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Annual review of pharmacology and toxicology最新文献

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Immunoregulation of Liver Fibrosis: New Opportunities for Antifibrotic Therapy 肝纤维化的免疫调节：抗纤维化疗法的新机遇
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-09-11 DOI: 10.1146/annurev-pharmtox-020524-012013
Helene Gilgenkrantz, Rola Al Sayegh, Sophie Lotersztajn
{"title":"Immunoregulation of Liver Fibrosis: New Opportunities for Antifibrotic Therapy","authors":"Helene Gilgenkrantz, Rola Al Sayegh, Sophie Lotersztajn","doi":"10.1146/annurev-pharmtox-020524-012013","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-020524-012013","url":null,"abstract":"Liver fibrosis develops in response to chronic liver injury and is characterized by a sustained inflammatory response that leads to excessive collagen deposition by myofibroblasts. The fibrogenic response is governed by the release of inflammatory mediators from innate, adaptive, and innate-like lymphoid cells and from nonprofessional immune cells (i.e., epithelial cells, hepatic myofibroblasts, and liver sinusoidal endothelial cells). Upon removal of the underlying cause, liver fibrosis can resolve via activation of specific immune cell subsets. Despite major advances in the understanding of fibrosis pathogenesis, there is still no approved antifibrotic therapy. This review summarizes our current knowledge of the immune cell landscape and the inflammatory mechanisms underlying liver fibrosis progression and regression. We discuss how reprogramming immune cell phenotype, in particular through targeting selective inflammatory pathways or modulating cell-intrinsic metabolism, may be translated into antifibrogenic therapies.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225518","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
Gut Microbiota–Related Biomarkers in Immuno-Oncology 免疫肿瘤学中与肠道微生物群相关的生物标记物
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-09-11 DOI: 10.1146/annurev-pharmtox-061124-102218
Carolina Alves Costa Silva, Marine Fidelle, Andrew A. Almonte, Lisa Derosa, Laurence Zitvogel
{"title":"Gut Microbiota–Related Biomarkers in Immuno-Oncology","authors":"Carolina Alves Costa Silva, Marine Fidelle, Andrew A. Almonte, Lisa Derosa, Laurence Zitvogel","doi":"10.1146/annurev-pharmtox-061124-102218","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-061124-102218","url":null,"abstract":"Carcinogenesis is associated with the emergence of protracted intestinal dysbiosis and metabolic changes. Increasing evidence shows that gut microbiota–related biomarkers and microbiota-centered interventions are promising strategies to overcome resistance to immunotherapy. However, current standard methods for evaluating gut microbiota composition are cost- and time-consuming. The development of routine diagnostic tools for intestinal barrier alterations and dysbiosis constitutes a critical unmet medical need that can guide routine treatment and microbiota-centered intervention decisions in patients with cancer. In this review, we explore the influence of gut microbiota on cancer immunotherapy and highlight gut-associated biomarkers that have the potential to be transformed into simple diagnostic tools, thus guiding standard treatment decisions in the field of immuno-oncology. Mechanistic insights toward leveraging the complex relationship between cancer immunosurveillance, gut microbiota, and metabolism open exciting opportunities for developing novel biomarkers in immuno-oncology.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225517","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
Treating Sickle Cell Disease: Gene Therapy Approaches 治疗镰状细胞病：基因治疗方法
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-09-11 DOI: 10.1146/annurev-pharmtox-022124-022000
Marina Cavazzana, Alice Corsia, Megane Brusson, Annarita Miccio, Michaela Semeraro
{"title":"Treating Sickle Cell Disease: Gene Therapy Approaches","authors":"Marina Cavazzana, Alice Corsia, Megane Brusson, Annarita Miccio, Michaela Semeraro","doi":"10.1146/annurev-pharmtox-022124-022000","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-022124-022000","url":null,"abstract":"Sickle cell disease (SCD) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin molecules and thus distortion (sickling) of the red blood cells. SCD causes chronic pain and organ damage and shortens life expectancy. Gene therapy emerges as a potentially curative approach for people with SCD who lack a matched sibling donor for hematopoietic stem cell transplantation. Here, we review recent progress in gene therapy for SCD and focus on innovative technologies that target the genetic roots of the disease. We also review the challenges associated with gene therapy, including oncogenic risks, and the need for refined delivery methods. Despite these hurdles, the rapidly evolving landscape of gene therapy for SCD raises hope for a paradigm shift in the treatment of this debilitating disease. As research progresses, a deeper understanding of the molecular mechanisms involved and continuous improvements in gene-editing technologies promise to bring gene therapy for SCD closer to mainstream clinical application, offering a transformative, curative option for patients with this genetic disorder.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142199106","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
Weight Loss Blockbuster Development: A Role for Unimolecular Polypharmacology 减肥大片的开发：单分子多药理学的作用
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-09-11 DOI: 10.1146/annurev-pharmtox-061324-011832
Qingtong Zhou, Guanyi Li, Kaini Hang, Jie Li, Dehua Yang, Ming-Wei Wang
{"title":"Weight Loss Blockbuster Development: A Role for Unimolecular Polypharmacology","authors":"Qingtong Zhou, Guanyi Li, Kaini Hang, Jie Li, Dehua Yang, Ming-Wei Wang","doi":"10.1146/annurev-pharmtox-061324-011832","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-061324-011832","url":null,"abstract":"Obesity and type 2 diabetes mellitus (T2DM) impact more than 2.5 billion adults worldwide, necessitating innovative therapeutic approaches. Unimolecular polypharmacology, which involves designing single molecules to target multiple receptors or pathways simultaneously, has revolutionized treatment strategies. Blockbuster drugs such as tirzepatide and retatrutide have shown unprecedented success in managing obesity and T2DM, demonstrating superior efficacy compared to conventional single agonists. Tirzepatide, in particular, has garnered tremendous attention for its remarkable effectiveness in promoting weight loss and improving glycemic control, while offering additional cardiovascular and renal benefits. Despite their promises, such therapeutic agents also face challenges that include gastrointestinal side effects, patient compliance issues, and body weight rebound after cessation of the treatment. Nonetheless, the development of these therapies marks a significant leap forward, underscoring the transformative potential of unimolecular polypharmacology in addressing metabolic diseases and paving the way for future innovations in personalized medicine.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225516","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
Pollution of Soil by Pharmaceuticals: Implications for Metazoan and Environmental Health. 药物对土壤的污染：对元虫和环境健康的影响。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-09-03 DOI: 10.1146/annurev-pharmtox-030124-111214
Chubin Zhang, Leon P Barron, Stephen R Stürzenbaum
{"title":"Pollution of Soil by Pharmaceuticals: Implications for Metazoan and Environmental Health.","authors":"Chubin Zhang, Leon P Barron, Stephen R Stürzenbaum","doi":"10.1146/annurev-pharmtox-030124-111214","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-030124-111214","url":null,"abstract":"<p><p>The use of pharmaceuticals has grown substantially and their consequential release via wastewaters poses a potential threat to aquatic and terrestrial environments. While transportation prediction models for aquatic environments are well established, they cannot be universally extrapolated to terrestrial systems. Pharmaceuticals and their metabolites are, for example, readily detected in the excreta of terrestrial organisms (including humans). Furthermore, the trophic transfer of pharmaceuticals to and from food webs is often overlooked, which in turn highlights a public health concern and emphasizes the pressing need to elucidate how today's potpourri of pharmaceuticals affect the terrestrial system, their biophysical behaviors, and their interactions with soil metazoans. This review explores the existing knowledge base of pharmaceutical exposure sources, mobility, persistence, (bio)availability, (bio)accumulation, (bio)magnification, and trophic transfer of pharmaceuticals through the soil and terrestrial food chains.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":11.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124646","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 : 2024-09-03 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":11.2,"publicationDate":"2024-09-03","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
PROTACs as Therapeutic Modalities for Drug Discovery in Castration-Resistant Prostate Cancer. PROTACs 作为阉割耐药前列腺癌药物发现的治疗模式。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-08-08 DOI: 10.1146/annurev-pharmtox-030624-110238
Ling-Yu Wang, Chiu-Lien Hung, Tsan-Chun Wang, Hung-Chih Hsu, Hsing-Jien Kung, Kwang-Huei Lin
{"title":"PROTACs as Therapeutic Modalities for Drug Discovery in Castration-Resistant Prostate Cancer.","authors":"Ling-Yu Wang, Chiu-Lien Hung, Tsan-Chun Wang, Hung-Chih Hsu, Hsing-Jien Kung, Kwang-Huei Lin","doi":"10.1146/annurev-pharmtox-030624-110238","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-030624-110238","url":null,"abstract":"<p><p>Castration-resistant prostate cancer (CRPC) presents significant challenges in clinical management due to its resistance to conventional androgen receptor (AR)-targeting therapies. The advent of proteolysis targeting chimeras (PROTACs) has revolutionized cancer therapy by enabling the targeted degradation of key molecular players implicated in CRPC progression. In this review we discuss the developments of PROTACs for CRPC treatment, focusing on AR and other CRPC-associated regulators. We provide an overview of the strategic trends in AR PROTAC development from the aspect of targeting site selection and preclinical antitumor evaluation, as well as updates on AR degraders in clinical applications. Additionally, we briefly address the current status of selective AR degrader development. Furthermore, we review new developments in PROTACs as potential CRPC treatment paradigms, highlighting those targeting chromatin modulators BRD4, EZH2, and SWI/SNF; transcription regulator SMAD3; and kinases CDK9 and PIM1. Given the molecular targets shared between CRPC and neuroendocrine prostate cancer (NEPC), we also discuss the potential of PROTACs in addressing NEPC.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":11.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905651","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
Pharma[e]cology: How the Gut Microbiome Contributes to Variations in Drug Response. 制药学：肠道微生物组如何导致药物反应的变化。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-08-06 DOI: 10.1146/annurev-pharmtox-022724-100847
Kai R Trepka, Christine A Olson, Vaibhav Upadhyay, Chen Zhang, Peter J Turnbaugh
{"title":"Pharma[e]cology: How the Gut Microbiome Contributes to Variations in Drug Response.","authors":"Kai R Trepka, Christine A Olson, Vaibhav Upadhyay, Chen Zhang, Peter J Turnbaugh","doi":"10.1146/annurev-pharmtox-022724-100847","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-022724-100847","url":null,"abstract":"<p><p>Drugs represent our first, and sometimes last, line of defense for many diseases, yet despite decades of research we still do not fully understand why a given drug works in one patient and fails in the next. The human gut microbiome is one of the missing puzzle pieces, due to its ability to parallel and extend host pathways for drug metabolism, along with more complex host-microbiome interactions. Herein, we focus on the well-established links between the gut microbiome and drugs for heart disease and cancer, plus emerging data on neurological disease. We highlight the interdisciplinary methods that are available and how they can be used to address major remaining knowledge gaps, including the consequences of microbial drug metabolism for treatment outcomes. Continued progress in this area promises fundamental biological insights into humans and their associated microbial communities and strategies for leveraging the microbiome to improve the practice of medicine.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":11.2,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896608","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
What Structural Biology Tells Us About the Mode of Action and Detection of Toxicants. 结构生物学告诉我们毒物的作用方式和检测方法。
IF 11.2 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-08-06 DOI: 10.1146/annurev-pharmtox-061724-080642
Albane le Maire, William Bourguet
{"title":"What Structural Biology Tells Us About the Mode of Action and Detection of Toxicants.","authors":"Albane le Maire, William Bourguet","doi":"10.1146/annurev-pharmtox-061724-080642","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-061724-080642","url":null,"abstract":"<p><p>The study of the adverse effects of chemical substances on living organisms is an old and intense field of research. However, toxicological and environmental health sciences have long been dominated by descriptive approaches that enable associations or correlations but relatively few robust causal links and molecular mechanisms. Recent achievements have shown that structural biology approaches can bring this added value to the field. By providing atomic-level information, structural biology is a powerful tool to decipher the mechanisms by which toxicants bind to and alter the normal function of essential cell components, causing adverse effects. Here, using endocrine-disrupting chemicals as illustrative examples, we describe recent advances in the structure-based understanding of their modes of action and how this knowledge can be exploited to develop computational tools aimed at predicting properties of large collections of compounds.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":11.2,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896609","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
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 : 2024-08-02 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":11.2,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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