{"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":"<p><strong>Introduction: </strong>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.</p><p><strong>Areas covered: </strong>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.</p><p><strong>Expert opinion: </strong>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.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"829-841"},"PeriodicalIF":5.4,"publicationDate":"2024-10-01","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}
{"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":"10.1080/14728222.2024.2416975","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Areas covered: </strong>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.</p><p><strong>Expert opinion: </strong>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.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"895-909"},"PeriodicalIF":5.4,"publicationDate":"2024-10-01","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}
{"title":"What is holding back preclinical GPR119 agonists from their potential as the therapeutics of type 2 diabetes?","authors":"Jing Hu, Yu Cao, Lianxiang Duan, Jinghua Peng","doi":"10.1080/14728222.2024.2421751","DOIUrl":"10.1080/14728222.2024.2421751","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"825-828"},"PeriodicalIF":5.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521482","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}
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":"10.1080/14728222.2024.2416961","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Areas covered: </strong>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.</p><p><strong>Expert opinion: </strong>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.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"843-856"},"PeriodicalIF":5.4,"publicationDate":"2024-10-01","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}
{"title":"Expression of Concern: Overexpression of HMGA2 in breast cancer promotes cell proliferation, migration, invasion and stemness.","authors":"","doi":"10.1080/14728222.2024.2417515","DOIUrl":"10.1080/14728222.2024.2417515","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"923"},"PeriodicalIF":5.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461380","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}
{"title":"The role of Nrf2 in immune cells and inflammatory autoimmune diseases: a comprehensive review.","authors":"Wang-Dong Xu,Chan Yang,An-Fang Huang","doi":"10.1080/14728222.2024.2401518","DOIUrl":"https://doi.org/10.1080/14728222.2024.2401518","url":null,"abstract":"INTRODUCTIONNrf2 regulates mild stress, chronic inflammation, and metabolic changes by regulating different immune cells via downstream signaling. Collection of information about the role of Nrf2 in inflammatory autoimmune diseases will better understand the therapeutic potential of targeting Nrf2 in these diseases.AREAS COVEREDIn this review, we comprehensively discussed biological function of Nrf2 in different immune cells, including Nrf2 preventing oxidative tissue injury, affecting apoptosis of immune cells and inflammatory cytokine production. Moreover, we discussed the role of Nrf2 in the development of inflammatory autoimmune diseases.EXPERT OPINIONNrf2 binds to downstream signaling molecules and then provides durable protection against different cellular and organ stress. It has emerged as an important target for inflammatory autoimmune diseases. Development of Nrf2 modulator drugs needs to consider factors such as target specificity, short/long term safety, disease indication identification, and the extent of variation in Nrf2 activity. We carefully discussed the dual role of Nrf2 in some diseases, which helps to better target Nrf2 in the future.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"12 1","pages":"1-18"},"PeriodicalIF":5.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178925","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}
{"title":"Can we target insulin signalling for cognition therapeutics?","authors":"Simone Macrì, Giovanni Laviola","doi":"10.1080/14728222.2024.2407821","DOIUrl":"https://doi.org/10.1080/14728222.2024.2407821","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"28 9","pages":"713-717"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344282","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}
{"title":"Combined cancer immunotherapy based on targeting adenosine pathway and PD-1/PDL-1 axis.","authors":"Mehrdad Fathi, Asieh Zarei, Ata Moghimi, Pooya Jalali, Zahra Salehi, Sharareh Gholamin, Farhad Jadidi-Niaragh","doi":"10.1080/14728222.2024.2405090","DOIUrl":"10.1080/14728222.2024.2405090","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer immunotherapy has revolutionized the field of oncology, offering new hope to patients with advanced malignancies. Tumor-induced immunosuppression limits the effectiveness of current immunotherapeutic strategies, such as PD-1/PDL-1 checkpoint inhibitors. Adenosine, a purine nucleoside molecule, is crucial to this immunosuppression because it stops T cells from activating and helps regulatory T cells grow. Targeting the adenosine pathway and blocking PD-1/PDL-1 is a potential way to boost the immune system's response to tumors.</p><p><strong>Areas covered: </strong>This review discusses the current understanding of the adenosine pathway in tumor immunology and the preclinical and clinical data supporting the combination of adenosine pathway inhibitors with PD-1/PDL-1 blockade. We also discuss the challenges and future directions for developing combination immunotherapy targeting the adenosine pathway and the PD-1/PDL-1 axis for cancer treatment.</p><p><strong>Expert opinion: </strong>The fact that the adenosine signaling pathway controls many immune system processes suggests that it has a wide range of therapeutic uses. Within the next five years, there will be tremendous progress in this area, and the standard of care for treating malignant tumors will have switched from point-to-point therapy to the integration of immunological networks comprised of multiple signaling pathways, like the adenosine axis.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"757-777"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282689","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}
Jonathan van Eyll, Robert Prior, Sylvain Celanire, Ludo Van Den Bosch, Frederik Rombouts
{"title":"Therapeutic indications for HDAC6 inhibitors in the peripheral and central nervous disorders.","authors":"Jonathan van Eyll, Robert Prior, Sylvain Celanire, Ludo Van Den Bosch, Frederik Rombouts","doi":"10.1080/14728222.2024.2404571","DOIUrl":"10.1080/14728222.2024.2404571","url":null,"abstract":"<p><strong>Introduction: </strong>Inhibition of the enzymatic function of HDAC6 is currently being explored in clinical trials ranging from peripheral neuropathies to cancers. Advances in selective HDAC6 inhibitor discovery allowed studying highly efficacious brain penetrant and peripheral restrictive compounds for treating PNS and CNS indications.</p><p><strong>Areas covered: </strong>This review explores the multifactorial role of HDAC6 in cells, the common pathological hallmarks of PNS and CNS disorders, and how HDAC6 modulates these mechanisms. Pharmacological inhibition of HDAC6 and genetic knockout/knockdown studies as a therapeutic strategy in PNS and CNS indications were analyzed. Furthermore, we describe the recent developments in HDAC6 PET tracers and their utility in CNS indications. Finally, we explore the advancements and challenges with HDAC6 inhibitor compounds, such as hydroxamic acid, fluoromethyl oxadiazoles, HDAC6 degraders, and thiol-based inhibitors.</p><p><strong>Expert opinion: </strong>Based on extensive preclinical evidence, pharmacological inhibition of HDAC6 is a promising approach for treating both PNS and CNS disorders, given its involvement in neurodegeneration and aging-related cellular processes. Despite the progress in the development of selective HDAC6 inhibitors, safety concerns remain regarding their chronic administration in PNS and CNS indications, and the development of novel compound classes and modalities inhibiting HDAC6 function offer a way to mitigate some of these safety concerns.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"719-737"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282692","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}
{"title":"Innovations in treating acute graft-versus-host disease: a review of preclinical targets and strategies.","authors":"Haoliang Duan, Yuhua Ru, Jia Chen","doi":"10.1080/14728222.2024.2405091","DOIUrl":"10.1080/14728222.2024.2405091","url":null,"abstract":"<p><strong>Introduction: </strong>Acute graft-versus-host disease (aGVHD) is a major complication of post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) that severely impacts patient survival and quality of life. Despite advancements in standard care, therapeutic outcomes remain suboptimal, necessitating the exploration of innovative strategies.</p><p><strong>Areas covered: </strong>This review synthesizes preclinical research focusing on novel therapeutic targets and strategies that may enhance treatment efficacy. We critically analyzed the role of specific T-cell subsets, cytokine modulators, and intracellular signaling pathways in reducing aGVHD severity. Emphasis is placed on experimental findings that illuminate the mechanisms of immune tolerance and survival improvement. We discuss the translation of these findings into potential clinical trials and evaluate the challenges and progress in implementing these strategies, including scalability and impact on the graft-versus-leukemia (GVL) effect.</p><p><strong>Expert opinion: </strong>Our review summarizes the latest therapeutic targets and strategies in preclinical research for aGVHD, aiming to bridge the gap between clinical and experimental medicine. By integrating immunology, genetics, and cytology, we seek to enhance the translation of preclinical findings into clinical strategies. This multidisciplinary approach is expected to improve patient outcomes in aGVHD treatment, ultimately leading to more effective and safer therapies.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"807-824"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282690","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}