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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 : 2024-10-09 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"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":null,"pages":null},"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
Balancing immune activation with Itk. 用 Itk 平衡免疫激活。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 DOI: 10.1016/j.tips.2024.09.005
Zenia Kaul, Pamela L Schwartzberg
{"title":"Balancing immune activation with Itk.","authors":"Zenia Kaul, Pamela L Schwartzberg","doi":"10.1016/j.tips.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.tips.2024.09.005","url":null,"abstract":"<p><p>Development of protective immune responses relies on a balance between proinflammatory CD4 T helper (Th) cell populations such as Th17 cells and regulatory CD4 T cells (Tregs) that keep immune activation in check. Evidence that interleukin-2-inducible T cell kinase (Itk) regulates this balance supports therapeutic applications for Itk inhibition.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366579","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 can quantum computing be applied in clinical trial design and optimization? 如何将量子计算应用于临床试验设计和优化？
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 Epub Date: 2024-09-23 DOI: 10.1016/j.tips.2024.08.005
Hakan Doga, Aritra Bose, M Emre Sahin, Joao Bettencourt-Silva, Anh Pham, Eunyoung Kim, Alan Andress, Sudhir Saxena, Laxmi Parida, Jan Lukas Robertus, Hideaki Kawaguchi, Radwa Soliman, Daniel Blankenberg
{"title":"How can quantum computing be applied in clinical trial design and optimization?","authors":"Hakan Doga, Aritra Bose, M Emre Sahin, Joao Bettencourt-Silva, Anh Pham, Eunyoung Kim, Alan Andress, Sudhir Saxena, Laxmi Parida, Jan Lukas Robertus, Hideaki Kawaguchi, Radwa Soliman, Daniel Blankenberg","doi":"10.1016/j.tips.2024.08.005","DOIUrl":"10.1016/j.tips.2024.08.005","url":null,"abstract":"<p><p>Clinical trials are necessary for assessing the safety and efficacy of treatments. However, trial timelines are severely delayed with minimal success due to a multitude of factors, including imperfect trial site selection, cohort recruitment challenges, lack of efficacy, absence of reliable biomarkers, etc. Each of these factors possesses a unique computational challenge, such as data management, trial simulations, statistical analyses, and trial optimization. Recent advancements in quantum computing offer a promising opportunity to overcome these hurdles. In this opinion we uniquely explore the application of quantum optimization and quantum machine learning (QML) to the design and execution of clinical trials. We examine the current capabilities and limitations of quantum computing and outline its potential to streamline clinical trials.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354508","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
Neurofilament light chain as a biomarker of chemotherapy-induced peripheral neuropathy. 作为化疗诱发周围神经病变生物标志物的神经丝蛋白轻链
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 Epub Date: 2024-09-05 DOI: 10.1016/j.tips.2024.08.001
Nanna E Andersen, Wolfgang Boehmerle, Petra Huehnchen, Tore B Stage
{"title":"Neurofilament light chain as a biomarker of chemotherapy-induced peripheral neuropathy.","authors":"Nanna E Andersen, Wolfgang Boehmerle, Petra Huehnchen, Tore B Stage","doi":"10.1016/j.tips.2024.08.001","DOIUrl":"10.1016/j.tips.2024.08.001","url":null,"abstract":"<p><p>Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. The frequency of CIPN ranges from one in three to almost all patients depending on type of chemotherapy and dose. It causes symptoms that can range from sensitivity to touch and numbness to neuropathic pain in hands and feet. CIPN is notoriously difficult to grade objectively and has mostly relied on a clinician- or patient-based rating that is subjective and poorly reproducible. Thus, considerable effort has been aimed at identifying objective biomarkers of CIPN. Recent in vitro, animal, and clinical studies suggest that neurofilament light chain (NFL), a structural neuronal protein, may be an objective biomarker of CIPN. NFL released from cells to cell culture media reflects in vitro neurotoxicity, while NFL in serum reflects neuronal damage caused by chemotherapy in rodent models. Finally, NFL in serum may be a diagnostic biomarker of CIPN, but its prognostic ability to predict CIPN requires prospective evaluation. We discuss current limitations and future perspectives on the use of NFL as a preclinical and clinical biomarker of CIPN.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146303","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 TRPM channels for cerebral ischemia-reperfusion injury. 针对脑缺血再灌注损伤的 TRPM 通道。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 Epub Date: 2024-07-16 DOI: 10.1016/j.tips.2024.06.005
Dai-Qiang Liu, Wei Mei, Ya-Qun Zhou, Hong Xi
{"title":"Targeting TRPM channels for cerebral ischemia-reperfusion injury.","authors":"Dai-Qiang Liu, Wei Mei, Ya-Qun Zhou, Hong Xi","doi":"10.1016/j.tips.2024.06.005","DOIUrl":"10.1016/j.tips.2024.06.005","url":null,"abstract":"<p><p>Transient receptor potential melastatin (TRPM) channels have emerged as potential therapeutic targets for cerebral ischemia-reperfusion (I/R) injury. We highlight recent findings on the involvement of TRPM channels in oxidative stress, mitochondrial dysfunction, inflammation, and calcium overload. We also discuss the challenges and future directions in targeting TRPM channels for cerebral I/R injury.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634629","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
Spare the pain for your gut Treg cells! 让你的肠道 Treg 细胞免受痛苦！
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 Epub Date: 2024-09-05 DOI: 10.1016/j.tips.2024.08.008
Manon Defaye, Christophe Altier
{"title":"Spare the pain for your gut Treg cells!","authors":"Manon Defaye, Christophe Altier","doi":"10.1016/j.tips.2024.08.008","DOIUrl":"10.1016/j.tips.2024.08.008","url":null,"abstract":"<p><p>Maintaining gut homeostasis requires a complex interplay between the nervous and immune systems and the microbiome, but the nature of their interactions remains unclear. Chiu and Benoist's teams employed designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetics to target specific neuronal cell types and evaluate their effects on both the gut immune system and the microbiota.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146304","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
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 : 2024-10-01 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","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
Metabolic regulation in normal and leukemic stem cells 正常干细胞和白血病干细胞的代谢调节
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-09-20 DOI: 10.1016/j.tips.2024.08.004
Cheuk-Him Man, Changzheng Li, Xi Xu, Meng Zhao
{"title":"Metabolic regulation in normal and leukemic stem cells","authors":"Cheuk-Him Man, Changzheng Li, Xi Xu, Meng Zhao","doi":"10.1016/j.tips.2024.08.004","DOIUrl":"https://doi.org/10.1016/j.tips.2024.08.004","url":null,"abstract":"<p>Hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) are crucial for ensuring hematopoietic homeostasis and driving leukemia progression, respectively. Recent research has revealed that metabolic adaptations significantly regulate the function and survival of these stem cells. In this review, we provide an overview of how metabolic pathways regulate oxidative and proteostatic stresses in HSCs during homeostasis and aging. Furthermore, we highlight targetable metabolic pathways and explore their interactions with epigenetics and the microenvironment in addressing the chemoresistance and immune evasion capacities of LSCs. The metabolic differences between HSCs and LSCs have profound implications for therapeutic strategies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264601","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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