{"title":"Promising therapeutic targets for the treatment of urine storage dysfunction: what’s the status?","authors":"Karl-Erik Andersson","doi":"10.1080/14728222.2024.2344698","DOIUrl":"https://doi.org/10.1080/14728222.2024.2344698","url":null,"abstract":"Opinions differ on what drugs have both a rationale and a development potential for the treatment of bladder storage dysfunction.In the present review, the focus is given to small molecule blockers...","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"57 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140610671","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}
Carlos Arrabal-Gómez, Pedro Serrano-Castro, Jose Andrés Sánchez-Pérez, Natalia Garcia-Casares, Kjell Fuxe, Dasiel Borroto-Escuela, Manuel Narváez
{"title":"Potentiation of antidepressant effects: NPY1R agonist and ketamine synergy enhances TrkB signaling and neurogenesis in the ventral hippocampus","authors":"Carlos Arrabal-Gómez, Pedro Serrano-Castro, Jose Andrés Sánchez-Pérez, Natalia Garcia-Casares, Kjell Fuxe, Dasiel Borroto-Escuela, Manuel Narváez","doi":"10.1080/14728222.2024.2342524","DOIUrl":"https://doi.org/10.1080/14728222.2024.2342524","url":null,"abstract":"Major Depressive Disorder (MDD) poses a significant challenge to global health, with current treatments often limited by efficacy and onset delays. This study explores the synergistic antidepressan...","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"56 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599131","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}
Dasiel Borroto-Escuela, Pedro Serrano-Castro, Jose Andrés Sánchez-Pérez, Miguel Angel Barbancho-Fernández, Kjell Fuxe, Manuel Narváez
{"title":"Enhanced neuronal survival and BDNF elevation via long-term co-activation of galanin 2 (GALR2) and neuropeptide Y1 receptors (NPY1R): potential therapeutic targets for Major depressive disorder","authors":"Dasiel Borroto-Escuela, Pedro Serrano-Castro, Jose Andrés Sánchez-Pérez, Miguel Angel Barbancho-Fernández, Kjell Fuxe, Manuel Narváez","doi":"10.1080/14728222.2024.2342517","DOIUrl":"https://doi.org/10.1080/14728222.2024.2342517","url":null,"abstract":"Major Depressive Disorder (MDD) is a prevalent and debilitating condition, necessitating novel therapeutic strategies due to the limited efficacy and adverse effects of current treatments. We explo...","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"96 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598729","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}
Prasanna Anjaneyulu Yakkalaa, Shaik Rahaman, P.S. Lakshmi Soukya, Sajeli Ahil Begum, A Kamal
{"title":"An update on the development on tubulin inhibitors for the treatment of solid tumors","authors":"Prasanna Anjaneyulu Yakkalaa, Shaik Rahaman, P.S. Lakshmi Soukya, Sajeli Ahil Begum, A Kamal","doi":"10.1080/14728222.2024.2341630","DOIUrl":"https://doi.org/10.1080/14728222.2024.2341630","url":null,"abstract":"Microtubules play a vital role in cancer therapeutics. They are implicated in tumorigenesis, thus inhibiting tubulin polymerization in cancer cells, and have now become a significant target for ant...","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"116 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599220","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":"Guillain-Barré syndrome: immunopathogenesis and therapeutic targets.","authors":"Shan Liu, Wei Wei Zhang, Linpei Jia, Hong-Liang Zhang","doi":"10.1080/14728222.2024.2330435","DOIUrl":"10.1080/14728222.2024.2330435","url":null,"abstract":"<p><strong>Introduction: </strong>Guillain-Barré syndrome (GBS) is a group of acute immune-mediated disorders in the peripheral nervous system. Both infectious and noninfectious factors are associated with GBS, which may act as triggers of autoimmune responses leading to neural damage and dysfunction.</p><p><strong>Areas covered: </strong>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccines as well as flaviviruses have been associated with GBS, although a robust conclusion has yet to be reached. Immunomodulatory treatments, including intravenous immunoglobulins (IVIg) and plasma exchange (PE), have long been the first-line therapies for GBS. Depending on GBS subtype and severity at initial presentation, the efficacy of IVIg and PE can be variable. Several new therapies showing benefits to experimental animals merit further investigation before translation into clinical practice. We review the state-of-the-art knowledge on the immunopathogenesis of GBS in the context of coronavirus disease 2019 (COVID-19). Immunomodulatory therapies in GBS, including IVIg, PE, corticosteroids, and potential therapies, are summarized.</p><p><strong>Expert opinion: </strong>The association with SARS-CoV-2 remains uncertain, with geographical differences that are difficult to explain. Evidence and guidelines are lacking for the decision-making of initiating immunomodulatory therapies in mildly affected patients or patients with regional subtypes of GBS.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"131-143"},"PeriodicalIF":5.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101380","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}
Oliver D Tavabie, Siamak Salehi, Varuna R Aluvihare
{"title":"The challenges and potential of microRNA-based therapy for patients with liver failure syndromes and hepatocellular carcinoma.","authors":"Oliver D Tavabie, Siamak Salehi, Varuna R Aluvihare","doi":"10.1080/14728222.2024.2331598","DOIUrl":"10.1080/14728222.2024.2331598","url":null,"abstract":"<p><strong>Introduction: </strong>Morbidity and mortality from liver disease continues to rise worldwide. There are currently limited curative treatments for patients with liver failure syndromes, encompassing acute liver failure and decompensated cirrhosis states, outside of transplantation. Whilst there have been improvements in therapeutic options for patients with hepatocellular carcinoma (HCC), there remain challenges necessitating novel therapeutic agents. microRNA have long been seen as potential therapeutic targets but there has been limited clinical translation.</p><p><strong>Areas covered: </strong>We will discuss the limitations of conventional non-transplant management of patients with liver failure syndromes and HCC. We will provide an overview of microRNA and the challenges in developing and delivering microRNA-based therapeutic agents. We will finally provide an overview of microRNA-based therapeutic agents which have progressed to clinical trials.</p><p><strong>Expert opinion: </strong>microRNA have great potential to be developed into therapeutic agents due to their association with critical biological processes which govern health and disease. Utilizing microRNA sponges to target multiple microRNA associated with specific biological processes may improve their therapeutic efficacy. However, there needs to be significant improvements in delivery systems to ensure the safe delivery of microRNA to target sites and minimize systemic distribution. This currently significantly impacts the clinical translation of microRNA-based therapeutic agents.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"179-191"},"PeriodicalIF":5.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131115","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 potential for OGG1 inhibition to be a therapeutic strategy for pulmonary diseases.","authors":"Lang Pan, Istvan Boldogh","doi":"10.1080/14728222.2024.2317900","DOIUrl":"10.1080/14728222.2024.2317900","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary diseases impose a daunting burden on healthcare systems and societies. Current treatment approaches primarily address symptoms, underscoring the urgency for the development of innovative pharmaceutical solutions. A noteworthy focus lies in targeting enzymes recognizing oxidatively modified DNA bases within gene regulatory elements, given their pivotal role in governing gene expression.</p><p><strong>Areas covered: </strong>This review delves into the intricate interplay between the substrate-specific binding of 8-oxoguanine DNA glycosylase 1 (OGG1) and epigenetic regulation, with a focal point on elucidating the molecular underpinnings and their biological implications. The absence of OGG1 distinctly attenuates the binding of transcription factors to cis elements, thereby modulating pro-inflammatory or pro-fibrotic transcriptional activity. Through a synergy of experimental insights gained from cell culture studies and murine models, utilizing prototype OGG1 inhibitors (O8, TH5487, and SU0268), a promising panorama emerges. These investigations underscore the absence of cytotoxicity and the establishment of a favorable tolerance profile for these OGG1 inhibitors.</p><p><strong>Expert opinion: </strong>Thus, the strategic targeting of the active site pocket of OGG1 through the application of small molecules introduces an innovative trajectory for advancing redox medicine. This approach holds particular significance in the context of pulmonary diseases, offering a refined avenue for their management.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"117-130"},"PeriodicalIF":5.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722209","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}
Prasanna Anjaneyulu Yakkala, Fatima Naaz, Syed Shafi, Ahmed Kamal
{"title":"PI3K and tankyrase inhibitors as therapeutic targets in colorectal cancer.","authors":"Prasanna Anjaneyulu Yakkala, Fatima Naaz, Syed Shafi, Ahmed Kamal","doi":"10.1080/14728222.2024.2331015","DOIUrl":"10.1080/14728222.2024.2331015","url":null,"abstract":"<p><strong>Introduction: </strong>The pathways like Wingless-related integration (Wnt/β-catenin) and PI3K play an important role in colorectal cancer (CRC) development; however, their roles are distinct in the process of oncogenesis. Despite their differences, these pathways interact through feedback mechanisms and regulate the common effectors both in the upstream and the downstream processes in normal and pathological conditions. Their ability to reciprocally control each other is a primary resistance mechanism for the selective inhibitors in CRC.</p><p><strong>Area covered: </strong>This review highlights the Wnt/β-catenin and PI3K pathways that are interrelated in CRC, recent advances and some key perspectives in developing inhibitors that could target the tankyrase enzyme and PI3K, apart from a brief description of the potential of dual inhibitors of PI3K and Tankyrases (TNKS).</p><p><strong>Expert opinion: </strong>Recent research has focused on overcoming the challenges particularly relating to the resistance and efficacy of dual inhibitors targeting PI3K and tankyrase proteins. Despite these challenges, PI3K as well as tankyrases remain promising therapeutic targets for the treatment of solid tumors. The design of potent inhibitors is crucial to effectively block these protein signaling pathways. Moreover, it is essential to explore the potential of dual-target inhibition of other signaling pathways in conjunction with PI3K and tankyrase.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"159-177"},"PeriodicalIF":5.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143056","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}
Annarosa Arcangeli, Jessica Iorio, Claudia Duranti
{"title":"Targeting the hERG1 and β1 integrin complex for cancer treatment.","authors":"Annarosa Arcangeli, Jessica Iorio, Claudia Duranti","doi":"10.1080/14728222.2024.2318449","DOIUrl":"10.1080/14728222.2024.2318449","url":null,"abstract":"<p><strong>Introduction: </strong>Despite great advances, novel therapeutic targets and strategies are still needed, in particular for some carcinomas in the metastatic stage (breast cancer, colorectal cancer, pancreatic ductal adenocarcinoma and the clear cell renal carcinoma). Ion channels may be considered good cancer biomarkers and targets for antineoplastic therapy. These concepts are particularly relevant considering the hERG1 potassium channel as a novel target for antineoplastic therapy.</p><p><strong>Areas covered: </strong>A great deal of evidence demonstrates that hERG1 is aberrantly expressed in human cancers, in particular in aggressive carcinomas. A relevant cornerstone was the discovery that, in cancer cells, the channel is present in a very peculiar conformation, strictly bound to the β1 subunit of integrin receptors. The hERG1/β1 integrin complex does not occur in the heart. Starting from this evidence, we developed a novel single chain bispecific antibody (scDb-hERG1-β1), which specifically targets the hERG1/β1 integrin complex and exerts antineoplastic effects in preclinical experiments.</p><p><strong>Expert opinion: </strong>Since hERG1 blockade cannot be pursued for antineoplastic therapy due to the severe cardiac toxic effects (ventricular arrhythmias) that many hERG1 blockers exert, different strategies must be identified to specifically target hERG1 in cancer. The targeting of the hERG1/β1 integrin complex through the bispecific antibody scDb-hERG1-β1 can overcome such hindrances.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"145-157"},"PeriodicalIF":5.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899627","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":"Considerations on the implementation of MAP4K4 inhibitors as cancer treatment.","authors":"Jaime Gonzalez-Montero, Mauricio Burotto","doi":"10.1080/14728222.2024.2326211","DOIUrl":"10.1080/14728222.2024.2326211","url":null,"abstract":"","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"113-115"},"PeriodicalIF":5.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989702","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}