486

Adeshina I Odugbemi, Wendy Mthembu, Tawanda Zininga

{"title":"Exploiting ER proteostasis in malaria: protein disulphide isomerases as selective antimalarial targets.","authors":"Adeshina I Odugbemi, Wendy Mthembu, Tawanda Zininga","doi":"10.1080/14728222.2026.2723486","DOIUrl":"10.1080/14728222.2026.2723486","url":null,"abstract":"Introduction: The emergence of partial resistance to artemisinin-based therapies has intensified the search for antimalarial targets beyond classical kinases and proteases. Protein disulfide isomerases (PDIs) have emerged as attractive candidates due to their roles in endoplasmic reticulum (ER) oxidative folding, redox homeostasis, and survival under proteotoxic stress. Several Plasmodium falciparum PDI family members are essential during asexual blood stages and contribute to parasite transmission.Areas covered: We summarize PfPDI architecture, catalytic and holdase functions, and their integration within the parasite ER folding network, highlighting structural divergence from human PDIs that may enable selective inhibition. We review PDI-directed chemotypes, including covalent active-site binders and non-covalent/allosteric modulators, and highlight the absence of PfPDI-selective probes with validated intracellular mechanisms. We further discuss approaches for target validation, including chemoproteomics, activity-based profiling, and chemical genetics, alongside medicinal chemistry considerations for achieving exposure to an intracellular ER target. Finally, we examine PfPDIs within a proteostasis-stress framework and discuss combination strategies with protein-damaging agents such as artemisinin derivatives.Expert opinion: Progress will depend on structure-guided targeting of divergent non-catalytic surfaces, optimization of intracellular and ER exposure, and rigorous in-parasite target-engagement studies. PfPDI inhibitors are most likely to succeed as components of resistance-robust combination therapies.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-21"},"PeriodicalIF":5.1,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849887","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 NLRP3 inflammasome pathway associated with neuroinflammation mediated Alzheimer's disease: pre-clinical and clinical status of emerging therapeutics. 靶向与神经炎症介导的阿尔茨海默病相关的NLRP3炎性体途径：新兴治疗方法的临床前和临床状况

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-08-27 DOI: 10.1080/14728222.2026.2723488

Devesh Yaduvanshi, Rishabh Aggarwal, Sameeya A, Mohd Aqil, Mohd Mujeeb, Mohd Akhtar, Abul Kalam Najmi

{"title":"Targeting the NLRP3 inflammasome pathway associated with neuroinflammation mediated Alzheimer's disease: pre-clinical and clinical status of emerging therapeutics.","authors":"Devesh Yaduvanshi, Rishabh Aggarwal, Sameeya A, Mohd Aqil, Mohd Mujeeb, Mohd Akhtar, Abul Kalam Najmi","doi":"10.1080/14728222.2026.2723488","DOIUrl":"10.1080/14728222.2026.2723488","url":null,"abstract":"Introducion: Alzheimer's disease (AD) is a rising global health problem, but current treatments only target symptoms rather than fixing their underlying root causes. A major pathological feature is neuroinflammation, which is specifically driven by the Nucleotide-binding domain, Leucine-rich-repeat and Pyrin domain-containing 3 (NLRP3) inflammasome cascade, which acts as a 'molecular switch' that causes immune cells in the brain to trigger robust secretion of pro-inflammatory cytokines (e.g. IL-1β, IL-18) and pyroptosis, causing systemic inflammation, consequently, neuroinflammation.Areas covered: This review breaks down the pathways triggered by immune cells activation (neurotoxic microglial phenotype) and mainly focuses on the NLRP3 inflammasome neuroinflammation pathway. It explores the promising therapeutic potential of specific bioactive phytochemicals, repurposed and novel synthetic drugs/agents, to shut-down this molecular switch, i.e. NLRP3 inflammasome pathway.Expert opinion: To truly stop AD, we must shift our focus from treating merely the symptoms, by stopping the disease at its roots. While discovering the novel NLRP3 inflammasome inhibitors is exciting, the biggest hurdle is getting them into the brain. The future of AD treatment relies on combining these targeted drugs with advanced nanotechnology, like nano-particles, to successfully cross the blood-brain barrier (BBB) and safely deliver the drugs exactly where they are needed.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-20"},"PeriodicalIF":5.1,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812492","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

Hepatic T-cell dysfunction in chronic liver disease and hepatocellular carcinoma: a spatial systems-immunology framework for precision immunotherapy. 慢性肝病和肝细胞癌的肝t细胞功能障碍：精确免疫治疗的空间系统免疫学框架。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-08-26 DOI: 10.1080/14728222.2026.2708824

Wanvisa Udomsinprasert

{"title":"Hepatic T-cell dysfunction in chronic liver disease and hepatocellular carcinoma: a spatial systems-immunology framework for precision immunotherapy.","authors":"Wanvisa Udomsinprasert","doi":"10.1080/14728222.2026.2708824","DOIUrl":"10.1080/14728222.2026.2708824","url":null,"abstract":"Background: Chronic liver diseases, including chronic viral hepatitis, metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and hepatocellular carcinoma (HCC), are characterized by progressive immune dysregulation driving chronic inflammation, fibrosis, and hepatocarcinogenesis. Despite hepatic T-cell dysfunction being a defining characteristic of these conditions, it is primarily examined through discrete molecular pathways instead of as an integrated component of the hepatic immune system. This reductionist perspective has limited mechanistic understanding and the development of durable immunotherapeutic strategies.Areas covered: This review proposes a spatial systems-immunology framework as its central conceptual contribution. The framework explains hepatic T-cell dysfunction as an emergent systems-level state arising from coordinated interactions among immune, metabolic, stromal, vascular, and spatial regulatory programs. The translational implications of this framework for biomarker-guided precision immunotherapy in chronic liver disease and HCC are further discussed.Expert opinion: Future advances in liver immunotherapy should prioritize mechanism-based combination therapies guided by multidimensional immune, metabolic, stromal, and spatial biomarkers rather than the ongoing optimisation of individual molecular targets. In this review, it is argued that the proposed spatial systems-immunology framework provides a practical foundation for this transition and may improve patient stratification, therapeutic durability, and long-term clinical outcomes in chronic liver disease and HCC.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-19"},"PeriodicalIF":5.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618972","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 targeting of CDK9 in oncology therapeutics: avenues for translational impact. CDK9在肿瘤治疗中的分子靶向：转化影响的途径。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-08-25 DOI: 10.1080/14728222.2026.2723483

Tiyao Liu, Zhongran Liu, Wenjing Wei, Shudong Wang, Shaoqiang Wang, Yuanyuan Zhang, Ziyi Gao, Wenhao Wu

{"title":"Molecular targeting of CDK9 in oncology therapeutics: avenues for translational impact.","authors":"Tiyao Liu, Zhongran Liu, Wenjing Wei, Shudong Wang, Shaoqiang Wang, Yuanyuan Zhang, Ziyi Gao, Wenhao Wu","doi":"10.1080/14728222.2026.2723483","DOIUrl":"10.1080/14728222.2026.2723483","url":null,"abstract":"Background: Cyclin-dependent kinase 9 (CDK9) is a central regulator of RNA polymerase II elongation and has emerged as a therapeutic target in tumors characterized by transcriptional addiction. Growing interest in selective inhibitors and targeted degraders has renewed attention to the translational potential of CDK9-directed therapy.Areas covered: This review summarizes the molecular functions of the CDK9/positive transcription elongation factor b (P-TEFb) axis, its role in super-enhancer-driven oncogenic programs, and the mechanisms by which CDK9 inhibition promotes apoptosis, epigenetic derepression, and tumor microenvironment remodeling. We also discuss representative small-molecule inhibitors and proteolysis-targeting chimera (PROTAC) degraders, emerging biomarkers for patient stratification, rational combination strategies, and the current landscape of resistance mechanisms.Expert opinion: Selective targeting of CDK9 offers a promising route for treating refractory malignancies, particularly when guided by transcriptional dependency, biomarker-informed dosing, and rational combination design. Future progress will likely depend on improving therapeutic index, refining translational biomarkers, and anticipating adaptive resistance during clinical development.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-12"},"PeriodicalIF":5.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790038","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 targets in proliferative vitreoretinopathy: rethinking prevention, treatment and drug delivery after rhegmatogenous retinal detachment. 增殖性玻璃体视网膜病变的分子靶点：对孔源性视网膜脱离后的预防、治疗和给药的重新思考。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-08-25 DOI: 10.1080/14728222.2026.2724125

Enrico Bernardi, William Mitchell, Carla Troyas, Rodrigo Anguita

{"title":"Molecular targets in proliferative vitreoretinopathy: rethinking prevention, treatment and drug delivery after rhegmatogenous retinal detachment.","authors":"Enrico Bernardi, William Mitchell, Carla Troyas, Rodrigo Anguita","doi":"10.1080/14728222.2026.2724125","DOIUrl":"https://doi.org/10.1080/14728222.2026.2724125","url":null,"abstract":"Introduction: Proliferative vitreoretinopathy (PVR) is the leading cause of surgical failure after rhegmatogenous retinal detachment repair and the principal indication for repeat vitreoretinal surgery, yet four decades of mechanistic research have not produced an effective pharmacological adjunct. This review reexamines why, and asks how prevention, treatment and drug delivery might be reframed.Areas covered: This narrative expert review conceptualizes PVR as a temporally evolving, overlapping fibro-inflammatory continuum spanning inflammation and chemotaxis, retinal pigment epithelial activation and epithelial-mesenchymal transition, proliferation, extracellular matrix deposition, membrane contraction and neurodegeneration. Informed by the current literature and the authors' experience, we appraise the key cellular drivers, the agents tested or proposed (corticosteroids, antimetabolites, anti-VEGF, anti-fibrotics and RNA-based approaches), emerging biology (mechanobiology, senescence, exosomes, epigenetics and ferroptosis), and the pharmacokinetic barriers and delivery platforms that constrain translation in the vitrectomized and oil-filled eye.Expert opinion: Repeated trial failure reflects not a single failed target but recurring problems of patient selection, disease timing, pharmacokinetic mismatch, biological redundancy and trial design. Progress will require biomarker-enriched prevention in high-risk eyes, stage-matched combination therapy, delivery systems suited to the vitrectomized eye, and adequately powered multicenter trials pairing high-quality surgery with appropriately timed pharmacology.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818004","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

Assessing the preclinical progress in the therapeutic targeting of axial spondyloarthritis. 评估轴型脊柱炎治疗靶向性的临床前进展。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-08-22 DOI: 10.1080/14728222.2026.2722195

Ronan Soudy, Manon Jacoutot, Paul Gervaise, Chiara Bonini, Aida Boukamel, Luiza M Araujo, Félicie Costantino, Simon Glatigny, Maxime Breban

{"title":"Assessing the preclinical progress in the therapeutic targeting of axial spondyloarthritis.","authors":"Ronan Soudy, Manon Jacoutot, Paul Gervaise, Chiara Bonini, Aida Boukamel, Luiza M Araujo, Félicie Costantino, Simon Glatigny, Maxime Breban","doi":"10.1080/14728222.2026.2722195","DOIUrl":"https://doi.org/10.1080/14728222.2026.2722195","url":null,"abstract":"Introduction: Axial spondyloarthritis (SpA) is a chronic inflammatory rheumatism affecting predominantly the axial skeleton and frequently also the peripheral joints, often associated with specific extra-musculoskeletal manifestations. This complex disease is still poorly understood resulting in a lack of cure. While symptomatic treatments are available, preclinical models/analyses are needed to identify new therapeutic targets in order to improve axial SpA treatment.Areas covered: We discussed strengths and weaknesses of preclinical models used to identify and validate emerging therapeutic targets.Expert opinion: Progress in developing new therapies for axial SpA remains slow due to its biological complexity and limited understanding of early disease mechanisms. Current treatments mainly target downstream inflammation, contributing to persistent unmet needs and variable responses. Future progress will rely on more pathophysiologically relevant models, interdisciplinary approaches, and integration of insights from related diseases to accelerate personalized therapeutic development.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-11"},"PeriodicalIF":5.1,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790127","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

Interleukin-6 as a therapeutic target in diabetic macular edema: current evidence and future perspectives. 白细胞介素-6作为糖尿病黄斑水肿的治疗靶点：目前的证据和未来的观点。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-08-18 DOI: 10.1080/14728222.2026.2720412

Hidetaka Noma, Tatsuya Mimura

{"title":"Interleukin-6 as a therapeutic target in diabetic macular edema: current evidence and future perspectives.","authors":"Hidetaka Noma, Tatsuya Mimura","doi":"10.1080/14728222.2026.2720412","DOIUrl":"10.1080/14728222.2026.2720412","url":null,"abstract":"Introduction: Diabetic macular edema (DME) is a major cause of vision loss in diabetic retinopathy. Although anti-vascular endothelial growth factor (VEGF) therapy is the current standard treatment, many patients show incomplete responses, indicating the contribution of VEGF-independent mechanisms. Increasing evidence identifies interleukin-6 (IL-6) as a key mediator of inflammation, blood-retinal barrier disruption, and retinal vascular dysfunction in DME.Areas covered: This review summarizes the biological functions and signaling pathways of IL-6 in DME and examines the clinical relevance of elevated intraocular IL-6 levels. We discuss the crosstalk between IL-6 and VEGF, review current evidence for IL-6-targeting agents, including tocilizumab and sarilumab, and evaluate their therapeutic potential, particularly in treatment-resistant DME.Expert opinion: IL-6 acts as a central hub cytokine linking chronic inflammation, vascular permeability, and retinal microvascular injury. By modulating both VEGF-dependent and VEGF-independent pathways, IL-6 inhibition represents a promising therapeutic strategy for refractory DME. Although direct clinical evidence remains limited, advances in biomarker-guided patient selection, local drug delivery systems, and combination approaches with anti-VEGF therapy may facilitate the development of precision medicine for DME.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-14"},"PeriodicalIF":5.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759188","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

BCAA metabolic reprogramming identifies BCKDK as a therapeutic target in cancer. BCAA代谢重编程确定BCKDK作为癌症的治疗靶点。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-30 DOI: 10.1080/14728222.2026.2709804

Zhihan Li, Yuxuan Zhou, Li Zhang, Quanjun Yang

{"title":"BCAA metabolic reprogramming identifies BCKDK as a therapeutic target in cancer.","authors":"Zhihan Li, Yuxuan Zhou, Li Zhang, Quanjun Yang","doi":"10.1080/14728222.2026.2709804","DOIUrl":"10.1080/14728222.2026.2709804","url":null,"abstract":"Introduction: Branched-chain keto acid dehydrogenase kinase (BCKDK) is a mitochondrial kinase that suppresses branched-chain amino acid (BCAA) oxidative catabolism by phosphorylating and inhibiting the branched-chain α-keto acid dehydrogenase complex. Beyond this canonical metabolic function, accumulating evidence indicates that aberrant BCKDK activation contributes to tumor metabolic rewiring, signaling adaptation, malignant progression and therapy resistance.Areas covered: This review summarizes the regulatory position of BCKDK in BCAA catabolism, its context-dependent functions across tumor types, and recent progress in BCKDK inhibitor development. Although selected non-oncological studies are discussed to inform inhibitor mechanism, pharmacology and safety, this review focuses on the oncology relevance of BCKDK. Particular attention is given to the transition from early proof-of-concept inhibitors to BT2-derived allosteric compounds, Pfizer-developed clinical candidates, and emerging non-BT2 scaffolds or alternative binding regions. A PubMed search was conducted to identify relevant studies on BCKDK, BCAA metabolism, cancer progression and BCKDK-targeted inhibitors.Expert opinion: BCKDK is unlikely to function as a universal pan-cancer target. Its therapeutic value will depend on identifying tumor contexts with true BCKDK dependency, especially those relying on BCKDK-driven metabolic adaptation or downstream signaling. For BCKDK inhibitors, future development should integrate biochemical potency with mechanism-aligned conformational effects, long-term pharmacological consequences and biomarker-supported patient stratification.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-15"},"PeriodicalIF":5.1,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577608","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 therapy-induced senescence-associated secretory phenotype and epithelial-mesenchymal transition axis in ovarian cancer: molecular mechanisms and therapeutic opportunities. 卵巢癌治疗诱导的衰老相关分泌表型和上皮-间质转化轴：分子机制和治疗机会。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-30 DOI: 10.1080/14728222.2026.2709798

Ruiqi Wang, Dongsheng Shang, Zhigang Tu, Hanqing Liu

{"title":"The therapy-induced senescence-associated secretory phenotype and epithelial-mesenchymal transition axis in ovarian cancer: molecular mechanisms and therapeutic opportunities.","authors":"Ruiqi Wang, Dongsheng Shang, Zhigang Tu, Hanqing Liu","doi":"10.1080/14728222.2026.2709798","DOIUrl":"https://doi.org/10.1080/14728222.2026.2709798","url":null,"abstract":"Introduction: Therapy-induced senescence (TIS) is an important response to anticancer treatments in ovarian cancer, which can trigger the senescence-associated secretory phenotype (SASP) that may contribute to epithelial-mesenchymal transition (EMT), tumor migration, invasion, and adhesion. This review delineates the molecular mechanisms through linking TIS-mediated SASP to EMT and evaluates emerging therapeutic opportunities.Areas covered: We discuss key regulatory pathways including cGAS-STING, NF-κB, p53, and STAT3 that orchestrate SASP components such as IL-6, IL-8, and TGF-β to activate EMT transcription factors. Bioinformatics analyses of clinical datasets identify SASP factors (IL-6, AREG, c-JUN, TIMP1, THBS1) as critical EMT mediators, with hub genes including COL4A2, COL5A2, PDGFRB, and FBN1 involved in ECM remodeling and cell adhesion. SASP promotes ovarian cancer cell adhesion through MMP-mediated ECM degradation, release of matrix-bound growth factors, generation of adhesive fragments, and induction of mesothelial-mesenchymal transition. We evaluate emerging therapeutic strategies targeting this axis, including senolytics to eliminate senescent cells, senomorphics to suppress SASP secretion, and targeted inhibition of specific SASP components.Expert opinion: Although preclinical advances are promising, challenges in model systems and real-time SASP monitoring remain; future integrated multi-omics analyses and personalized therapeutic approaches are needed to translate these findings into improved ovarian cancer outcomes.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-18"},"PeriodicalIF":5.1,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619025","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

Breakthroughs in our molecular understanding of therapeutic targets for pulmonary hypertension. 我们对肺动脉高压治疗靶点的分子认识取得突破。

IF 5.1 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2026-07-29 DOI: 10.1080/14728222.2026.2709796

Gerrit Bredeck, Alejandro Cruz-Utrilla, Eduardo Oliver

{"title":"Breakthroughs in our molecular understanding of therapeutic targets for pulmonary hypertension.","authors":"Gerrit Bredeck, Alejandro Cruz-Utrilla, Eduardo Oliver","doi":"10.1080/14728222.2026.2709796","DOIUrl":"10.1080/14728222.2026.2709796","url":null,"abstract":"Introduction: Pulmonary hypertension (PH) is characterized by progressive pulmonary vascular remodeling, rising right-ventricular afterload, and eventual maladaptation, which is a major determinant of prognosis. While established therapies mainly target vasoconstrictive pathways, recent development has shifted toward disease-modifying strategies that address remodeling, inflammation, and metabolic dysfunction in PH patients.Areas covered: This Special Report summarizes selected breakthrough therapeutic targets in PH, focusing on mechanisms supported by strong causal rationale and evaluated in at least Phase II clinical testing. Covered pathways include bone morphogenetic proteins/activin signaling rebalancing, growth factor and kinase inhibition, zinc transport targeting, inflammatory and immune-directed approaches, and metabolic modulation. We emphasize translational relevance, current clinical status, and key challenges limiting broader implementation of these approaches.Expert opinion: The next advance in PH treatment will depend not only on identifying effective targets but also on improving precision in their deployment. Three barriers are especially important: responder heterogeneity, incomplete benefit-risk stratification, and uncertainty about target engagement in vivo. Therefore, biomarker-guided enrichment, integrated safety profiling, and practical pharmacodynamic readouts should become central elements of trial design. In parallel, expansion of the therapeutic toolbox, including stress-sensing, adrenergic, senescence, and hypoxia-related pathways, may increase the likelihood of matching individual patients to effective disease-modifying therapy.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-10"},"PeriodicalIF":5.1,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561182","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