Current Opinion in Pharmacology最新文献

{"title":"Editorial overview: Advanced therapies and new targets in ocular diseases","authors":"Claudio Bucolo, Chiara M. Eandi, Sanjoy K. Bhattacharya","doi":"10.1016/j.coph.2025.102543","DOIUrl":"10.1016/j.coph.2025.102543","url":null,"abstract":"","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102543"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in 3D-printed transdermal microneedle patches for antifungal therapy: Current scenario and challenges","authors":"Sarang Sunil Mahamuni ,&nbsp;Madhuri Mahesh Desai ,&nbsp;Koustubh Mansing Thorawades ,&nbsp;Durgacharan A. Bhagwat","doi":"10.1016/j.coph.2025.102545","DOIUrl":"10.1016/j.coph.2025.102545","url":null,"abstract":"<div><div>Skin fungal infection and systemic fungal infections are highly prevalent, causing significant healthcare burden. Addressing the pervasive and sometimes life-threatening nature of fungal infections has spurred extensive research into novel therapeutic strategies, particularly focusing on effective drug formulations and innovative delivery routes. Among this transdermal drug delivery (TDD) using microneedles (MNs) is a promising approach. 3D-printed MN patches are composed of arrays of tiny, needle-like structures engineered to facilitate the delivery of therapeutic agents by breaching the stratum corneum. Using the precision of 3D printing and improved drug delivery of MNs, 3D-printed transdermal MNs present a promising approach to manage fungal infections. This review provides a comprehensive analysis of recent literature on the use of 3D-printed MNs for antifungal therapy, emphasizing advancements in fabrication methods, drug incorporation techniques, and preclinical assessment outcomes. Furthermore, the study informs on various novel innovations employing antifungal agent administered through transdermal patches, demonstrating their efficacy and superiority over traditional methods. The majority of the studies are <em>in vitro</em> experimental studies, highlighting the need for human trials to translate 3D-printed MN-based TDD into clinical practice. The findings highlight the promise of 3D-printed microneedle patches in transforming transdermal antifungal therapy; however, extensive clinical validation remains crucial for regulatory endorsement and practical implementation.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102545"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transdermal delivery of antibacterial peptides in the management of methicillin-resistant Staphylococcus aureus","authors":"Shivraj Sangappa Shivpuje ,&nbsp;Durgacharan A. Bhagwat ,&nbsp;Pankaj Ashok Jadhav ,&nbsp;Kimaya P. Joshi ,&nbsp;Suraj N. Mali","doi":"10.1016/j.coph.2025.102548","DOIUrl":"10.1016/j.coph.2025.102548","url":null,"abstract":"<div><div>Bacterial antimicrobial resistance (AMR) is of major public concern around the globe that arises when bacteria which earlier responded to the antibiotic therapy no longer respond to the same therapy and become resistant. The AMR has emerged due to the antibiotic abuse resulting in the development of multidrug-resistant (MDR) bacteria including methicillin-resistant <em>Staphylococcus aureus</em> (MRSA). The conventional antibiotics including vancomycin have nowadays become ineffective due to the gradual evolution and adaptation of bacteria to the surrounding environment. Antimicrobial peptides (AMPs) have emerged as an effective therapeutic option for the treatment of MRSA-induced skin and soft tissue infections (SSTIs). They offer broad-spectrum antibacterial activity with lower probability of drug resistance development. However, these AMPs face limitations such as proteolytic degradation, poor bioavailability, and potential cytotoxicity limiting their efficacy in clinical settings. Transdermal drug delivery platforms, including microneedles (MNs) coupled with the nano-formulations, have been developed to improve the AMP stability, bioavailability, and targeted release to avoid off-target cytotoxicity. Innovative strategies including Janus-type antibacterial dressings, bioresponsive MNs, and metal–organic frameworks (MOFs)-based nanocarriers have shown favorable results against the MRSA-induced skin infection. Numerous naturally occurring and synthetic antibacterial biopeptides and a Food and Drug Administration–approved glycopeptide, vancomycin, exhibited improved biofilm penetration and therapeutic efficacy when combined with smart MNs and nanosystems. Despite these improvements, challenges associated with AMP stability, cytotoxicity, and manufacturing costs still remain that limit its clinical translation. This review discussed the various MN-assisted deliveries of AMPs and associated challenges for the treatment of MRSA infections.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102548"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balancing genome integrity and carcinogenesis: Insights into DNA damage response, repair pathways, and cancer therapies","authors":"Sudha Sharma,&nbsp;Srijita Dhar,&nbsp;Sagar Sengupta","doi":"10.1016/j.coph.2025.102522","DOIUrl":"10.1016/j.coph.2025.102522","url":null,"abstract":"","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102522"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic hurdles in acute myeloid leukemia: Leukemic stem cells, inflammation and immune dysfunction","authors":"Bofei Wang ,&nbsp;Patrick K. Reville ,&nbsp;Hussein A. Abbas","doi":"10.1016/j.coph.2025.102526","DOIUrl":"10.1016/j.coph.2025.102526","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is an aggressive and highly heterogeneous hematological malignancy characterized by clonal expansion and differentiation arrest in myeloid progenitor cells. Despite advancements in chemotherapy, allogeneic hematopoietic stem cell transplantation, and post-remission maintenance therapies, the long-term survival remains unsatisfactory with high rates of relapse and refractory. These therapeutic challenges are mediated by multiple factors, including the complexity of the cellular hierarchies in AML, the interaction of leukemic stem cells (LSCs) with the bone marrow niche, inflammation, and immune evasion mechanisms. Further, the absence of specific surface markers that distinguish LSCs from normal hematopoietic stem cells, together with LSCs’ functional heterogeneity, complicates targeted treatment approaches. Immune dysfunction, including T cell exhaustion and immune suppression within the bone marrow niche contributes to therapy resistance. In this brief review, we aim to explore current challenges in AML therapy, focusing on LSC-driven resistance, immune evasion, and the need for innovative therapeutic strategies.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102526"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipids and lipid regulators in intraocular pressure homeostasis","authors":"Gregory T. Rognon ,&nbsp;Anna Yu-an Liao ,&nbsp;Rodahina Philihina Pasteurin ,&nbsp;Avinash Soundararajan ,&nbsp;Padmanabhan Paranji Pattabiraman","doi":"10.1016/j.coph.2025.102523","DOIUrl":"10.1016/j.coph.2025.102523","url":null,"abstract":"<div><div>Increased intraocular pressure is the strongest correlated modifiable risk factor for developing primary open-angle glaucoma (POAG). Lipids have long been known to be a major constituent of aqueous humor. Lipid mediators, prostaglandins for example, are the first-line treatment for glaucoma. Innovative technologies have made the investigation of lipids in small quantities possible, and interest in identifying lipids as new pharmacological targets has grown in ophthalmology. There is expanding evidence to suggest that lipids and their active metabolites play a role in POAG pathophysiology, as differences between control and diseased eyes have now been demonstrated. The role of these differences is yet to be determined and is the subject of this review.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102523"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies to enhance anti-leukaemia immunotherapy","authors":"Memnon Lysandrou,&nbsp;Robert Zeiser","doi":"10.1016/j.coph.2025.102525","DOIUrl":"10.1016/j.coph.2025.102525","url":null,"abstract":"<div><div>Acute myeloid leukaemia (AML) was an incurable disease prior to allogeneic haematopoietic cell transplantation (allo-HCT), which was proven to be a potent cellular immunotherapy-approach. However, allo-HCT has major side effects, with disease relapse presenting as a frequent complication. Novel immunotherapies aim to reduce toxicity and increase the anti-leukaemia activity of allo-HCT. Technological advancements in genetic engineering approaches enable potent immunotherapeutic activity while limiting toxicities. A biology-driven application of small molecules that target AML vulnerabilities holds promise to enhance anti-leukaemia immunotherapy. Extensive preclinical testing of these approaches is essential to reduce toxicity and to find the ideal combination partners for future clinical testing.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102525"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel approaches to CAR T cell target identification in acute myeloid leukemia","authors":"Gordon Victor Hoffmann ,&nbsp;Adrian Gottschlich ,&nbsp;Marion Subklewe ,&nbsp;Sebastian Kobold","doi":"10.1016/j.coph.2025.102524","DOIUrl":"10.1016/j.coph.2025.102524","url":null,"abstract":"<div><div>Identifying safe and effective CAR T cell targets in acute myeloid leukemia (AML) is challenging due to the disease’s complexity and overlap with normal hematopoiesis. This review highlights advances in target discovery for AML, emphasizing innovative approaches. Structural surfaceomics identifies tumor-specific protein conformations, while AI-driven single-cell RNA sequencing integrates multi-source data to pinpoint optimal targets. Refined cell surface capture technology maps the AML surfaceome without relying on predefined antibodies. These strategies enhance CAR T cell specificity and minimize off-tumor effects, offering promising pathways for safer and more effective AML treatments and broader cancer therapies.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102524"},"PeriodicalIF":4.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncohistone-sculpted epigenetic mechanisms in pediatric brain cancer","authors":"Deo Prakash Pandey ,&nbsp;Kumar Somyajit","doi":"10.1016/j.coph.2025.102505","DOIUrl":"10.1016/j.coph.2025.102505","url":null,"abstract":"<div><div>Chromatin dynamics, involving reversible changes in chromatin structure, shape key cellular processes and genomic integrity during development and proliferation, with disruptions leading to cancer. Histones, core components of chromatin and substrates for chromatin-modifying enzymes, play crucial roles in oncogenesis when misregulated or mutated. This is particularly pronounced in pediatric hind brain cancers, some of which are driven primarily by the oncohistone H3K27M and the recently identified oncohistone-mimic protein CXorf67/EZHIP. Notably, H3K27M and EZHIP-driven cancers exhibit low mutation burdens, highlighting the enigmatic role of non-mutational epigenetic reprogramming in oncogenesis beyond traditional paradigms of oncogene activation and tumor suppressor loss. Here, we review the impact of H3K27M and EZHIP-driven cancer mechanisms on chromatin and transcriptional dysregulation leading to aberrant cell fate determination, and their potential influence beyond gene activity, affecting broader cellular pathways. Illuminating these mechanisms is crucial for advancing treatment options for pediatric brain cancers, where therapeutic regimens are poorly defined.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"81 ","pages":"Article 102505"},"PeriodicalIF":4.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Message from the New Editor-in-Chief, Prof. Sheng-Tao Hou","authors":"Sheng-Tao Hou","doi":"10.1016/j.coph.2024.102504","DOIUrl":"10.1016/j.coph.2024.102504","url":null,"abstract":"","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"80 ","pages":"Article 102504"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}