Masoud Sotoudeh, Vahid Mansouri, Ramin Shakeri, Bahareh Sharififard, Nasim Sajadi, Vahid Haghpanah, Mahmood Naderi
{"title":"Decoding the expression pattern of MUC3A in gastric adenocarcinoma: unveiling the key to successful immunotherapy","authors":"Masoud Sotoudeh, Vahid Mansouri, Ramin Shakeri, Bahareh Sharififard, Nasim Sajadi, Vahid Haghpanah, Mahmood Naderi","doi":"10.1080/14728222.2023.2293764","DOIUrl":"https://doi.org/10.1080/14728222.2023.2293764","url":null,"abstract":"Despite the promise of immunotherapy for gastric adenocarcinoma, resistance is common, necessitating the validation of new targets. Based on our previous bioinformatics analysis, the MUC3A antigen ...","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138562313","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}
Basharat Ahmad Bhat, Ifra Saifi, Nizar A Khamjan, Syed Suhail Hamdani, Abdullah Algaissi, Safeena Rashid, Mohammed M Alshehri, Showkat Ahmad Ganie, Mohtashim Lohani, Siddig Ibrahim Abdelwahab, Sajad Ahmad Dar
{"title":"Exploring the tumor immune microenvironment in ovarian cancer: a way-out to the therapeutic roadmap.","authors":"Basharat Ahmad Bhat, Ifra Saifi, Nizar A Khamjan, Syed Suhail Hamdani, Abdullah Algaissi, Safeena Rashid, Mohammed M Alshehri, Showkat Ahmad Ganie, Mohtashim Lohani, Siddig Ibrahim Abdelwahab, Sajad Ahmad Dar","doi":"10.1080/14728222.2023.2259096","DOIUrl":"10.1080/14728222.2023.2259096","url":null,"abstract":"<p><strong>Introduction: </strong>Despite cancer treatment strides, mortality due to ovarian cancer remains high globally. While immunotherapy has proven effective in treating cancers with low cure rates, it has limitations. Growing evidence suggests that both tumoral and non-tumoral components of the tumor immune microenvironment (TIME) play a significant role in cancer growth. Therefore, developing novel and focused therapy for ovarian cancer is critical. Studies indicate that TIME is involved in developing ovarian cancer, particularly genome-, transcriptome-, and proteome-wide studies. As a result, TIME may present a prospective therapeutic target for ovarian cancer patients.</p><p><strong>Areas covered: </strong>We examined several TIME-targeting medicines and the connection between TIME and ovarian cancer. The key protagonists and events in the TIME and therapeutic strategies that explicitly target these events in ovarian cancer are discussed.</p><p><strong>Expert opinion: </strong>We highlighted various targeted therapies against TIME in ovarian cancer, including anti-angiogenesis therapies and immune checkpoint inhibitors. While these therapies are in their infancy, they have shown promise in controlling ovarian cancer progression. The use of 'omics' technology is helping in better understanding of TIME in ovarian cancer and potentially identifying new therapeutic targets. TIME-targeted strategies could account for an additional treatment strategy when treating ovarian cancer.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10358825","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":"An overview of novel antimicrobial carbonic anhydrase inhibitors.","authors":"Claudiu T Supuran","doi":"10.1080/14728222.2023.2263914","DOIUrl":"10.1080/14728222.2023.2263914","url":null,"abstract":"<p><strong>Introduction: </strong>Four different genetic families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) are present in bacteria, α-, β-, γ- and ι-CAs. They play relevant functions related to CO<sub>2</sub>, HCO<sub>3</sub><sup>-</sup>/H<sup>+</sup> ions homeostasis, being involved in metabolic biosynthetic pathways, pH regulation, and represent virulence and survival factors for bacteria in various niches. Bacterial CAs started to be considered druggable targets in the last decade, as their inhibition impairs survival, growth, and virulence of these pathogens.</p><p><strong>Areas covered: </strong>Significant advances were registered in the last years for designing effective inhibitors of sulfonamide type for <i>Helicobacter pylori</i> α-CA, <i>Neisseria gonorrhoeae</i> α-CA, vacomycin-resistant enterococci (VRE) α- and γ-CAs, for which the in vivo validation has also been achieved. MIC-s in the range of 0.25-4.0 µg/mL for wild type and drug resistant <i>N. gonorrhoeae</i> strains, and of 0.007-2.0 µg/mL for VRE were observed for some 1,3,4-thiadiazole-2-sulfonamides, and acetazolamide was effective in gut decolonization from VRE.</p><p><strong>Expert opinion: </strong>Targeting bacterial CAs from other pathogens, among which <i>Vibrio cholerae</i>, <i>Mycobacterium tuberculosis</i>, <i>Brucella suis</i>, <i>Salmonella enterica</i> serovar Typhimurium, <i>Legionella pneumophila</i>, <i>Porphyromonas gingivalis</i>, <i>Clostridium perfringens</i>, <i>Streptococcus mutans</i>, <i>Burkholderia pseudomallei</i>, <i>Francisella tularensis</i>, <i>Escherichia coli</i>, <i>Mammaliicoccus (Staphylococcus) sciuri</i>, <i>Pseudomonas aeruginosa</i>, may lead to novel antibacterials devoid of drug resistance problems.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41137642","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}
Temugin Berta, Judith A Strong, Jun-Ming Zhang, Ru-Rong Ji
{"title":"Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain: an update.","authors":"Temugin Berta, Judith A Strong, Jun-Ming Zhang, Ru-Rong Ji","doi":"10.1080/14728222.2023.2247563","DOIUrl":"10.1080/14728222.2023.2247563","url":null,"abstract":"<p><strong>Introduction: </strong>Current treatments for chronic pain are inadequate. Here, we provide an update on the new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain.</p><p><strong>Areas covered: </strong>Despite the complex nature of chronic pain and its underlying mechanisms, we do know that changes in the plasticity and modality of neurons in DRGs play a pivotal role. DRG neurons are heterogenous and offer potential pain targets for different therapeutic interventions. We discuss the last advancements of these interventions, which include the use of systemic and local administrations, selective nerve drug delivery, and gene therapy. In particular, we provide updates and further details on the molecular characterization of primary sensory neurons, new analgesics entering the market, and future gene therapy approaches.</p><p><strong>Expert opinion: </strong>DRGs and primary sensory neurons are promising targets for chronic pain treatment due to their key role in pain signaling, unique anatomical location, and the potential for different targeted therapeutic interventions.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10028913","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}
Mario Manto, Jan Cendelin, Michael Strupp, Hiroshi Mitoma
{"title":"Advances in cerebellar disorders: pre-clinical models, therapeutic targets, and challenges.","authors":"Mario Manto, Jan Cendelin, Michael Strupp, Hiroshi Mitoma","doi":"10.1080/14728222.2023.2263911","DOIUrl":"10.1080/14728222.2023.2263911","url":null,"abstract":"<p><strong>Introduction: </strong>Cerebellar ataxias (CAs) represent neurological disorders with multiple etiologies and a high phenotypic variability. Despite progress in the understanding of pathogenesis, few therapies are available so far. Closing the loop between preclinical studies and therapeutic trials is important, given the impact of CAs upon patients' health and the roles of the cerebellum in multiple domains. Because of a rapid advance in research on CAs, it is necessary to summarize the main findings and discuss future directions.</p><p><strong>Areas covered: </strong>We focus our discussion on preclinical models, cerebellar reserve, the therapeutic management of CAs, and suitable surrogate markers. We searched Web of Science and PubMed using keywords relevant to cerebellar diseases, therapy, and preclinical models.</p><p><strong>Expert opinion: </strong>There are many symptomatic and/or disease-modifying therapeutic approaches under investigation. For therapy development, preclinical studies, standardization of disease evaluation, safety assessment, and demonstration of clinical improvements are essential. Stage of the disease and the level of the cerebellar reserve determine the goals of the therapy. Deficits in multiple categories and heterogeneity of CAs may require disease-, stage-, and symptom-specific therapies. More research is needed to clarify how therapies targeting the cerebellum influence both basal ganglia and the cerebral cortex, poorly explored domains in CAs.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41096849","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":"Pleural mesothelioma: a snapshot of emerging drug targets and opportunities for non-surgical therapeutic advancement.","authors":"Jean-Baptiste Assié, Didier Jean","doi":"10.1080/14728222.2023.2277224","DOIUrl":"10.1080/14728222.2023.2277224","url":null,"abstract":"<p><strong>Introduction: </strong>Pleural mesothelioma is a rare and aggressive cancer originating in the pleura, with a devastating prognosis and limited treatment options. There have been significant advancements in the management of this disease in recent years. Since 2021, nivolumab and ipilimumab immune checkpoint inhibitors have become the new standard of care for first-line treatment of pleural mesothelioma.</p><p><strong>Areas covered: </strong>While a combination of chemotherapy and immune checkpoint inhibitors appears to be the next step, targeted therapies are emerging thanks to our understanding of the oncogenesis of pleural mesothelioma. Moreover, several new strategies are currently being investigated, including viral therapy, antibody-drug conjugates, and even cell therapies with CAR-T cells or dendritic cells. In this review, we will explore the various future opportunities that could potentially transform patients' lives in light of the clinical trials that have been conducted.</p><p><strong>Expert opinion: </strong>Future clinical studies aim to rebiopsy patients after disease progression to identify new molecular alterations and to be associated with ancillary studies, guiding subsequent therapy decisions. Predicting and investigating treatment resistance mechanisms will lead to innovative approaches and improved treatment outcomes.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411173","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}
Wenqiang Zhang, Qiwei Nie, Xuling Zhang, Long Huang, Guofu Pang, Jing Chu, Xiaoxu Yuan
{"title":"miR-26a-5p restoration <i>via</i> EZH2 silencing blocks the IL-6/STAT3 axis to repress the growth of prostate cancer.","authors":"Wenqiang Zhang, Qiwei Nie, Xuling Zhang, Long Huang, Guofu Pang, Jing Chu, Xiaoxu Yuan","doi":"10.1080/14728222.2023.2293750","DOIUrl":"10.1080/14728222.2023.2293750","url":null,"abstract":"<p><strong>Background: </strong>Interleukin-6 (IL-6) is involved in the activation of several oncogenic pathways in prostate cancer. However, its upstream trans-signaling pathway remains largely unknown. This work proposes a mechanistic explanation of IL-6's upstream effectors in prostate carcinogenesis.</p><p><strong>Research design & methods: </strong>Samples were harvested to validate the expression of EZH2, miR-26a-5p, and IL-6. Moreover, the protein and its phosphorylation of STAT3 (signal transducer and transcription activator 3) were assessed in prostate cancer cells. We explored the effects of these effectors on malignant phenotypes in vitro and tumor growth in vivo using functional assays. Bioinformatics analysis, dual-luciferase reporter gene assays, and chromatin immunoprecipitation (ChIP) assays were used to determine their binding relationships.</p><p><strong>Results: </strong>Overexpression of EZH2 and IL-6, and under expression of miR-26a-5p was observed in prostate cancer. Silencing IL-6 repressed STAT3 to suppress the malignant phenotypes of prostate cancer cells. Mechanistically, EZH2 inhibited miR-26a-5p expression by promoting H3K27 histone methylation, and miR-26a-5p restricted the malignant phenotypes of prostate cancer by targeting IL-6. Ectopic EZH2 expression reduced xenograft growth by inhibiting miR-26a-5p and activating the IL-6/STAT3 axis.</p><p><strong>Conclusion: </strong>EZH2 May potentially be involved in regulating its expression by recruiting H3K27me3 to the miR-26a-5p promoter region, which could further impact the IL6/STAT3 pathway.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058265","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":"Targeting cyclin-dependent kinases in rheumatoid arthritis and psoriasis - a review of current evidence.","authors":"Marzena Staniszewska, Kajetan Kiełbowski, Klaudia Rusińska, Estera Bakinowska, Ewa Gromowska, Andrzej Pawlik","doi":"10.1080/14728222.2023.2285784","DOIUrl":"10.1080/14728222.2023.2285784","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with synovial proliferation and bone erosion, which leads to the structural and functional impairment of the joints. Immune cells, together with synoviocytes, induce a pro-inflammatory environment and novel treatment agents target inflammatory cytokines. Psoriasis is a chronic immune-mediated skin disease, and several cytokines are considered as typical mediators in the progression of the disease, including IL-23, IL-22, and IL-17, among others.</p><p><strong>Area covered: </strong>In this review, we try to evaluate whether cyclin-dependent kinases (CDK), enzymes that regulate cell cycle and transcription of various genes, could become novel therapeutic targets in RA and psoriasis. We present the main results of in vitro and in vivo studies, as well as scarce clinical reports.</p><p><strong>Expert opinion: </strong>CDK inhibitors seem promising for treating RA and psoriasis because of their multidirectional effects. CDK inhibitors may affect not only the process of osteoclastogenesis, thereby reducing joint destruction in RA, but also the process of apoptosis of neutrophils and macrophages responsible for the development of inflammation in both RA and psoriasis. However, assessing the efficacy of these drugs in clinical practice requires multi-center, long-term clinical trials evaluating the effectiveness and safety of CDK-blocking therapy in RA and psoriasis.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138046676","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 M Ferrario, Sarfaraz Ahmad, Robert Speth, Louis J Dell'Italia
{"title":"Is chymase 1 a therapeutic target in cardiovascular disease?","authors":"Carlos M Ferrario, Sarfaraz Ahmad, Robert Speth, Louis J Dell'Italia","doi":"10.1080/14728222.2023.2247561","DOIUrl":"10.1080/14728222.2023.2247561","url":null,"abstract":"<p><strong>Introduction: </strong>Non-angiotensin converting enzyme mechanisms of angiotensin II production remain underappreciated in part due to the success of current therapies to ameliorate the impact of primary hypertension and atherosclerotic diseases of the heart and the blood vessels. This review scrutinize the current literature to highlight chymase role as a critical participant in the pathogenesis of cardiovascular disease and heart failure.</p><p><strong>Areas covered: </strong>We review the contemporaneous understanding of circulating and tissue biotransformation mechanisms of the angiotensins focusing on the role of chymase as an alternate tissue generating pathway for angiotensin II pathological mechanisms of action.</p><p><strong>Expert opinion: </strong>While robust literature documents the singularity of chymase as an angiotensin II-forming enzyme, particularly when angiotensin converting enzyme is inhibited, this knowledge has not been fully recognized to clinical medicine. This review discusses the limitations of clinical trials' that explored the benefits of chymase inhibition in accounting for the failure to duplicate in humans what has been demonstrated in experimental animals.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030495","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}