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Trends in pharmacological sciences最新文献

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TAM-tastic: from resistance to resilience in cancer. TAM-tastic：癌症从抗药性到恢复力。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-01 DOI: 10.1016/j.tips.2024.09.006
Jie Ting Low, Ping-Chih Ho, Mai Matsushita
{"title":"TAM-tastic: from resistance to resilience in cancer.","authors":"Jie Ting Low, Ping-Chih Ho, Mai Matsushita","doi":"10.1016/j.tips.2024.09.006","DOIUrl":"10.1016/j.tips.2024.09.006","url":null,"abstract":"<p><p>Overcoming resistance to immunotherapy in cancer is challenging due, in part, to tumor-associated macrophages (TAMs) co-expressing T cell immunoglobulin and mucin domain-containing 3 (TIM3) and V-domain immunoglobulin suppressor of T cell activation (VISTA) in tumor microenvironments (TME) with sparse T cell infiltration. In a recent article, Vanmeerbeek et al. found that blocking TIM3 or VISTA on IL-4-supported TAMs, in combination with paclitaxel (PTX), reprogrammed TAMs to attack cancer cells, highlighting a potential new therapeutic strategy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"953-954"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366580","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
Nitro-fatty acids: promising agents for the development of new cancer therapeutics. 硝基脂肪酸：开发癌症新疗法的有望药物。
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.2024.09.009
Jessica Roos, Georg Manolikakes, Uwe Schlomann, Anna Klinke, Francisco J Schopfer, Carola A Neumann, Thorsten J Maier
{"title":"Nitro-fatty acids: promising agents for the development of new cancer therapeutics.","authors":"Jessica Roos, Georg Manolikakes, Uwe Schlomann, Anna Klinke, Francisco J Schopfer, Carola A Neumann, Thorsten J Maier","doi":"10.1016/j.tips.2024.09.009","DOIUrl":"10.1016/j.tips.2024.09.009","url":null,"abstract":"<p><p>Nitro-fatty acids (NO<sub>2</sub>-FAs) are endogenous pleiotropic lipid mediators regarded as promising drug candidates for treating inflammatory and fibrotic diseases. Over the past two decades, the anti-inflammatory and cytoprotective actions of NO<sub>2</sub>-FAs and several molecular targets have been identified. More recently, preclinical studies have demonstrated their potential as prospective cancer therapeutics with favorable safety and tumor-selective profiles. In this review, we describe the mechanisms of action, with a focus on NO<sub>2</sub>-FA antineoplastic and chemosensitizing effects. We also address the potential therapeutic applications of endogenous and structurally modified NO<sub>2</sub>-FAs species in cancer treatment.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1061-1080"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569160","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
Advances in triterpene drug discovery. 三萜类药物发现的进展。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-30 DOI: 10.1016/j.tips.2024.10.003
Zoë R Goddard, Mark Searcey, Anne Osbourn
{"title":"Advances in triterpene drug discovery.","authors":"Zoë R Goddard, Mark Searcey, Anne Osbourn","doi":"10.1016/j.tips.2024.10.003","DOIUrl":"10.1016/j.tips.2024.10.003","url":null,"abstract":"<p><p>Triterpenes are structurally complex natural products with promising therapeutic properties. Recalcitrance to chemical synthesis has hindered their use in drug development. Recent advances now make it possible to access and harness triterpene structural diversity using engineering biology approaches, enabling the discovery and optimisation of a new generation of drug leads.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"964-968"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558868","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
MICUs protect the heart by regulating mitochondrial calcium. MICU 通过调节线粒体钙质来保护心脏。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI: 10.1016/j.tips.2024.09.010
Ulas Ozkurede, Shanmugasundaram Pakkiriswami, Julia C Liu
{"title":"MICUs protect the heart by regulating mitochondrial calcium.","authors":"Ulas Ozkurede, Shanmugasundaram Pakkiriswami, Julia C Liu","doi":"10.1016/j.tips.2024.09.010","DOIUrl":"10.1016/j.tips.2024.09.010","url":null,"abstract":"<p><p>Regulation of mitochondrial calcium uptake by the mitochondrial calcium uniporter (mtCU) complex is crucial for heart function. In a recent study, Hasan et al. demonstrated that mitochondrial calcium uptake (MICU)1 and MICU2, regulatory subunits of the complex, help maintain calcium homeostasis in cardiac mitochondria, providing potential targets for therapies aimed at improving mitochondrial function in heart disease.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"950-952"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475600","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
Phenotypic approaches for CNS drugs. 中枢神经系统药物的表型方法。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-21 DOI: 10.1016/j.tips.2024.09.003
Raahul Sharma, Caitlin R M Oyagawa, Hamid Abbasi, Michael Dragunow, Daniel Conole
{"title":"Phenotypic approaches for CNS drugs.","authors":"Raahul Sharma, Caitlin R M Oyagawa, Hamid Abbasi, Michael Dragunow, Daniel Conole","doi":"10.1016/j.tips.2024.09.003","DOIUrl":"10.1016/j.tips.2024.09.003","url":null,"abstract":"<p><p>Central nervous system (CNS) drug development is plagued by high clinical failure rate. Phenotypic assays promote clinical translation of drugs by reducing complex brain diseases to measurable, clinically valid phenotypes. We critique recent platforms integrating patient-derived brain cells, which most accurately recapitulate CNS disease phenotypes, with higher throughput models, including immortalized cells, to balance validity and scalability. These platforms were screened with conventional commercial chemogenomic compound libraries. We explore emerging library curation strategies to improve hit rate and quality, and screening novel fragment libraries as alternatives, for more tractable drug target deconvolution. The clinically relevant models used in these platforms could harbor important, unidentified drug targets, so we review evolving agnostic target deconvolution approaches, including chemical proteomics and artificial intelligence (AI), which aid in phenotypic screening hit mechanism elucidation, thereby facilitating rational hit-to-drug optimization.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"997-1017"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508709","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
Novel antagonists reveal the mechanism of PXR inhibition. 新型拮抗剂揭示了 PXR 的抑制机制。
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.2024.10.002
Rajamanikkam Kamaraj, Petr Pavek
{"title":"Novel antagonists reveal the mechanism of PXR inhibition.","authors":"Rajamanikkam Kamaraj, Petr Pavek","doi":"10.1016/j.tips.2024.10.002","DOIUrl":"10.1016/j.tips.2024.10.002","url":null,"abstract":"<p><p>The pregnane X receptor (PXR) is a key regulator of metabolism, but the mechanisms underlying its antagonism remain unclear. Garcia-Maldonado et al. reported potent new antagonists and their co-crystal structures, revealing molecular determinants of PXR antagonism and paving the way for developing antagonists as therapeutics and preventing undesirable PXR activation.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"961-963"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475602","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
Advancing cancer research. 推进癌症研究。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-30 DOI: 10.1016/j.tips.2024.10.004
Cornelius Y Taabazuing, Whitney S Henry, Michael U J Oliphant, Shamara S Lawrence
{"title":"Advancing cancer research.","authors":"Cornelius Y Taabazuing, Whitney S Henry, Michael U J Oliphant, Shamara S Lawrence","doi":"10.1016/j.tips.2024.10.004","DOIUrl":"10.1016/j.tips.2024.10.004","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"943-949"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547653","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
DOT1L: orchestrating methylation-dependent radiotheRAPy responses via BRCA1. DOT1L：通过 BRCA1 协调甲基化依赖性放射反应。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-09 DOI: 10.1016/j.tips.2024.09.008
Justin W Leung, Kyle M Miller
{"title":"DOT1L: orchestrating methylation-dependent radiotheRAPy responses via BRCA1.","authors":"Justin W Leung, Kyle M Miller","doi":"10.1016/j.tips.2024.09.008","DOIUrl":"10.1016/j.tips.2024.09.008","url":null,"abstract":"<p><p>Breast Cancer Type 1 Susceptibility Protein (BRCA)-1 existing in several functionally distinct complexes, promotes DNA repair of DNA double-strand breaks (DSBs). A recent study by Tang and colleagues identifies the lysine methyltransferase Disruptor of Telomeric Silencing 1-Like (DOT1L) involved in modifying Receptor-Associated Protein 80 (RAP80) to promote BRCA1-A complex localization and repair functions at DNA breaks. This study illuminates a potential therapeutic target for cancer radiotherapy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"955-957"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401423","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 white adipose tissue to combat insulin resistance. 以白色脂肪组织为目标，对抗胰岛素抵抗。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 Epub Date: 2024-07-24 DOI: 10.1016/j.tips.2024.06.008
Yiheng Huang, Pingyi Gao, Lawrence H Young, Dake Qi
{"title":"Targeting white adipose tissue to combat insulin resistance.","authors":"Yiheng Huang, Pingyi Gao, Lawrence H Young, Dake Qi","doi":"10.1016/j.tips.2024.06.008","DOIUrl":"10.1016/j.tips.2024.06.008","url":null,"abstract":"<p><p>Metabolic and endocrine dysfunction of white adipose tissue (WAT) is linked to inflammation, which has been considered a key mechanism of insulin resistance (IR). However, recent studies revealed non-inflammatory mechanisms of IR in WAT, which may trigger inflammation and could be developed as a novel strategy to counteract IR.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"868-871"},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761115","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
New insights into SYK targeting in solid tumors. 实体瘤中 SYK 靶向治疗的新见解。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 Epub Date: 2024-09-24 DOI: 10.1016/j.tips.2024.08.006
Shweta Joshi
{"title":"New insights into SYK targeting in solid tumors.","authors":"Shweta Joshi","doi":"10.1016/j.tips.2024.08.006","DOIUrl":"10.1016/j.tips.2024.08.006","url":null,"abstract":"<p><p>Spleen tyrosine kinase (SYK) is predominantly expressed in hematopoietic cells and has been extensively studied for its pivotal role in B cell malignancies and autoimmune diseases. In epithelial solid tumors, SYK shows a paradoxical role, acting as a tumor suppressor in some cancers while driving tumor growth in others. Recent preclinical studies have identified the role of SYK in the tumor microenvironment (TME), revealing that SYK signaling in immune cells, especially B cells, and myeloid cells, promote immunosuppression, tumor growth, and metastasis across various solid tumors. This review explores the emerging roles of SYK in solid tumors, the mechanisms of SYK activation, and findings from preclinical and clinical studies of SYK inhibitors as either standalone treatments or in combination with immunotherapy or chemotherapy for solid tumors.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"904-918"},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354509","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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