Expert Opinion on Therapeutic Targets最新文献

Targeted therapeutic strategies for the kidney. 肾脏靶向治疗策略。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-11-03 DOI: 10.1080/14728222.2024.2421756

Fei Yuan, Lilach O Lerman

引用次数: 0

Advantages and disadvantages of targeting senescent endothelial cells in cardiovascular and cerebrovascular diseases based on small extracellular vesicles. 利用细胞外小泡靶向治疗心脑血管疾病中的衰老内皮细胞的利弊。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-30 DOI: 10.1080/14728222.2024.2421760

Wen Ma, Tingyuan Zhou, Songling Tang, Lu Gan, Yu Cao

{"title":"Advantages and disadvantages of targeting senescent endothelial cells in cardiovascular and cerebrovascular diseases based on small extracellular vesicles.","authors":"Wen Ma, Tingyuan Zhou, Songling Tang, Lu Gan, Yu Cao","doi":"10.1080/14728222.2024.2421760","DOIUrl":"https://doi.org/10.1080/14728222.2024.2421760","url":null,"abstract":"Introduction: With the growth of the aging population, age-related diseases have become a heavy global burden, particularly cardiovascular and cerebrovascular diseases (CVDs). Endothelial cell (EC) senescence constitutes an essential factor in the development of CVDs, prompting increased focus on strategies to alleviate or reverse EC senescence.Areas covered: Small extracellular vesicles (sEVs) are cell-derived membrane structures, that contain proteins, lipids, RNAs, metabolites, growth factors and cytokines. They are widely used in treating CVDs, and show remarkable therapeutic potential in alleviating age-related CVDs by inhibiting or reversing EC senescence. However, unclear anti-senescence mechanism poses challenges for clinical application of sEVs, and a systematic review is lacking.Expert opinion: Targeting senescent ECs with sEVs in age-related CVDs treatment represents a promising therapeutic strategy, with modifying sEVs and their contents emerging as a prevalent approach. Nevertheless, challenges remain, such as identifying and selectively targeting senescent cells, understanding the consequences of removing senescent ECs and senescence-associated secretory phenotype (SASP), and assessing the side effects of therapeutic sEVs on CVDs. More substantial experimental and clinical data are needed to advance clinical practice.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544542","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

What is holding back preclinical GPR119 agonists from their potential as the therapeutics of type 2 diabetes? 是什么阻碍了临床前 GPR119 激动剂发挥治疗 2 型糖尿病的潜力？

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-29 DOI: 10.1080/14728222.2024.2421751

Jing Hu, Yu Cao, Lianxiang Duan, Jinghua Peng

引用次数: 0

Potential molecular targets for the pharmacologic management of non-traumatic osteonecrosis. 非创伤性骨坏死药物治疗的潜在分子靶点。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-29 DOI: 10.1080/14728222.2024.2421755

Edward Y Cheng, Alireza Mirzaei

{"title":"Potential molecular targets for the pharmacologic management of non-traumatic osteonecrosis.","authors":"Edward Y Cheng, Alireza Mirzaei","doi":"10.1080/14728222.2024.2421755","DOIUrl":"10.1080/14728222.2024.2421755","url":null,"abstract":"Introduction: Non-traumatic osteonecrosis is a debilitating condition marked by bone death, primarily due to reduced blood supply. Currently, no effective pharmacologic intervention is available to manage this condition effectively.Areas covered: Lipid metabolic disorders, chronic inflammation, vascular dysfunction, coagulopathy, and impaired bone homeostasis are suggested as the key pathogenic mechanisms involved in the development of non-traumatic osteonecrosis. Targeting any of these dysfunctions offers a potential avenue for pharmacologic intervention. However, the potential molecular targets for pharmacologic treatment of non-traumatic osteonecrosis remain underexplored. In this study, we reviewed available databases to compile a comprehensive set of pathogenic mechanisms and corresponding therapeutic targets for non-traumatic osteonecrosis.Expert opinion: Evidence suggests that a single pathogenic mechanism cannot fully explain the development of osteonecrosis, supporting the adoption of a multi-pathogenic theory. This theory implies that effective management of non-traumatic osteonecrosis requires targeting multiple pathogenic mechanisms simultaneously. Moreover, the same pathogenic mechanisms are unlikely to explain osteonecrosis development in patients with different etiologies. Consequently, a one-size-fits-all approach to medication is unlikely to be effective across all types of non-traumatic osteonecrosis. Future research should, therefore, focus on developing multi-target pharmacologic treatments tailored to the specific etiology of non-traumatic osteonecrosis.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521481","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 TRPV1 pain pathway in osteoarthritis of the knee. 针对膝骨关节炎的 TRPV1 疼痛通路。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-25 DOI: 10.1080/14728222.2024.2416961

Ali Mobasheri, François Rannou, Stefan Ivanavicius, Philip G Conaghan

{"title":"Targeting the TRPV1 pain pathway in osteoarthritis of the knee.","authors":"Ali Mobasheri, François Rannou, Stefan Ivanavicius, Philip G Conaghan","doi":"10.1080/14728222.2024.2416961","DOIUrl":"https://doi.org/10.1080/14728222.2024.2416961","url":null,"abstract":"Introduction: The growing prevalence and lack of effective pain therapies for knee osteoarthritis (KOA) results in a substantial unmet need for novel analgesic therapies. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed in subsets of nociceptive sensory neurons and has major roles in pain transmission and regulation. In the structures of the knee joint, nociceptors are present in abundance.Areas covered: TRPV1-expressing nociceptors in the knee represent a rational target to modulate activity at the origin of the pain pathway in KOA and may avoid systemic side effects seen with currently available analgesics. TRPV1 antagonists can induce analgesia, but hyperthermia and thermal hypesthesia side effects have limited their utility. Clinical development of TRPV1 agonists for pain management has progressed further than that of TRPV1 antagonists. Capsaicin and resiniferatoxin have provided proof-of-concept for the modulation of TRPV1 activity in KOA.Expert opinion: Intra-articular administration of TRPV1 agonists enables direct delivery to target nerve terminals in the knee, offering a potentially transformative approach for the management of pain associated with KOA. Here, we explore the advances in understanding innervation of the knee joint in KOA, the role of TRPV1-expressing neurons and progress in developing TRPV1 modulators for KOA.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497723","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

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-21 DOI: 10.1080/14728222.2024.2415014

Glykeria N Daneva, Panagiotis Tsiakanikas, Panagiotis G Adamopoulos, Andreas Scorilas

引用次数: 0

Expression of Concern: Overexpression of HMGA2 in breast cancer promotes cell proliferation, migration, invasion and stemness. 关注表达：乳腺癌中 HMGA2 的过表达会促进细胞增殖、迁移、侵袭和干性。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-21 DOI: 10.1080/14728222.2024.2417515

引用次数: 0

Progress and challenges in glypican-3 targeting for hepatocellular carcinoma therapy. 以 glypican-3 为靶点治疗肝细胞癌的进展与挑战。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-20 DOI: 10.1080/14728222.2024.2416975

Arnaud Couzinet, Toshihiro Suzuki, Tetsuya Nakatsura

{"title":"Progress and challenges in glypican-3 targeting for hepatocellular carcinoma therapy.","authors":"Arnaud Couzinet, Toshihiro Suzuki, Tetsuya Nakatsura","doi":"10.1080/14728222.2024.2416975","DOIUrl":"https://doi.org/10.1080/14728222.2024.2416975","url":null,"abstract":"Introduction: Glypican-3 (GPC3) is a cell membrane-anchored heparan sulfate proteoglycan that has recently garnered attention as a cancer antigen owing to its high expression in numerous cancers, particularly hepatocellular carcinoma (HCC), and to limited expression in adult normal tissue.Areas covered: Here, we propose the potential of GPC3 as a cancer antigen based on our experience with the GPC3 peptide vaccine against HCC, having developed a vaccine that progressed from preclinical studies to first-in-human clinical trials. In this review, we present a summary of the current status and future prospects of immunotherapies targeting GPC3 by focusing on clinical trials; peptide vaccines, mRNA vaccines, antibody therapy, and chimeric antigen receptor/T-cell receptor - T-cell therapy and discuss additional strategies for effectively eliminating HCC through immunotherapy.Expert opinion: GPC3 is an ideal cancer antigen for HCC immunotherapy. In resectable HCC, immunotherapies that leverage physiological immune surveillance, immune checkpoint inhibitors, and GPC3-target cancer vaccines appear promising in preventing recurrence and could be considered as a prophylactic adjuvant therapy. However, in advanced HCC, clinical trials have not demonstrated sufficient anti-tumor efficacy, in contrast with preclinical studies. Reverse translation, bedside-to-bench research, is crucial to identify the factors that have hindered GPC3 target immunotherapies.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461382","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

Exploring PKG signaling as a therapeutic avenue for pressure overload, ischemia, and HFpEF. 探索 PKG 信号转导作为压力过载、缺血和高房血症的治疗途径。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-09-27 DOI: 10.1080/14728222.2024.2400093

S Zhazykbayeva, H Budde, M Kaçmaz, Y Zemedie, H Osman, R Hassoun, K Jaquet, I Akin, I El-Battrawy, M Herwig, N Hamdani

{"title":"Exploring PKG signaling as a therapeutic avenue for pressure overload, ischemia, and HFpEF.","authors":"S Zhazykbayeva, H Budde, M Kaçmaz, Y Zemedie, H Osman, R Hassoun, K Jaquet, I Akin, I El-Battrawy, M Herwig, N Hamdani","doi":"10.1080/14728222.2024.2400093","DOIUrl":"https://doi.org/10.1080/14728222.2024.2400093","url":null,"abstract":"Introduction: Heart failure (HF) is a complex and heterogeneous syndrome resulting from any diastolic or systolic dysfunction of the cardiac muscle. In addition to comorbid conditions, pressure overload, and myocardial ischemia are associated with cardiac remodeling which manifests as extracellular matrix (ECM) perturbations, impaired cellular responses, and subsequent ventricular dysfunction.Areas covered: The current review discusses the main aspects of the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway (cGMP-PKG) pathway modulators and highlights the promising outcomes of its novel pharmacological boosters.Expert opinion: Among several signaling pathways involved in the pathogenesis of pressure overload, ischemia and HF with preserved ejection fraction (HFpEF) is cGMP-PKG pathway. This pathway plays a pivotal role in the regulation of cardiac contractility, and modulation of cGMP-PKG signaling, contributing to the development of the diseases. Ventricular cardiomyocytes of HF patients and animal models are known to exhibit reduced cGMP levels and disturbed cGMP signaling including hypophosphorylation of PKG downstream targets. However, restoration of cGMP-PKG signaling improves cardiomyocyte function and promotes cardioprotective effects.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344281","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

Target potential of miRNAs in ulcerative colitis: what do we know? 溃疡性结肠炎中 MicroRNA 的靶标潜力：我们知道些什么？

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-09-25 DOI: 10.1080/14728222.2024.2408423

Peeyush Kumar, Saurabh Kedia, Vineet Ahuja

{"title":"Target potential of miRNAs in ulcerative colitis: what do we know?","authors":"Peeyush Kumar, Saurabh Kedia, Vineet Ahuja","doi":"10.1080/14728222.2024.2408423","DOIUrl":"10.1080/14728222.2024.2408423","url":null,"abstract":"Introduction: The global rise in ulcerative colitis (UC) incidence highlights the urgent need for enhanced diagnostic and therapeutic strategies. Recent advances in genome-wide association studies (GWAS) have identified genetic loci associated with UC, providing insights into the disease's molecular mechanisms, including immune modulation, mucosal defense, and epithelial barrier function. Despite these findings, many GWAS signals are located in non-coding regions and are linked to low risk, suggesting that protein-coding genes alone do not fully explain UC's pathophysiology. Emerging research emphasizes the potential of microRNAs (miRNAs) as biomarkers and therapeutic targets due to their crucial role in UC. This review explores the current understanding of miRNAs in UC, including their mechanisms of action and their potential as both biomarkers and therapeutic targets. The present review provides the latest update on their potential as a biomarker and therapeutic target.Areas covered: This review synthesizes an extensive literature search on miRNAs in UC, focusing on their roles in the mucosal barrier, innate and adaptive immunity, and their potential applications as biomarkers and therapeutic modalities.Expert opinion: While miRNAs present promising opportunities as biomarkers and novel therapeutic agents in UC, challenges in validation, specificity, delivery, and clinical application need to be addressed through rigorous, large-scale studies.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282691","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