Signal Transduction and Targeted Therapy最新文献_第3页

Opioid receptors: single molecule studies shed light on mechanisms of efficacy 阿片受体：单分子研究揭示药效机制

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-08-30 DOI: 10.1038/s41392-024-01920-2

Cornelius Krasel, Moritz Bünemann

引用次数: 0

Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances 疾病中的三级淋巴结构：免疫机制与治疗进展

IF 39.3 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-08-28 DOI: 10.1038/s41392-024-01947-5

Lianyu Zhao, Song Jin, Shengyao Wang, Zhe Zhang, Xuan Wang, Zhanwei Chen, Xiaohui Wang, Shengyun Huang, Dongsheng Zhang, Haiwei Wu

{"title":"Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances","authors":"Lianyu Zhao, Song Jin, Shengyao Wang, Zhe Zhang, Xuan Wang, Zhanwei Chen, Xiaohui Wang, Shengyun Huang, Dongsheng Zhang, Haiwei Wu","doi":"10.1038/s41392-024-01947-5","DOIUrl":"https://doi.org/10.1038/s41392-024-01947-5","url":null,"abstract":"Tertiary lymphoid structures (TLSs) are defined as lymphoid aggregates formed in non-hematopoietic organs under pathological conditions. Similar to secondary lymphoid organs (SLOs), the formation of TLSs relies on the interaction between lymphoid tissue inducer (LTi) cells and lymphoid tissue organizer (LTo) cells, involving multiple cytokines. Heterogeneity is a distinguishing feature of TLSs, which may lead to differences in their functions. Growing evidence suggests that TLSs are associated with various diseases, such as cancers, autoimmune diseases, transplant rejection, chronic inflammation, infection, and even ageing. However, the detailed mechanisms behind these clinical associations are not yet fully understood. The mechanisms by which TLS maturation and localization affect immune function are also unclear. Therefore, it is necessary to enhance the understanding of TLS development and function at the cellular and molecular level, which may allow us to utilize them to improve the immune microenvironment. In this review, we delve into the composition, formation mechanism, associations with diseases, and potential therapeutic applications of TLSs. Furthermore, we discuss the therapeutic implications of TLSs, such as their role as markers of therapeutic response and prognosis. Finally, we summarize various methods for detecting and targeting TLSs. Overall, we provide a comprehensive understanding of TLSs and aim to develop more effective therapeutic strategies.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":39.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085704","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

Enhancing RBD exposure and S1 shedding by an extremely conserved SARS-CoV-2 NTD epitope. 通过极其保守的 SARS-CoV-2 NTD 表位增强 RBD 暴露和 S1 脱落。

IF 40.8 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-08-28 DOI: 10.1038/s41392-024-01940-y

Qianhui Zhu, Pan Liu, Shuo Liu, Can Yue, Xiangxi Wang

引用次数: 0

Hyperuricemia and its related diseases: mechanisms and advances in therapy. 高尿酸血症及其相关疾病：治疗机制与进展。

IF 40.8 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-08-28 DOI: 10.1038/s41392-024-01916-y

Lin Du, Yao Zong, Haorui Li, Qiyue Wang, Lei Xie, Bo Yang, Yidan Pang, Changqing Zhang, Zhigang Zhong, Junjie Gao

{"title":"Hyperuricemia and its related diseases: mechanisms and advances in therapy.","authors":"Lin Du, Yao Zong, Haorui Li, Qiyue Wang, Lei Xie, Bo Yang, Yidan Pang, Changqing Zhang, Zhigang Zhong, Junjie Gao","doi":"10.1038/s41392-024-01916-y","DOIUrl":"10.1038/s41392-024-01916-y","url":null,"abstract":"Hyperuricemia, characterized by elevated levels of serum uric acid (SUA), is linked to a spectrum of commodities such as gout, cardiovascular diseases, renal disorders, metabolic syndrome, and diabetes, etc. Significantly impairing the quality of life for those affected, the prevalence of hyperuricemia is an upward trend globally, especially in most developed countries. UA possesses a multifaceted role, such as antioxidant, pro-oxidative, pro-inflammatory, nitric oxide modulating, anti-aging, and immune effects, which are significant in both physiological and pathological contexts. The equilibrium of circulating urate levels hinges on the interplay between production and excretion, a delicate balance orchestrated by urate transporter functions across various epithelial tissues and cell types. While existing research has identified hyperuricemia involvement in numerous biological processes and signaling pathways, the precise mechanisms connecting elevated UA levels to disease etiology remain to be fully elucidated. In addition, the influence of genetic susceptibilities and environmental determinants on hyperuricemia calls for a detailed and nuanced examination. This review compiles data from global epidemiological studies and clinical practices, exploring the physiological processes and the genetic foundations of urate transporters in depth. Furthermore, we uncover the complex mechanisms by which the UA induced inflammation influences metabolic processes in individuals with hyperuricemia and the association with its relative disease, offering a foundation for innovative therapeutic approaches and advanced pharmacological strategies.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":40.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081465","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

Predicting gastric cancer response to anti-HER2 therapy or anti-HER2 combined immunotherapy based on multi-modal data. 基于多模态数据预测胃癌对抗 HER2 治疗或抗 HER2 联合免疫疗法的反应。

IF 40.8 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-08-26 DOI: 10.1038/s41392-024-01932-y

Zifan Chen, Yang Chen, Yu Sun, Lei Tang, Li Zhang, Yajie Hu, Meng He, Zhiwei Li, Siyuan Cheng, Jiajia Yuan, Zhenghang Wang, Yakun Wang, Jie Zhao, Jifang Gong, Liying Zhao, Baoshan Cao, Guoxin Li, Xiaotian Zhang, Bin Dong, Lin Shen

{"title":"Predicting gastric cancer response to anti-HER2 therapy or anti-HER2 combined immunotherapy based on multi-modal data.","authors":"Zifan Chen, Yang Chen, Yu Sun, Lei Tang, Li Zhang, Yajie Hu, Meng He, Zhiwei Li, Siyuan Cheng, Jiajia Yuan, Zhenghang Wang, Yakun Wang, Jie Zhao, Jifang Gong, Liying Zhao, Baoshan Cao, Guoxin Li, Xiaotian Zhang, Bin Dong, Lin Shen","doi":"10.1038/s41392-024-01932-y","DOIUrl":"10.1038/s41392-024-01932-y","url":null,"abstract":"The sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P < 0.05). These findings not only highlight the significance of multi-modal data analysis in enhancing treatment evaluation and personalized medicine for HER2-positive gastric cancer, but also the potential and clinical value of our model.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":40.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056470","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

An emerging artificial nanomachine: a nanoengine with a reversible clutch. 一种新兴的人造纳米机械：带有可逆离合器的纳米发动机。

IF 40.8 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-08-26 DOI: 10.1038/s41392-024-01919-9

Ziqi Fang, Jianxin Jiang, Min Wu

引用次数: 0

Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. 阿尔茨海默病的最新进展：机制、临床试验和新药开发战略。

IF 40.8 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-08-23 DOI: 10.1038/s41392-024-01911-3

Jifa Zhang, Yinglu Zhang, Jiaxing Wang, Yilin Xia, Jiaxian Zhang, Lei Chen

{"title":"Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.","authors":"Jifa Zhang, Yinglu Zhang, Jiaxing Wang, Yilin Xia, Jiaxian Zhang, Lei Chen","doi":"10.1038/s41392-024-01911-3","DOIUrl":"10.1038/s41392-024-01911-3","url":null,"abstract":"Alzheimer's disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate and diverse, stemming from a combination of factors such as aging, genetics, and environment. Our current understanding of AD pathologies involves various hypotheses, such as the cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, and abnormal autophagy. Nonetheless, unraveling the interplay among these pathological aspects and pinpointing the primary initiators of AD require further elucidation and validation. In the past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available drugs primarily offer symptomatic relief and often accompanied by undesirable side effects. However, recent approvals of aducanumab (1) and lecanemab (2) by the Food and Drug Administration (FDA) present the potential in disrease-modifying effects. Nevertheless, the long-term efficacy and safety of these drugs need further validation. Consequently, the quest for safer and more effective AD drugs persists as a formidable and pressing task. This review discusses the current understanding of AD pathogenesis, advances in diagnostic biomarkers, the latest updates of clinical trials, and emerging technologies for AD drug development. We highlight recent progress in the discovery of selective inhibitors, dual-target inhibitors, allosteric modulators, covalent inhibitors, proteolysis-targeting chimeras (PROTACs), and protein-protein interaction (PPI) modulators. Our goal is to provide insights into the prospective development and clinical application of novel AD drugs.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":40.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036910","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

Annexin A1 binds PDZ and LIM domain 7 to inhibit adipogenesis and prevent obesity. Annexin A1 可与 PDZ 和 LIM domain 7 结合，抑制脂肪生成，预防肥胖。

IF 40.8 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-08-23 DOI: 10.1038/s41392-024-01930-0

Lu Fang, Changjie Liu, Zong-Zhe Jiang, Mengxiao Wang, Kang Geng, Yangkai Xu, Yujie Zhu, Yiwen Fu, Jing Xue, Wenxin Shan, Qi Zhang, Jie Chen, Jiahong Chen, Mingming Zhao, Yuxuan Guo, K W Michael Siu, Y Eugene Chen, Yong Xu, Donghui Liu, Lemin Zheng

{"title":"Annexin A1 binds PDZ and LIM domain 7 to inhibit adipogenesis and prevent obesity.","authors":"Lu Fang, Changjie Liu, Zong-Zhe Jiang, Mengxiao Wang, Kang Geng, Yangkai Xu, Yujie Zhu, Yiwen Fu, Jing Xue, Wenxin Shan, Qi Zhang, Jie Chen, Jiahong Chen, Mingming Zhao, Yuxuan Guo, K W Michael Siu, Y Eugene Chen, Yong Xu, Donghui Liu, Lemin Zheng","doi":"10.1038/s41392-024-01930-0","DOIUrl":"10.1038/s41392-024-01930-0","url":null,"abstract":"Obesity is a global issue that warrants the identification of more effective therapeutic targets and a better understanding of the pivotal molecular pathogenesis. Annexin A1 (ANXA1) is known to inhibit phospholipase A2, exhibiting anti-inflammatory activity. However, the specific effects of ANXA1 in obesity and the underlying mechanisms of action remain unclear. Our study reveals that ANXA1 levels are elevated in the adipose tissue of individuals with obesity. Whole-body or adipocyte-specific ANXA1 deletion aggravates obesity and metabolic disorders. ANXA1 levels are higher in stromal vascular fractions (SVFs) than in mature adipocytes. Further investigation into the role of ANXA1 in SVFs reveals that ANXA1 overexpression induces lower numbers of mature adipocytes, while ANXA1-knockout SVFs exhibit the opposite effect. This suggests that ANXA1 plays an important role in adipogenesis. Mechanistically, ANXA1 competes with MYC binding protein 2 (MYCBP2) for interaction with PDZ and LIM domain 7 (PDLIM7). This exposes the MYCBP2-binding site, allowing it to bind more readily to the SMAD family member 4 (SMAD4) and promoting its ubiquitination and degradation. SMAD4 degradation downregulates peroxisome proliferator-activated receptor gamma (PPARγ) transcription and reduces adipogenesis. Treatment with Ac2-26, an active peptide derived from ANXA1, inhibits both adipogenesis and obesity through the mechanism. In conclusion, the molecular mechanism of ANXA1 inhibiting adipogenesis was first uncovered in our study, which is a potential target for obesity prevention and treatment.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":40.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036909","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

MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer. MYC 和 KRAS 的合作：从历史挑战到癌症治疗机遇。

IF 40.8 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-08-21 DOI: 10.1038/s41392-024-01907-z

Sílvia Casacuberta-Serra, Íñigo González-Larreategui, Daniel Capitán-Leo, Laura Soucek

{"title":"MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer.","authors":"Sílvia Casacuberta-Serra, Íñigo González-Larreategui, Daniel Capitán-Leo, Laura Soucek","doi":"10.1038/s41392-024-01907-z","DOIUrl":"10.1038/s41392-024-01907-z","url":null,"abstract":"RAS and MYC rank amongst the most commonly altered oncogenes in cancer, with RAS being the most frequently mutated and MYC the most amplified. The cooperative interplay between RAS and MYC constitutes a complex and multifaceted phenomenon, profoundly influencing tumor development. Together and individually, these two oncogenes regulate most, if not all, hallmarks of cancer, including cell death escape, replicative immortality, tumor-associated angiogenesis, cell invasion and metastasis, metabolic adaptation, and immune evasion. Due to their frequent alteration and role in tumorigenesis, MYC and RAS emerge as highly appealing targets in cancer therapy. However, due to their complex nature, both oncogenes have been long considered \"undruggable\" and, until recently, no drugs directly targeting them had reached the clinic. This review aims to shed light on their complex partnership, with special attention to their active collaboration in fostering an immunosuppressive milieu and driving immunotherapeutic resistance in cancer. Within this review, we also present an update on the different inhibitors targeting RAS and MYC currently undergoing clinical trials, along with their clinical outcomes and the different combination strategies being explored to overcome drug resistance. This recent clinical development suggests a paradigm shift in the long-standing belief of RAS and MYC \"undruggability\", hinting at a new era in their therapeutic targeting.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":40.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009403","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

The JAK-STAT pathway: from structural biology to cytokine engineering. JAK-STAT 通路：从结构生物学到细胞因子工程学。

IF 40.8 1区医学

Signal Transduction and Targeted Therapy Pub Date : 2024-08-21 DOI: 10.1038/s41392-024-01934-w

You Lv, Jianxun Qi, Jeffrey J Babon, Longxing Cao, Guohuang Fan, Jiajia Lang, Jin Zhang, Pengbing Mi, Bostjan Kobe, Faming Wang

{"title":"The JAK-STAT pathway: from structural biology to cytokine engineering.","authors":"You Lv, Jianxun Qi, Jeffrey J Babon, Longxing Cao, Guohuang Fan, Jiajia Lang, Jin Zhang, Pengbing Mi, Bostjan Kobe, Faming Wang","doi":"10.1038/s41392-024-01934-w","DOIUrl":"10.1038/s41392-024-01934-w","url":null,"abstract":"The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway serves as a paradigm for signal transduction from the extracellular environment to the nucleus. It plays a pivotal role in physiological functions, such as hematopoiesis, immune balance, tissue homeostasis, and surveillance against tumors. Dysregulation of this pathway may lead to various disease conditions such as immune deficiencies, autoimmune diseases, hematologic disorders, and cancer. Due to its critical role in maintaining human health and involvement in disease, extensive studies have been conducted on this pathway, ranging from basic research to medical applications. Advances in the structural biology of this pathway have enabled us to gain insights into how the signaling cascade operates at the molecular level, laying the groundwork for therapeutic development targeting this pathway. Various strategies have been developed to restore its normal function, with promising therapeutic potential. Enhanced comprehension of these molecular mechanisms, combined with advances in protein engineering methodologies, has allowed us to engineer cytokines with tailored properties for targeted therapeutic applications, thereby enhancing their efficiency and safety. In this review, we outline the structural basis that governs key nodes in this pathway, offering a comprehensive overview of the signal transduction process. Furthermore, we explore recent advances in cytokine engineering for therapeutic development in this pathway.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":null,"pages":null},"PeriodicalIF":40.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018513","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