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Trends in pharmacological sciences最新文献

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Advances in cell therapy: progress and challenges in hematological and solid tumors. 细胞疗法的进展：血液肿瘤和实体瘤的进展与挑战。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-12-01 Epub Date: 2024-11-27 DOI: 10.1016/j.tips.2024.10.016
Claudia D'Avanzo, Franziska Blaeschke, Memnon Lysandrou, Florian Ingelfinger, Robert Zeiser
{"title":"Advances in cell therapy: progress and challenges in hematological and solid tumors.","authors":"Claudia D'Avanzo, Franziska Blaeschke, Memnon Lysandrou, Florian Ingelfinger, Robert Zeiser","doi":"10.1016/j.tips.2024.10.016","DOIUrl":"10.1016/j.tips.2024.10.016","url":null,"abstract":"<p><p>Cell-based therapies harness the endogenous ability of the immune system to fight cancer and have shown promising results in the treatment of hematological malignancies. However, their clinical application beyond B cell malignancies is hampered by numerous hurdles, ranging from relapsed disease to a hostile tumor microenvironment (TME). Recent advances in cell engineering and TME modulation may expand the applicability of these therapies to a wider range of cancers, creating new treatment possibilities. Breakthroughs in advanced gene editing and sophisticated cell engineering, have also provided promising solutions to longstanding challenges. In this review, we examine the challenges and future directions of the most prominent cell-based therapies, including chimeric antigen receptor (CAR)-T cells, tumor-infiltrating lymphocytes (TILs), and natural killer (NK) cells, and emerging modalities. We provide a comprehensive analysis of emerging cell types and combination strategies translated into clinical trials, offering insights into the next generation of cell-based cancer treatments.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1119-1134"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740793","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}
引用次数: 0
Strategies to boost antibody selectivity in oncology. 提高肿瘤中抗体选择性的策略。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-12-01 Epub Date: 2024-11-29 DOI: 10.1016/j.tips.2024.10.005
Vincent Blay, Atanasio Pandiella
{"title":"Strategies to boost antibody selectivity in oncology.","authors":"Vincent Blay, Atanasio Pandiella","doi":"10.1016/j.tips.2024.10.005","DOIUrl":"10.1016/j.tips.2024.10.005","url":null,"abstract":"<p><p>Antibodies in oncology are being equipped with toxic cargoes and effector functions that can kill cells at very low concentrations. A key challenge is that most targets on cancer cells are also present on at least some healthy cells. Shared targets can result in off-tumor binding and compromise the safety and potential of therapeutic candidates. In this review, we survey strategies that can help direct biologics to cancer sites more selectively. These strategies are becoming increasingly feasible thanks to advances in molecular design and engineering. The objective is to create therapeutics that exploit changes in cancer and leverage the human body infrastructure, enabling therapeutics that discriminate not just self from non-self but diseased from healthy tissue.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1135-1149"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751763","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}
引用次数: 0
Development of PROTACs using computational approaches. 利用计算方法开发 PROTAC。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-12-01 Epub Date: 2024-11-19 DOI: 10.1016/j.tips.2024.10.006
Jingxuan Ge, Chang-Yu Hsieh, Meijing Fang, Huiyong Sun, Tingjun Hou
{"title":"Development of PROTACs using computational approaches.","authors":"Jingxuan Ge, Chang-Yu Hsieh, Meijing Fang, Huiyong Sun, Tingjun Hou","doi":"10.1016/j.tips.2024.10.006","DOIUrl":"10.1016/j.tips.2024.10.006","url":null,"abstract":"<p><p>Proteolysis-targeting chimeras (PROTACs) are drugs designed to degrade target proteins via the ubiquitin-proteasome system. With the application of computational biology/chemistry technique in drug design, numerous computer-aided drug design and artificial intelligence (AI)-driven drug design (CADD/AIDD) methods have recently emerged to facilitate the development of PROTAC drugs. We systematically review the role of in silico tools in PROTAC drug design, emphasizing how computational software can model PROTAC action and structure, predict activity, and assist in molecule design. We also discuss current challenges in the rational design of PROTACs from an in silico perspective, such as deviations from small-molecule druggability and the limited availability of training data. We provide an overview of recent discoveries and emerging research in this field, and discuss their potential impact on PROTAC design strategies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1162-1174"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682492","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}
引用次数: 0
Challenges and considerations in multi-epitope vaccine design surrounding toll-like receptors. 围绕收费样受体设计多表位疫苗的挑战和考虑因素。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-12-01 Epub Date: 2024-11-26 DOI: 10.1016/j.tips.2024.10.013
Masaud Shah, Sobia Rafiq, Hyun G Woo
{"title":"Challenges and considerations in multi-epitope vaccine design surrounding toll-like receptors.","authors":"Masaud Shah, Sobia Rafiq, Hyun G Woo","doi":"10.1016/j.tips.2024.10.013","DOIUrl":"10.1016/j.tips.2024.10.013","url":null,"abstract":"<p><p>Epitope-based peptide vaccines elicit targeted immune responses, making them effective for diseases requiring focused immune activation, such as targeting cancer-associated antigens. Strategies like peptide cocktails and mRNA-based epitope vaccines have revolutionized the field; however, the term 'multi-epitope peptide vaccine' has been overextended, especially concerning the use of toll-like receptors (TLRs), their ligands, and peptide linkers. TLRs are often conflated with T cell receptors (TCRs) and B cell receptors (BCRs), which recognize immunogenic peptides within vaccines. This Opinion clarifies the role of TLRs and highlights challenges linked to their indiscriminate use in multi-epitope vaccine design. While peptide linkers are crucial in creating multivalent vaccines, their unsupervised application is increasing and warrants attention. After highlighting their role in advancing peptide vaccines, we discuss critical factors in linker implementation and caution against their misuse, which could undermine vaccines' efficacy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1104-1118"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740794","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}
引用次数: 0
RH5 antigenic landscape shapes vaccine and antibody development. RH5 抗原结构影响疫苗和抗体的开发。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-12-01 Epub Date: 2024-11-06 DOI: 10.1016/j.tips.2024.10.008
Palak N Patel, Niraj H Tolia
{"title":"RH5 antigenic landscape shapes vaccine and antibody development.","authors":"Palak N Patel, Niraj H Tolia","doi":"10.1016/j.tips.2024.10.008","DOIUrl":"10.1016/j.tips.2024.10.008","url":null,"abstract":"<p><p>The essential interaction between Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) and basigin makes RH5 a prime target for broadly neutralizing antibodies. A recent study by Barrett et al. mapped the RH5 antigenic landscape from RH5.1/AS01<sub>B</sub> vaccinees and identified a potent public antibody clonotype, advancing malaria vaccine and prophylactic antibody development.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1092-1094"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606220","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}
引用次数: 0
Recent advancements in vaccine research and development. 疫苗研发的最新进展。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-12-01 Epub Date: 2024-11-27 DOI: 10.1016/j.tips.2024.11.004
Jerry C Madukwe
{"title":"Recent advancements in vaccine research and development.","authors":"Jerry C Madukwe","doi":"10.1016/j.tips.2024.11.004","DOIUrl":"10.1016/j.tips.2024.11.004","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1083-1085"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751758","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}
引用次数: 0
Targeting dendritic cells to drive PDAC immunotherapy response. 靶向树突状细胞驱动 PDAC 免疫疗法反应。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-12-01 Epub Date: 2024-11-06 DOI: 10.1016/j.tips.2024.10.009
Alyssa G Weinstein, David G DeNardo
{"title":"Targeting dendritic cells to drive PDAC immunotherapy response.","authors":"Alyssa G Weinstein, David G DeNardo","doi":"10.1016/j.tips.2024.10.009","DOIUrl":"10.1016/j.tips.2024.10.009","url":null,"abstract":"<p><p>Pancreatic adenocarcinoma (PDAC) has been historically unresponsive to immunotherapy, predominantly due to lower antigen loads and a lack of tumor-infiltrating dendritic cells (DCs) and T cells. A recent study by Mahadevan and colleagues demonstrates that increasing DC infiltration through use of an engineered DC1 vaccine can sensitize PDAC to immunotherapy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1095-1096"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606177","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}
引用次数: 0
Neutrophil extracellular traps in wound healing. 伤口愈合过程中的中性粒细胞胞外捕获器
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI: 10.1016/j.tips.2024.09.007
Zhanyong Zhu, Shengzhi Zhou, Sicheng Li, Song Gong, Qi Zhang
{"title":"Neutrophil extracellular traps in wound healing.","authors":"Zhanyong Zhu, Shengzhi Zhou, Sicheng Li, Song Gong, Qi Zhang","doi":"10.1016/j.tips.2024.09.007","DOIUrl":"10.1016/j.tips.2024.09.007","url":null,"abstract":"<p><p>Wound healing is a complex and orchestrated process that involves hemostasis, inflammation, proliferation, and tissue remodeling. Neutrophil extracellular traps (NETs) are intricate web-like structures released by neutrophils, comprising decondensed chromatin, myeloperoxidase (MPO), and neutrophil elastase (NE), which play vital roles in regulating neutrophil-mediated immune regulation. While NETs contribute to wound healing, excessive activation induced by dysregulated inflammation can hinder the healing process. Understanding the pivotal role of NETs in wound healing and tissue remodeling, as well as their intricate interactions within the wound microenvironment, presents opportunities for innovative wound healing strategies. In this review we discuss the process of NET formation, explore the interactions between NETs and skin cells, and examine therapeutic strategies targeting NETs and drug delivery platforms to accelerate wound healing. Additionally, we discuss current clinical investigations and research challenges towards advancing wound care practices.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1033-1045"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475601","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}
引用次数: 0
Enhancing CNS mitophagy: drug development and disease-relevant models. 增强中枢神经系统有丝分裂：药物开发和疾病相关模型。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI: 10.1016/j.tips.2024.09.002
Krishayant S Dhar, Brendan Townsend, Andrew P Montgomery, Jonathan J Danon, Julia K Pagan, Michael Kassiou
{"title":"Enhancing CNS mitophagy: drug development and disease-relevant models.","authors":"Krishayant S Dhar, Brendan Townsend, Andrew P Montgomery, Jonathan J Danon, Julia K Pagan, Michael Kassiou","doi":"10.1016/j.tips.2024.09.002","DOIUrl":"10.1016/j.tips.2024.09.002","url":null,"abstract":"<p><p>Mitophagy, the selective degradation of mitochondria, is impaired in many neurodegenerative diseases (NDs), resulting in an accumulation of dysfunctional mitochondria and neuronal damage. Although enhancing mitophagy shows promise as a therapeutic strategy, the clinical significance of mitophagy activators remains uncertain due to limited understanding and poor representation of mitophagy in the central nervous system (CNS). This review explores recent insights into which mitophagy pathways to target and the extent of modulation necessary to be therapeutic towards NDs. We also highlight the complexities of mitophagy in the CNS, highlighting the need for disease-relevant models. Last, we outline crucial aspects of in vitro models to consider during drug discovery, aiming to bridge the gap between preclinical research and clinical applications in treating NDs through mitophagy modulation.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"982-996"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475599","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}
引用次数: 0
Integrated computational approaches for advancing antimicrobial peptide development. 推进抗菌肽开发的综合计算方法。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-25 DOI: 10.1016/j.tips.2024.09.011
Yanpeng Fang, Yeshuo Ma, Kunqian Yu, Jie Dong, Wenbin Zeng
{"title":"Integrated computational approaches for advancing antimicrobial peptide development.","authors":"Yanpeng Fang, Yeshuo Ma, Kunqian Yu, Jie Dong, Wenbin Zeng","doi":"10.1016/j.tips.2024.09.011","DOIUrl":"10.1016/j.tips.2024.09.011","url":null,"abstract":"<p><p>The increasing prevalence of antimicrobial resistance has intensified the need for novel antimicrobial drugs. Antimicrobial peptides (AMPs) are promising alternative antibiotics due to their broad-spectrum activity and slower resistance development. However, the time-consuming, costly development and challenge of systematic optimization limit their translation into the clinic. Recently, integrating computational methods have led to breakthroughs in the precise design and optimization of AMPs, reduced resource consumption, and accelerated AMP development process. We highlight the application of these integrated approaches in AMP molecule discovery, optimization, and delivery and demonstrate the synergy of these strategies to fuel AMP development.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1046-1060"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569156","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}
引用次数: 0
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