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Annual review of pharmacology and toxicology最新文献

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Progress and Challenges in the Field of Snakebite Envenoming Therapeutics. 蛇咬致病疗法领域的进展与挑战。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-08-01 DOI: 10.1146/annurev-pharmtox-022024-033544
José María Gutiérrez, Nicholas R Casewell, Andreas H Laustsen
{"title":"Progress and Challenges in the Field of Snakebite Envenoming Therapeutics.","authors":"José María Gutiérrez, Nicholas R Casewell, Andreas H Laustsen","doi":"10.1146/annurev-pharmtox-022024-033544","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-022024-033544","url":null,"abstract":"<p><p>Snakebite envenoming kills and maims hundreds of thousands of people every year, especially in the rural settings of tropical regions. Envenomings are still treated with animal-derived antivenoms, which have prevented many lives from being lost but which are also medicines in need of innovation. Strides are being made to improve envenoming therapies, with promising efforts made toward optimizing manufacturing and quality aspects of existing antivenoms, accelerating research and development of recombinant antivenoms based on monoclonal antibodies, and repurposing of small-molecule inhibitors that block key toxins. Here, we review the most recent advances in these fields and discuss therapeutic opportunities and limitations for different snakebite treatment modalities. Finally, we discuss challenges related to preclinical and clinical evaluation, regulatory pathways, large-scale manufacture, and distribution and access that need to be addressed to fulfill the goals of the World Health Organization's global strategy to prevent and control snakebite envenoming.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":11.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873984","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
Prospects for Disease Slowing in Parkinson Disease. 帕金森病的疾病减缓前景。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-08-01 DOI: 10.1146/annurev-pharmtox-022124-033653
Elisa Menozzi, Anthony H V Schapira
{"title":"Prospects for Disease Slowing in Parkinson Disease.","authors":"Elisa Menozzi, Anthony H V Schapira","doi":"10.1146/annurev-pharmtox-022124-033653","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-022124-033653","url":null,"abstract":"<p><p>The increasing prevalence of Parkinson disease (PD) highlights the need to develop interventions aimed at slowing or halting its progression. As a result of sophisticated disease modeling in preclinical studies, and refinement of specific clinical/genetic/pathological profiles, our understanding of PD pathogenesis has grown over the years, leading to the identification of several targets for disease modification. This has translated to the development of targeted therapies, many of which have entered clinical trials. Nonetheless, up until now, none of these treatments have satisfactorily shown disease-modifying effects in PD. In this review, we present the most up-to-date disease-modifying pharmacological interventions in the clinical trial pipeline for PD. We focus on agents that have reached more advanced stages of clinical trials testing, highlighting both positive and negative results, and critically reflect on strengths, weaknesses, and challenges of current disease-modifying therapeutic avenues in PD.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":11.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873985","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
Diffuse Pleural Mesothelioma: Advances in Molecular Pathogenesis, Diagnosis, and Treatment. 弥漫性胸膜间皮瘤：分子发病机制、诊断和治疗进展。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-24 Epub Date: 2023-09-18 DOI: 10.1146/annurev-pathol-042420-092719
Christopher A Febres-Aldana, Rachel Fanaroff, Michael Offin, Marjorie G Zauderer, Jennifer L Sauter, Soo-Ryum Yang, Marc Ladanyi
{"title":"Diffuse Pleural Mesothelioma: Advances in Molecular Pathogenesis, Diagnosis, and Treatment.","authors":"Christopher A Febres-Aldana, Rachel Fanaroff, Michael Offin, Marjorie G Zauderer, Jennifer L Sauter, Soo-Ryum Yang, Marc Ladanyi","doi":"10.1146/annurev-pathol-042420-092719","DOIUrl":"10.1146/annurev-pathol-042420-092719","url":null,"abstract":"<p><p>Diffuse pleural mesothelioma (DPM) is a highly aggressive malignant neoplasm arising from the mesothelial cells lining the pleural surfaces. While DPM is a well-recognized disease linked to asbestos exposure, recent advances have expanded our understanding of molecular pathogenesis and transformed our clinical practice. This comprehensive review explores the current concepts and emerging trends in DPM, including risk factors, pathobiology, histologic subtyping, and therapeutic management, with an emphasis on a multidisciplinary approach to this complex disease.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10673542","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
Dynamic Multiplex Tissue Imaging in Inflammation Research. 炎症研究中的动态多重组织成像。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-24 Epub Date: 2023-09-18 DOI: 10.1146/annurev-pathmechdis-070323-124158
Stefan Uderhardt, Georgiana Neag, Ronald N Germain
{"title":"Dynamic Multiplex Tissue Imaging in Inflammation Research.","authors":"Stefan Uderhardt, Georgiana Neag, Ronald N Germain","doi":"10.1146/annurev-pathmechdis-070323-124158","DOIUrl":"10.1146/annurev-pathmechdis-070323-124158","url":null,"abstract":"<p><p>Inflammation is a highly dynamic process with immune cells that continuously interact with each other and parenchymal components as they migrate through tissue. The dynamic cellular responses and interaction patterns are a function of the complex tissue environment that cannot be fully reconstructed ex vivo, making it necessary to assess cell dynamics and changing spatial patterning in vivo. These dynamics often play out deep within tissues, requiring the optical focus to be placed far below the surface of an opaque organ. With the emergence of commercially available two-photon excitation lasers that can be combined with existing imaging systems, new avenues for imaging deep tissues over long periods of time have become available. We discuss a selected subset of studies illustrating how two-photon microscopy (2PM) has helped to relate the dynamics of immune cells to their in situ function and to understand the molecular patterns that govern their behavior in vivo. We also review some key practical aspects of 2PM methods and point out issues that can confound the results, so that readers can better evaluate the reliability of conclusions drawn using this technology.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10673543","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
The Nocebo Effect. 恐慌效应
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-08-16 DOI: 10.1146/annurev-pharmtox-022723-112425
Luana Colloca
{"title":"The Nocebo Effect.","authors":"Luana Colloca","doi":"10.1146/annurev-pharmtox-022723-112425","DOIUrl":"10.1146/annurev-pharmtox-022723-112425","url":null,"abstract":"<p><p>Adverse nocebo responses can cause harm to patients and interfere with treatment adherence and effects in both clinic practice and clinical trials. Nocebo responses refer to negative outcomes to active medical treatments in clinical trials or practice that cannot be explained by the treatment's pharmacologic effects. Negative expectancies and nocebo effects are less known than placebo responses. Nocebo effects can be triggered by verbal suggestions, prior negative experiences, observation of others experiencing negative outcomes, and other contextual and environmental factors. As research advances over the years, mechanistic knowledge is accumulating on the neurobiological mechanisms of nocebo effects. This review summarizes studies on different facets of nocebo effects and responses and discusses clinical implications, ethical considerations, and future directions.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10868531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004521","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
Circulating Biomarkers Instead of Genotyping to Establish Metabolizer Phenotypes. 用循环生物标记物代替基因分型来确定代谢物表型。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-08-16 DOI: 10.1146/annurev-pharmtox-032023-121106
Roman Tremmel, Ute Hofmann, Mathias Haag, Elke Schaeffeler, Matthias Schwab
{"title":"Circulating Biomarkers Instead of Genotyping to Establish Metabolizer Phenotypes.","authors":"Roman Tremmel, Ute Hofmann, Mathias Haag, Elke Schaeffeler, Matthias Schwab","doi":"10.1146/annurev-pharmtox-032023-121106","DOIUrl":"10.1146/annurev-pharmtox-032023-121106","url":null,"abstract":"<p><p>Pharmacogenomics (PGx) enables personalized treatment for the prediction of drug response and to avoid adverse drug reactions. Currently, PGx mainly relies on the genetic information of absorption, distribution, metabolism, and excretion (ADME) targets such as drug-metabolizing enzymes or transporters to predict differences in the patient's phenotype. However, there is evidence that the phenotype-genotype concordance is limited. Thus, we discuss different phenotyping strategies using exogenous xenobiotics (e.g., drug cocktails) or endogenous compounds for phenotype prediction. In particular, minimally invasive approaches focusing on liquid biopsies offer great potential to preemptively determine metabolic and transport capacities. Early studies indicate that ADME phenotyping using exosomes released from the liver is reliable. In addition, pharmacometric modeling and artificial intelligence improve phenotype prediction. However, further prospective studies are needed to demonstrate the clinical utility of individualized treatment based on phenotyping strategies, not only relying on genetics. The present review summarizes current knowledge and limitations.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10013253","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
Mass Spectrometry-Based Proteogenomics: New Therapeutic Opportunities for Precision Medicine. 基于质谱的蛋白质组学：精准医学的新治疗机会。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-09-22 DOI: 10.1146/annurev-pharmtox-022723-113921
Sunil K Joshi, Paul Piehowski, Tao Liu, Sara J C Gosline, Jason E McDermott, Brian J Druker, Elie Traer, Jeffrey W Tyner, Anupriya Agarwal, Cristina E Tognon, Karin D Rodland
{"title":"Mass Spectrometry-Based Proteogenomics: New Therapeutic Opportunities for Precision Medicine.","authors":"Sunil K Joshi, Paul Piehowski, Tao Liu, Sara J C Gosline, Jason E McDermott, Brian J Druker, Elie Traer, Jeffrey W Tyner, Anupriya Agarwal, Cristina E Tognon, Karin D Rodland","doi":"10.1146/annurev-pharmtox-022723-113921","DOIUrl":"10.1146/annurev-pharmtox-022723-113921","url":null,"abstract":"<p><p>Proteogenomics refers to the integration of comprehensive genomic, transcriptomic, and proteomic measurements from the same samples with the goal of fully understanding the regulatory processes converting genotypes to phenotypes, often with an emphasis on gaining a deeper understanding of disease processes. Although specific genetic mutations have long been known to drive the development of multiple cancers, gene mutations alone do not always predict prognosis or response to targeted therapy. The benefit of proteogenomics research is that information obtained from proteins and their corresponding pathways provides insight into therapeutic targets that can complement genomic information by providing an additional dimension regarding the underlying mechanisms and pathophysiology of tumors. This review describes the novel insights into tumor biology and drug resistance derived from proteogenomic analysis while highlighting the clinical potential of proteogenomic observations and advances in technique and analysis tools.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41094754","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
Apathy and Motivation: Biological Basis and Drug Treatment. 冷漠与动机：生物基础与药物治疗
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-08-16 DOI: 10.1146/annurev-pharmtox-022423-014645
Harry Costello, Masud Husain, Jonathan P Roiser
{"title":"Apathy and Motivation: Biological Basis and Drug Treatment.","authors":"Harry Costello, Masud Husain, Jonathan P Roiser","doi":"10.1146/annurev-pharmtox-022423-014645","DOIUrl":"10.1146/annurev-pharmtox-022423-014645","url":null,"abstract":"<p><p>Apathy is a disabling syndrome associated with poor functional outcomes that is common across a broad range of neurological and psychiatric conditions. Currently, there are no established therapies specifically for the condition, and safe and effective treatments are urgently needed. Advances in the understanding of motivation and goal-directed behavior in humans and animals have shed light on the cognitive and neurobiological mechanisms contributing to apathy, providing an important foundation for the development of new treatments. Here, we review the cognitive components, neural circuitry, and pharmacology of apathy and motivation, highlighting converging evidence of shared transdiagnostic mechanisms. Though no pharmacological treatments have yet been licensed, we summarize trials of existing and novel compounds to date, identifying several promising candidates for clinical use and avenues of future drug development.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004518","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
From Thalidomide to Rational Molecular Glue Design for Targeted Protein Degradation. 从沙利度胺到靶向蛋白质降解的合理分子胶设计
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-08-16 DOI: 10.1146/annurev-pharmtox-022123-104147
Vladas Oleinikovas, Pablo Gainza, Thomas Ryckmans, Bernhard Fasching, Nicolas H Thomä
{"title":"From Thalidomide to Rational Molecular Glue Design for Targeted Protein Degradation.","authors":"Vladas Oleinikovas, Pablo Gainza, Thomas Ryckmans, Bernhard Fasching, Nicolas H Thomä","doi":"10.1146/annurev-pharmtox-022123-104147","DOIUrl":"10.1146/annurev-pharmtox-022123-104147","url":null,"abstract":"<p><p>Thalidomide and its derivatives are powerful cancer therapeutics that are among the best-understood molecular glue degraders (MGDs). These drugs selectively reprogram the E3 ubiquitin ligase cereblon (CRBN) to commit target proteins for degradation by the ubiquitin-proteasome system. MGDs create novel recognition interfaces on the surface of the E3 ligase that engage in induced protein-protein interactions with neosubstrates. Molecular insight into their mechanism of action opens exciting opportunities to engage a plethora of targets through a specific recognition motif, the G-loop. Our analysis shows that current CRBN-based MGDs can in principle recognize over 2,500 proteins in the human proteome that contain a G-loop. We review recent advances in tuning the specificity between CRBN and its MGD-induced neosubstrates and deduce a set of simple rules that govern these interactions. We conclude that rational MGD design efforts will enable selective degradation of many more proteins, expanding this therapeutic modality to more disease areas.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10013249","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
Circadian Regulation of Drug Responses: Toward Sex-Specific and Personalized Chronotherapy. 药物反应的昼夜节律调节：实现性别特异性和个性化的慢性疗法
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-09-18 DOI: 10.1146/annurev-pharmtox-051920-095416
Francis A Lévi, Alper Okyar, Eva Hadadi, Pasquale F Innominato, Annabelle Ballesta
{"title":"Circadian Regulation of Drug Responses: Toward Sex-Specific and Personalized Chronotherapy.","authors":"Francis A Lévi, Alper Okyar, Eva Hadadi, Pasquale F Innominato, Annabelle Ballesta","doi":"10.1146/annurev-pharmtox-051920-095416","DOIUrl":"10.1146/annurev-pharmtox-051920-095416","url":null,"abstract":"<p><p>Today's challenge for precision medicine involves the integration of the impact of molecular clocks on drug pharmacokinetics, toxicity, and efficacy toward personalized chronotherapy. Meaningful improvements of tolerability and/or efficacy of medications through proper administration timing have been confirmed over the past decade for immunotherapy and chemotherapy against cancer, as well as for commonly used pharmacological agents in cardiovascular, metabolic, inflammatory, and neurological conditions. Experimental and human studies have recently revealed sexually dimorphic circadian drug responses. Dedicated randomized clinical trials should now aim to issue personalized circadian timing recommendations for daily medical practice, integrating innovative technologies for remote longitudinal monitoring of circadian metrics, statistical prediction of molecular clock function from single-timepoint biopsies, and multiscale biorhythmic mathematical modelling. Importantly, chronofit patients with a robust circadian function, who would benefit most from personalized chronotherapy, need to be identified. Conversely, nonchronofit patients could benefit from the emerging pharmacological class of chronobiotics targeting the circadian clock.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10311547","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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