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Annual review of pharmacology and toxicology最新文献

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Trichloroethylene: An Update on an Environmental Contaminant with Multiple Health Effects. 三氯乙烯：一种对健康有多重影响的环境污染物的最新情况。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1146/annurev-pharmtox-022724-120525
Lawrence H Lash
{"title":"Trichloroethylene: An Update on an Environmental Contaminant with Multiple Health Effects.","authors":"Lawrence H Lash","doi":"10.1146/annurev-pharmtox-022724-120525","DOIUrl":"10.1146/annurev-pharmtox-022724-120525","url":null,"abstract":"<p><p>The halogenated solvent trichloroethylene (TCE) has had many uses in medicine, construction, consumer products, and the military. Many of these uses have been discontinued or restricted due to its toxicity, which affects multiple target organs and includes both acute, high-dose toxicity and chronic, low-dose toxicity that also encompass several cancers. US and international agencies have conducted risk and hazard assessments for TCE, with comprehensive publications coming out in the last 10-15 years. Accordingly, the focus of this article is to review recently published data since that time (i.e., 2014) that clarify unsettled questions or provide additional insights into the metabolism and mechanisms of toxicity of TCE in several target organs. Besides metabolism, the review focuses on the kidneys, liver, immune system, nervous system, cardiovascular and pulmonary systems, the search for biomarkers, and recent analyses of human cancer risk and incidence from TCE exposure.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"507-527"},"PeriodicalIF":11.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878248","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
Pharmacogenetics: Opportunities for the All of Us Research Program and Other Large Data Sets to Advance the Field. 药物遗传学：我们所有人的研究计划和其他大型数据集推进该领域的机会。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-01-01 DOI: 10.1146/annurev-pharmtox-061724-080718
Philip E Empey, Jason H Karnes, Julie A Johnson
{"title":"Pharmacogenetics: Opportunities for the <i>All of Us</i> Research Program and Other Large Data Sets to Advance the Field.","authors":"Philip E Empey, Jason H Karnes, Julie A Johnson","doi":"10.1146/annurev-pharmtox-061724-080718","DOIUrl":"10.1146/annurev-pharmtox-061724-080718","url":null,"abstract":"<p><p>Pharmacogenetic variation is common and an established driver of response for many drugs. There has been tremendous progress in pharmacogenetics knowledge over the last 30 years and in clinical implementation of that knowledge over the last 15 years. But there have also been many examples where translation has stalled because of the lack of available data sets for discovery or validation research. The recent availability of data from very large cohorts with linked genetic, electronic health record, and other data promises new opportunities to advance pharmacogenetics research. This review presents the stages from pharmacogenetics discovery to widespread clinical adoption using prominent gene-drug pairs that have been implemented into clinical practice as examples. We discuss the opportunities that the <i>All of Us</i> Research Program and other large biorepositories with genomic and linked electronic health record data present in advancing and accelerating the translation of pharmacogenetics into clinical practice.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"65 1","pages":"111-130"},"PeriodicalIF":11.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027673","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
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 : 2025-01-01 Epub Date: 2024-12-17 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":"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":" ","pages":"237-258"},"PeriodicalIF":11.2,"publicationDate":"2025-01-01","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
Opportunities for Microphysiological Systems in Toxicity Testing of New Drug Modalities. 微观生理学系统在新药毒性测试中的机遇。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1146/annurev-pharmtox-061724-080621
Tengku Ibrahim Maulana, Nienke R Wevers, Theodora Kristoforus, Morgan Chandler, Henriette L Lanz, Jos Joore, Paul Vulto, Remi Villenave, Stefan Kustermann, Peter Loskill, Kristin M Bircsak
{"title":"Opportunities for Microphysiological Systems in Toxicity Testing of New Drug Modalities.","authors":"Tengku Ibrahim Maulana, Nienke R Wevers, Theodora Kristoforus, Morgan Chandler, Henriette L Lanz, Jos Joore, Paul Vulto, Remi Villenave, Stefan Kustermann, Peter Loskill, Kristin M Bircsak","doi":"10.1146/annurev-pharmtox-061724-080621","DOIUrl":"10.1146/annurev-pharmtox-061724-080621","url":null,"abstract":"<p><p>New drug modalities offer life-saving benefits for patients through access to previously undruggable targets. Yet these modalities pose a challenge for the pharmaceutical industry, as side effects are complex, unpredictable, and often uniquely human. With animal studies having limited predictive value due to translatability challenges, the pharmaceutical industry seeks out new approach methodologies. Microphysiological systems (MPS) offer important features that enable complex toxicological processes to be modeled in vitro such as (<i>a</i>) an adjustable complexity of cellular components, including immune components; (<i>b</i>) a modifiable tissue architecture; (<i>c</i>) integration and monitoring of dynamic mechanisms; and (<i>d</i>) a multiorgan connection. Here we review MPS studies in the context of four clinical adverse events triggered by new drug modalities: peripheral neuropathy, thrombocytopenia, immune-mediated hepatotoxicity, and cytokine release syndrome. We conclude that while the use of MPS for testing new drug modality-induced toxicities is still in its infancy, we see strong potential going forward.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"47-69"},"PeriodicalIF":11.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124645","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
Pharmacology of Intestinal Inflammation and Repair. 肠道炎症与修复的药理学。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-01-01 DOI: 10.1146/annurev-pharmtox-051921-084536
Céline Deraison, Nathalie Vergnolle
{"title":"Pharmacology of Intestinal Inflammation and Repair.","authors":"Céline Deraison, Nathalie Vergnolle","doi":"10.1146/annurev-pharmtox-051921-084536","DOIUrl":"10.1146/annurev-pharmtox-051921-084536","url":null,"abstract":"<p><p>Chronic inflammation is a common trait in the pathogenesis of several diseases of the gut, including inflammatory bowel disease and celiac disease. Control of the inflammatory response is crucial in these pathologies to avoid tissue destruction and loss of intestinal function. Over the last 50 years, the identification of the mechanisms and mediators involved in the acute phase of the inflammatory response, which is characterized by massive leukocyte recruitment, has led to a number of therapeutic options. New drugs targeting inflammatory flares are still under development. However, interest on the other end of the spectrum-the resolution and repair phases-has emerged, as promoting tissue functional repair may maintain remission and counteract the chronicity of the disease. This review aims to discuss the current and future pharmacological approaches to the treatment of chronic intestinal inflammation and the restoration of functional tissues.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"65 1","pages":"301-314"},"PeriodicalIF":11.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027690","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
Introduction to the Theme "Novel Therapeutics with the Potential to Advance Health Care". 主题 "有可能促进医疗保健的新型疗法 "介绍。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1146/annurev-pharmtox-090324-021727
Paul A Insel, Susan G Amara, Amrita Ahluwalia
{"title":"Introduction to the Theme \"Novel Therapeutics with the Potential to Advance Health Care\".","authors":"Paul A Insel, Susan G Amara, Amrita Ahluwalia","doi":"10.1146/annurev-pharmtox-090324-021727","DOIUrl":"10.1146/annurev-pharmtox-090324-021727","url":null,"abstract":"<p><p>The reviews in Volume 65 of the <i>Annual Review of Pharmacology and Toxicology</i> cover a wide variety of topics in pharmacology and toxicology focused upon the pathway from preclinical studies to clinical trials. Many of these reviews discuss the identification and validation of new therapeutic targets and/or novel therapeutic approaches. Examples include reviews that focus on the treatment of obesity, neuropsychiatric disorders, Parkinson's disease, substance use disorders, liver fibrosis, cardiac arrythmias, chronic intestinal inflammation, prostate cancer, immuno-oncology, sickle cell disease, and snakebite envenoming. Other topics include drug discovery of biologics, microphysiological systems, and human induced pluripotent stem cell-derived organoids and organ-on-chip technology integrated with artificial intelligence methodologies. Together, these and other reviews give new insights into the assessment of aspects of toxicology and provide readers a glimpse of advances in pharmacology and toxicology that we believe will advance health care and environmental safety.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"1-5"},"PeriodicalIF":11.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339827","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
How Biologics Have Changed the Drug Discovery Landscape. 生物制剂如何改变了药物研发格局。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1146/annurev-pharmtox-061724-080811
Paul McGonigle
{"title":"How Biologics Have Changed the Drug Discovery Landscape.","authors":"Paul McGonigle","doi":"10.1146/annurev-pharmtox-061724-080811","DOIUrl":"10.1146/annurev-pharmtox-061724-080811","url":null,"abstract":"<p><p>Advances in molecular biology and molecular genetics as well as major scientific breakthroughs in immunology and oncology have led to the rapid growth of biologic therapeutics. Their success has resulted in significant changes to virtually every step in the drug discovery and development process. Biologics are produced by living organisms, and screening libraries are generated by immunization or phage display. Lead optimization utilizes sophisticated protein engineering to improve drug-like properties and targeting specificity. The manufacturing process for biologics is complex and requires highly specialized facilities. Determination of pharmacology and safety must overcome the complications associated with species specificity. Initial clinical testing must proceed more slowly and carefully due to the limited predictive utility of preclinical data. In summary, the drug discovery and development process has been dramatically altered by biologic therapeutics and will continue to evolve with the introduction of messenger RNA-based therapeutics and the application of artificial intelligence.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"29-46"},"PeriodicalIF":11.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399198","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
Next-Gen Therapeutics: Pioneering Drug Discovery with iPSCs, Genomics, AI, and Clinical Trials in a Dish. 新一代疗法：用 iPSC、基因组学、人工智能和临床试验在一个碟子里进行药物发现的先驱。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1146/annurev-pharmtox-022724-095035
Zehra Yildirim, Kyle Swanson, Xuekun Wu, James Zou, Joseph Wu
{"title":"Next-Gen Therapeutics: Pioneering Drug Discovery with iPSCs, Genomics, AI, and Clinical Trials in a Dish.","authors":"Zehra Yildirim, Kyle Swanson, Xuekun Wu, James Zou, Joseph Wu","doi":"10.1146/annurev-pharmtox-022724-095035","DOIUrl":"10.1146/annurev-pharmtox-022724-095035","url":null,"abstract":"<p><p>In the high-stakes arena of drug discovery, the journey from bench to bedside is hindered by a daunting 92% failure rate, primarily due to unpredicted toxicities and inadequate therapeutic efficacy in clinical trials. The FDA Modernization Act 2.0 heralds a transformative approach, advocating for the integration of alternative methods to conventional animal testing, including cell-based assays that employ human induced pluripotent stem cell (iPSC)-derived organoids, and organ-on-a-chip technologies, in conjunction with sophisticated artificial intelligence (AI) methodologies. Our review explores the innovative capacity of iPSC-derived clinical trial in a dish models designed for cardiovascular disease research. We also highlight how integrating iPSC technology with AI can accelerate the identification of viable therapeutic candidates, streamline drug screening, and pave the way toward more personalized medicine. Through this, we provide a comprehensive overview of the current landscape and future implications of iPSC and AI applications being navigated by the research community and pharmaceutical industry.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"71-90"},"PeriodicalIF":11.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279686","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
Targeting G Protein–Coupled Receptors in Immuno-Oncological Therapies 以免疫肿瘤疗法中的 G 蛋白偶联受体为靶点
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-09-13 DOI: 10.1146/annurev-pharmtox-061724-080852
John Stagg, J. Silvio Gutkind
{"title":"Targeting G Protein–Coupled Receptors in Immuno-Oncological Therapies","authors":"John Stagg, J. Silvio Gutkind","doi":"10.1146/annurev-pharmtox-061724-080852","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-061724-080852","url":null,"abstract":"The advent of cancer immunotherapy based on PD-1 and CTLA-4 immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, many cancers do not respond to ICB, highlighting the urgent need for additional approaches to achieve durable cancer remission. The large family of G protein–coupled receptors (GPCRs) is the target of more than 30% of all approved drugs, but GPCRs have been underexploited in cancer immunotherapy. In this review, we discuss the central role of GPCRs in immune cell migration and function and describe how single-cell transcriptomic studies are illuminating the complexity of the human tumor immune GPCRome. These receptors include multiple GPCRs expressed in CD8 T cells that are activated by inflammatory mediators, protons, neurotransmitters, and metabolites that accumulate in the tumor microenvironment, thereby promoting T cell dysfunction. We also discuss new opportunities to target GPCRs as a multimodal approach to enhance the response to ICB for a myriad of human malignancies.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"32 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265234","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
Advancements in Assays for Micro- and Nanoplastic Detection: Paving the Way for Biomonitoring and Exposomics Studies 微塑料和纳米塑料检测试验的进展：为生物监测和暴露组学研究铺平道路
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-09-13 DOI: 10.1146/annurev-pharmtox-030424-112828
Kuanliang Shao, Runyu Zou, Zhuoyue Zhang, Laurens D.B. Mandemaker, Sarah Timbie, Ronald D. Smith, Amanda M. Durkin, Hanna M. Dusza, Florian Meirer, Bert M. Weckhuysen, Tanya L. Alderete, Roel Vermuelen, Douglas I. Walker
{"title":"Advancements in Assays for Micro- and Nanoplastic Detection: Paving the Way for Biomonitoring and Exposomics Studies","authors":"Kuanliang Shao, Runyu Zou, Zhuoyue Zhang, Laurens D.B. Mandemaker, Sarah Timbie, Ronald D. Smith, Amanda M. Durkin, Hanna M. Dusza, Florian Meirer, Bert M. Weckhuysen, Tanya L. Alderete, Roel Vermuelen, Douglas I. Walker","doi":"10.1146/annurev-pharmtox-030424-112828","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-030424-112828","url":null,"abstract":"Although plastic pollution and exposure to plastic-related compounds have received worldwide attention, health risks associated with micro- and nanoplastics (MNPs) are largely unknown. Emerging evidence suggests MNPs are present in human biofluids and tissue, including blood, breast milk, stool, lung tissue, and placenta; however, exposure assessment is limited and the extent of human exposure to MNPs is not well known. While there is a critical need to establish robust and scalable biomonitoring strategies to assess human exposure to MNPs and plastic-related chemicals, over 10,000 chemicals have been linked to plastic manufacturing with no existing standardized approaches to account for even a fraction of these exposures. This review provides an overview of the status of methods for measuring MNPs and associated plastic-related chemicals in humans, with a focus on approaches that could be adapted for population-wide biomonitoring and integration with biological response measures to develop hypotheses on potential health effects of plastic exposures. We also examine the exposure risks associated with the widespread use of chemical additives in plastics. Despite advancements in analytical techniques, there remains a pressing need for standardized measurement protocols and untargeted, high-throughput analysis methods to enable comprehensive MNP biomonitoring to identify key MNP exposures in human populations. This review aims to merge insights into the toxicological effects of MNPs and plastic additives with an evaluation of analytical challenges, advocating for enhanced research methods to fully assess, understand, and mitigate the public health implications of MNPs.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"6 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265233","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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