Kanika Jain, Tarun Tyagi, Sean X Gu, E Vincent S Faustino, John Hwa
{"title":"Demographic diversity in platelet function and response to antiplatelet therapy.","authors":"Kanika Jain, Tarun Tyagi, Sean X Gu, E Vincent S Faustino, John Hwa","doi":"10.1016/j.tips.2024.11.005","DOIUrl":"10.1016/j.tips.2024.11.005","url":null,"abstract":"<p><p>Recent studies have highlighted the complexity of platelet biology, revealing their diverse roles beyond hemostasis. Pathological platelet activation is now recognized as a key contributor to thrombosis and inflammation that are both central to cardiovascular disease (CVD). Emerging research emphasizes the significant impact of demographic factors - such as age, sex, race, and ethnicity - on CVD risk and responses to antiplatelet therapies. These population-based differences, shaped by genetic and non-genetic factors, highlight the need for reevaluation of antiplatelet strategies. We address current knowledge and emphasize the pressing need for further research into platelet biology and cardiovascular outcomes across diverse populations. In this review we advocate for tailored therapeutic approaches in CVD based on the recent demographic-focused findings.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"78-93"},"PeriodicalIF":13.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11710996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic targeting of exportin-1 beyond nuclear export.","authors":"Yi Fan Chen, Drew J Adams","doi":"10.1016/j.tips.2024.11.002","DOIUrl":"10.1016/j.tips.2024.11.002","url":null,"abstract":"<p><p>Exportin-1 (XPO1), also known as chromosome region maintenance 1 (CRM1), directly binds to and mediates the nuclear export of hundreds of cargo proteins. Blocking nuclear export by the selective inhibitors of nuclear export (SINEs) is a validated therapeutic axis in cancer and an active area of research. However, a growing body of evidence implicates XPO1 in biological functions beyond nuclear export that include the regulation of mitosis and the epigenome. Additionally, new pharmacological classes of small molecules have emerged that degrade XPO1 or induce distinct cellular activity profiles. Here, we discuss the canonical model of nuclear export and XPO1's emergence as an anticancer target. We also spotlight the key evidence for underappreciated XPO1 functions and discuss the use of chemical probes to uncover new cellular roles for XPO1. With these growing trends, the field is poised to extend XPO1 therapeutic targeting to indications beyond oncology.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"20-31"},"PeriodicalIF":13.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging therapeutic strategies for optic nerve regeneration.","authors":"Qi Zhang, Jiahui Tang, Liyan Liu, Zhe Liu, Jingfei Xue, Jian Ge, Yehong Zhuo, Yiqing Li","doi":"10.1016/j.tips.2024.11.008","DOIUrl":"10.1016/j.tips.2024.11.008","url":null,"abstract":"<p><p>The optic nerve, comprising axons from retinal ganglion cells (RGCs), is a component of the central nervous system (CNS) that generally exhibits a limited regeneration capacity following injury in mature mammals, resulting in permanent vision loss. Here, we summarize recent advances in interventions targeting cell-intrinsic and cell-extrinsic mechanisms to enhance RGC axon regeneration. Additionally, we summarize strategies for guiding the reconnection of regenerating axons with brain visual targets, aiming to restore partial visual function. Given the advent of high-throughput screening techniques and multiomics analyses, we discuss how these emerging methodologies deepen our understanding of regenerative mechanisms and expedite the development of innovative therapeutic approaches. Lastly, we explore the translational potential of these strategies in achieving clinically meaningful vision recovery.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"45-61"},"PeriodicalIF":13.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ACK1/TNK2 kinase: molecular mechanisms and emerging cancer therapeutics.","authors":"Dhivya Sridaran, Nupam P Mahajan","doi":"10.1016/j.tips.2024.11.006","DOIUrl":"10.1016/j.tips.2024.11.006","url":null,"abstract":"<p><p>Activated CDC42-associated kinase 1 (ACK1), encoded by the TNK2 gene, is a cytoplasmic non-receptor tyrosine kinase whose aberrant activation correlates positively with cancer severity. Recent research has revealed the functional relevance of this oncokinase - it is an epigenetic regulator that drives cancer progression in multiple malignancies. Although ACK1 is an attractive target for therapeutic intervention, incomplete knowledge of its diverse signaling mechanisms and the lack of specific inhibitors have challenged its clinical success. We summarize recent breakthroughs in understanding ACK1 regulation and cellular signaling, and shed light on its immunomodulatory role in balancing T cell activation. We provide a comprehensive overview of preclinical, proof-of-concept studies of potent ACK1-targeting small-molecule inhibitors that are expected to enter clinical trials for cancer patients.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"62-77"},"PeriodicalIF":13.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Poxvirus vaccines: the evolution of an 18th-century vaccine to the 21st century.","authors":"Yuhong Xiao, Stuart N Isaacs","doi":"10.1016/j.tips.2024.10.015","DOIUrl":"10.1016/j.tips.2024.10.015","url":null,"abstract":"<p><p>The unprecedented global spread of monkeypox (mpox) has reinvigorated the pursuit of next-generation poxvirus vaccines. Given the success of the mRNA-lipid nanoparticle (LNP) vaccine platform to vaccinate against SARS-CoV-2, candidate poxvirus mRNA vaccines, as recently reported by Zuiani et al. and Mucker et al., demonstrate success in nonhuman primate (NHP) models and provide insights into the basis of the protective immune response.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1086-1088"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucy H R Whitaker, Clive Page, Charles Morgan, Andrew W Horne, Philippa T K Saunders
{"title":"Endometriosis: cannabidiol therapy for symptom relief.","authors":"Lucy H R Whitaker, Clive Page, Charles Morgan, Andrew W Horne, Philippa T K Saunders","doi":"10.1016/j.tips.2024.10.014","DOIUrl":"10.1016/j.tips.2024.10.014","url":null,"abstract":"<p><p>Endometriosis is a common, chronic, incurable condition the hallmark of which is the presence of lesions (tissue resembling endometrium) in sites outside the womb, with symptoms including chronic debilitating pain and fatigue. However, current therapeutic options are limited. Recent advances in our understanding of the mechanisms that contribute to the development of lesions and pain experience in endometriosis as well as surveys of patients have increased interest in testing recently approved formulations containing cannabidiol (CBD) in this patient group. In this review, we summarise data from patient samples and animals models focussed on the pathophysiology of endometriosis, including pathways where CBD has activity. We consider the available formulations of CBD-containing products, their pharmacokinetics (PK), and their use in ongoing clinical trials in endometriosis and other pain conditions.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1150-1161"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pegcetacoplan (Syfovre<sup>ΤΜ</sup>): targeting complement C3 in geographic atrophy.","authors":"Dimitrios C Mastellos, John D Lambris","doi":"10.1016/j.tips.2024.10.001","DOIUrl":"10.1016/j.tips.2024.10.001","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1175-1176"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexios-Fotios A Mentis, Helen W Hernandez, Kenneth I Kaitin
{"title":"Drug repurposing for neglected and zoonotic diseases.","authors":"Alexios-Fotios A Mentis, Helen W Hernandez, Kenneth I Kaitin","doi":"10.1016/j.tips.2024.10.012","DOIUrl":"10.1016/j.tips.2024.10.012","url":null,"abstract":"<p><p>Globalization and climate change have intensified the need to address the marginalization of R&D for neglected and zoonotic diseases. We propose that drug repurposing, using enabling technologies such as artificial intelligence, can address this need at a lower cost than de novo R&D processes.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1100-1103"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ari Joffe, Nancy Vázquez-Maldonado, Kentner L Singleton, Wolfgang W Leitner
{"title":"Tiny but mighty: small molecules as vaccine adjuvants.","authors":"Ari Joffe, Nancy Vázquez-Maldonado, Kentner L Singleton, Wolfgang W Leitner","doi":"10.1016/j.tips.2024.10.011","DOIUrl":"10.1016/j.tips.2024.10.011","url":null,"abstract":"<p><p>Screening small molecule (SM) libraries now replaces traditional methods for vaccine adjuvant discovery. A study by Soni et al. highlights the use of primary human cells in high-throughput screening (HTS), leading to the discovery of a novel SM TLR7/8 agonist, PVP-037. This compound successfully restored vaccine-induced immune responses in aged mice.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1097-1099"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Some assembly required: a single-RNA vaccine against enterovirus-D68.","authors":"Noah Pollack, William T Jackson","doi":"10.1016/j.tips.2024.10.010","DOIUrl":"10.1016/j.tips.2024.10.010","url":null,"abstract":"<p><p>A single-RNA-based vaccine against enterovirus-D68, a respiratory virus and causative agent of severe paralytic disease in children, by the Erasmus group shows great promise in generating broadly cross-neutralizing antibodies in mice and macaque models of infection.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1089-1091"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}