Pharmacology & Therapeutics最新文献_第2页

Next-generation nanocarriers for therapeutic oligonucleotides: Precision targeting and stimuli-responsive cancer therapy 用于治疗寡核苷酸的下一代纳米载体：精确靶向和刺激反应性癌症治疗

IF 12.5 1区医学

Pharmacology & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-11-19 DOI: 10.1016/j.pharmthera.2025.108960

Yantong Li , Mei Zhang , Junjie Gu , Yao He , Mi Zhou , Yunfeng Lin

{"title":"Next-generation nanocarriers for therapeutic oligonucleotides: Precision targeting and stimuli-responsive cancer therapy","authors":"Yantong Li , Mei Zhang , Junjie Gu , Yao He , Mi Zhou , Yunfeng Lin","doi":"10.1016/j.pharmthera.2025.108960","DOIUrl":"10.1016/j.pharmthera.2025.108960","url":null,"abstract":"<div><div>Therapeutic oligonucleotides (TOs) have emerged as a promising gene therapy approach for tumor treatment, offering high specificity and therapeutic efficacy by directly modulating target gene expression and subsequent protein synthesis. However, the clinical translation of TOs remains hindered by critical challenges, including suboptimal targeting efficiency, insufficient responsiveness, lysosomal entrapment, poor stability, and potential off-target effects. To address these limitations, advanced delivery systems with precise targeting and stimuli-responsive capabilities are essential. Nanocarrier systems, characterized by their high targeting precision and controlled drug release, have gained widespread application in tumor gene therapy. Integrating TOs with intelligent nanocarrier systems enables safe, stable, efficient, and targeted delivery to tumor tissues, presenting a highly promising strategy for precise cancer gene therapy. This review provides a comprehensive overview of current advancements in the design of intelligent nanoparticles for TOs delivery. It discusses the classification of TOs and their therapeutic mechanisms, the categorization of nanocarriers, the binding modes between TOs and nanomaterials, and strategies to achieve tumor-specific targeting and responsiveness. By addressing these critical design considerations, this review aims to inform the development of next-generation nanomaterials for improved TOs-based tumor therapy.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"277 ","pages":"Article 108960"},"PeriodicalIF":12.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553618","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

Treatment approaches for alcohol use disorder with metabolic dysfunction 酒精使用障碍伴代谢功能障碍的治疗方法

IF 12.5 1区医学

Pharmacology & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-11-12 DOI: 10.1016/j.pharmthera.2025.108957

Alexandra C. Wagner , Jeesun Jung , Pal Pacher , Falk.W. Lohoff

{"title":"Treatment approaches for alcohol use disorder with metabolic dysfunction","authors":"Alexandra C. Wagner , Jeesun Jung , Pal Pacher , Falk.W. Lohoff","doi":"10.1016/j.pharmthera.2025.108957","DOIUrl":"10.1016/j.pharmthera.2025.108957","url":null,"abstract":"<div><div>Alcohol use disorder (AUD) and alcohol excess contribute significantly to morbidity and mortality through their multisystem effects, particularly on liver health. When combined with metabolic dysfunction––defined as obesity, hypertension, type 2 diabetes, and dyslipidemia––alcohol consumption has additive and synergistic effects that are associated with liver disease progression and increased risk of cardiovascular, cancer-related, hepatic, and all-cause mortality. Despite growing recognition of these overlapping risk factors, there remains no universally accepted threshold for “safe” alcohol consumption, as individual vulnerability varies widely depending on genetic, metabolic, and environmental factors.</div><div>Individuals with co-occurring AUD and metabolic dysfunction face unique clinical challenges, yet current treatment frameworks rarely address this intersection. Existing pharmacologic and behavioral therapies for AUD are limited in efficacy and uptake, and they are often not tailored to the metabolic risks that accompany heavy drinking. This comorbid population represents an underrecognized group with clinical complexity and unmet therapeutic needs.</div><div>In this review, we synthesize current knowledge across hepatology, psychiatry, and addiction medicine to characterize the shared pathophysiology and comorbidities of <em>co-occurring AUD and metabolic dysfunction</em>. We examine mortality trends, highlight gaps in current treatment paradigms, and evaluate how emerging research and treatments for MASLD, MetALD, and ALD can inform more effective clinical care strategies. Our aim is to establish a more unified framework for understanding and treating individuals with co-occurring AUD and metabolic dysfunction.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"277 ","pages":"Article 108957"},"PeriodicalIF":12.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515797","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

Formylpeptide receptors: A novel target to treat cardiometabolic complications 甲酰基肽受体：治疗心脏代谢并发症的新靶点。

IF 12.5 1区医学

Pharmacology & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-10-26 DOI: 10.1016/j.pharmthera.2025.108941

Chen Huei Leo , Elizabeth A. Vecchio , Ting Fu , Xiangyan Yi , Cheng Peng , Peishen Zhao , Owen L. Woodman , Jonathan Baell , Rebecca H. Ritchie , Cheng Xue Qin

{"title":"Formylpeptide receptors: A novel target to treat cardiometabolic complications","authors":"Chen Huei Leo , Elizabeth A. Vecchio , Ting Fu , Xiangyan Yi , Cheng Peng , Peishen Zhao , Owen L. Woodman , Jonathan Baell , Rebecca H. Ritchie , Cheng Xue Qin","doi":"10.1016/j.pharmthera.2025.108941","DOIUrl":"10.1016/j.pharmthera.2025.108941","url":null,"abstract":"<div><div>The formylpeptide receptor (FPR) family, particularly FPR2, has emerged as a master regulator of inflammation and its resolution. Given that both cardiovascular diseases and metabolic disorders are characterised by pro-inflammatory scenarios, often with resultant impairment of the healing response to (i.e. resolution of) inflammation, therapeutic targeting of the FPR family with judicious agonist selection provides new promise for tackling cardiometabolic disease. Here, we consider the pharmacology of this intriguing receptor family, the potential for novel biased signalling at its receptor subtypes and the current status of both endogenous and synthetic agonists (including peptides/proteins, small molecules and lipids) reported to be active at FPRs. A detailed review of the therapeutic potential of published FPR ligands involved in regulating and resolving inflammation in cardiometabolic disease is also provided. We anticipate that a broader understanding of, and greater appreciation for, the translational potential of pro-resolution FPR-based therapies may offer new effective means of targeting a range of cardiometabolic disorders and their resultant complications.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"277 ","pages":"Article 108941"},"PeriodicalIF":12.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380788","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

Cell phenotypic conversion and fate change during the host defense response, tissue injury and repair 在宿主防御反应、组织损伤和修复过程中，细胞表型转换和命运改变

IF 12.5 1区医学

Pharmacology & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-11-18 DOI: 10.1016/j.pharmthera.2025.108959

Xin Shi , Gabriel Mekis , Kevin J. Simms , Bin Gao , Ping Zhang

{"title":"Cell phenotypic conversion and fate change during the host defense response, tissue injury and repair","authors":"Xin Shi , Gabriel Mekis , Kevin J. Simms , Bin Gao , Ping Zhang","doi":"10.1016/j.pharmthera.2025.108959","DOIUrl":"10.1016/j.pharmthera.2025.108959","url":null,"abstract":"<div><div>In the process of host response to insults of serious injury/intense stressor, many types of somatic cells can undergo phenotypic conversion and fate change. The typical feature of cell conversion in this circumstance is to acquire the status of upstream precursors, which commonly accompanies transcriptional alteration to enhance cell proliferation and increase the plasticity of differentiation toward the lineage(s) needed in urgency for defending host against injury as well as maintaining/restoring the integrity of organ tissue function. The extent of cell conversion varies dependent on cell types and insult properties. Pattern ligands derived from pathogens and damaged tissues as well as the dynamic changes in systemic neurohumoral environment and local niche cue mediate cell conversion. Distinctive signaling interplays are involved in regulating various types of cell conversion. Better understanding the phenomena of cell conversion and their underlying regulatory mechanisms is critical for advancing regenerative medicine and developing novel therapeutic strategies to promote host defense as well as optimal repair of organ tissue injury. This article reviews recent progress in investigation on cell conversion and state change in different organ tissue environments with focus on bone marrow, vascular endothelium, lung, liver, and intestine. Discussion on delineating the signaling mechanisms is extended. Efforts in exploring the correlated therapeutic approaches are addressed to highlight the substantial potential in clinical application for this field of regenerative medicine.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"277 ","pages":"Article 108959"},"PeriodicalIF":12.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553614","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

Corrigendum to “Drug discovery through biophysical techniques: Methods and applications” [pharmacology and therapeutics volume 277 (2026) 108947] “通过生物物理技术发现药物：方法和应用”的勘误表[药理学和治疗学卷277 (2026)108947]

IF 12.5 1区医学

Pharmacology & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-11-28 DOI: 10.1016/j.pharmthera.2025.108961

Yinhao Zhou, Haiyun Hu, Qiuyan Huang, Yuwei Tang, Yanli Liu

引用次数: 0

RNA renaissance: Harnessing non-coding RNA therapeutics for hepatocellular carcinoma RNA复兴：利用非编码RNA治疗肝癌

IF 12.5 1区医学

Pharmacology & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-11-12 DOI: 10.1016/j.pharmthera.2025.108956

Subhas Das , Soumyabrata Chatterjee , Tushar Patel , Soma Banerjee

{"title":"RNA renaissance: Harnessing non-coding RNA therapeutics for hepatocellular carcinoma","authors":"Subhas Das , Soumyabrata Chatterjee , Tushar Patel , Soma Banerjee","doi":"10.1016/j.pharmthera.2025.108956","DOIUrl":"10.1016/j.pharmthera.2025.108956","url":null,"abstract":"<div><div>Non-coding RNAs (ncRNAs) represent a diverse group of RNAs that exhibit an important role in various cellular mechanisms by regulating gene expression at both transcription and translation levels without being translated into proteins. Despite their canonical cellular functions, dysregulation of ncRNAs especially microRNAs (miRNAs), circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) have been widely documented in various diseases including cancer. Owing to their potential to regulate multiple genes and signaling pathways simultaneously, targeting individual ncRNA provides a multi-faceted therapeutic approach. Moreover, the liver's inherent ability for rapid uptake of systemically administered such ncRNAs-based therapy renders it as a suitable target for developing effective therapeutics for liver cancer. Here, we have conducted a meta<em>-</em>analysis of the published literature on miRNAs deregulated in HCC to uncover multifunctional miRNAs driving various oncogenic pathways corroborated by experimental validations as well. However, for therapeutic purposes, lncRNAs that sequester several such miRNAs have been also identified in HCC, highlighting them as promising targets for ncRNA-based therapy in HCC. Regardless of promising preclinical studies, very few ncRNA-based therapeutics have entered clinical trials. Therefore, recognizing these limitations, we have discussed the challenges impeding the development of ncRNA-based treatments along with some probable solutions.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"277 ","pages":"Article 108956"},"PeriodicalIF":12.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515653","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

A map of molecular drug targets and therapeutics for the US FDA-approved drugs: The impact of expedited regulatory pathways and first-in-class drug approvals on drug innovation 美国fda批准药物的分子药物靶点和治疗方法图：加速监管途径和首类药物批准对药物创新的影响

IF 12.5 1区医学

Pharmacology & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-11-02 DOI: 10.1016/j.pharmthera.2025.108945

Pitchai Balakumar , N.V.L. Sirisha Mulukuri , Gowraganahalli Jagadeesh

{"title":"A map of molecular drug targets and therapeutics for the US FDA-approved drugs: The impact of expedited regulatory pathways and first-in-class drug approvals on drug innovation","authors":"Pitchai Balakumar , N.V.L. Sirisha Mulukuri , Gowraganahalli Jagadeesh","doi":"10.1016/j.pharmthera.2025.108945","DOIUrl":"10.1016/j.pharmthera.2025.108945","url":null,"abstract":"<div><div>Despite advances in pharmaceutical innovation, there is a lack of insights into recent FDA drug approval trends, particularly concerning molecular targets, therapeutic areas, and diseases. Here, we map the molecular targets of 465 drugs approved by the US FDA from 2015 to 2024: 29% were biologics, 71% were NMEs, 50% targeted orphan diseases, and 41% were first-in-class drugs with novel mechanisms. Five major protein classes predominate as drug targets: enzymes (17%), kinases (16%), GPCRs (12%), transporter proteins (4%), and nuclear receptors (3.7%), highlighting a focus on chronic and life-threatening diseases, especially orphan disease indications. We compare regular and expedited review pathways across different therapeutic areas and observe that FDA expedited review programs have significantly increased access (67%) to new therapeutics, notably in oncology, where 80% to 100% of drugs utilize at least one expedited pathway. More than 70% of expedited approvals involved multiple pathways. Priority review emerged as the most common approval type, while accelerated approval was the least frequent. These findings illustrate ongoing trends in first-in-class drugs, the factors that drive drug innovation, and expedited approval processes. They also emphasize the importance of regulatory mechanisms in expediting the delivery of new treatments to patients. In our study, we examine the trends in drug approvals for non-communicable diseases, including cardiovascular diseases (8.6%), cancer (29%), respiratory illnesses (4.3%), and diabetes (3%), along with their pharmacological properties.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"277 ","pages":"Article 108945"},"PeriodicalIF":12.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427544","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

Drug discovery through biophysical techniques: Methods and applications 通过生物物理技术发现药物：方法和应用

IF 12.5 1区医学

Pharmacology & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-11-06 DOI: 10.1016/j.pharmthera.2025.108947

Yinhao Zhou, Haiyun Hu, Qiuyan Huang, Yuwei Tang, Yanli Liu

{"title":"Drug discovery through biophysical techniques: Methods and applications","authors":"Yinhao Zhou, Haiyun Hu, Qiuyan Huang, Yuwei Tang, Yanli Liu","doi":"10.1016/j.pharmthera.2025.108947","DOIUrl":"10.1016/j.pharmthera.2025.108947","url":null,"abstract":"<div><div>The rapid advancements in drug discovery have underscored the critical demand for sophisticated analytical methodologies capable of delivering comprehensive insights into molecular interactions, thereby accelerating the development of innovative therapeutic agents. As modern drug discovery increasingly depends on precise characterization of molecular dynamics and protein behavior, biophysical techniques have emerged as indispensable tools in pharmaceutical development. These techniques provide robust platforms for investigating protein–ligand interactions, elucidating structural basis, and deciphering cellular mechanisms—all essential components of rational drug design. In this review, we systematically summarize pivotal biophysical technologies shaping contemporary drug discovery, including Förster resonance energy transfer (FRET), fluorescence polarization (FP), thermal shift assays (TSA/CETSA), surface plasmon resonance (SPR), bio-layer interferometry (BLI), microscale thermophoresis (MST), isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR), X-ray crystallography, and advanced mass spectrometry (MS)-based approaches such as hydrogen–deuterium exchange mass spectrometry (HDX-MS) and crosslinking mass spectrometry (XL-MS). For each technique, we trace its historical development, outline fundamental principles, and highlight key innovations that have cemented its role in drug research. We also objectively evaluate the strengths and limitations of each method and discuss emerging trends, including improvements in sensitivity, automation, and high-throughput implementation. These developments promise to maintain their pivotal role in advancing biomedical research and therapeutic innovation, particularly in addressing the growing complexity of drug targets and the urgent need for precision medicine solutions.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"277 ","pages":"Article 108947"},"PeriodicalIF":12.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461309","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

Molecular, metabolic, and histological subtypes of pancreatic ductal adenocarcinoma and its tumor microenvironment: Insights into tumor heterogeneity and clinical implications 胰腺导管腺癌的分子、代谢和组织学亚型及其肿瘤微环境：对肿瘤异质性和临床意义的见解

IF 12.5 1区医学

Pharmacology & Therapeutics Pub Date : 2026-01-01 Epub Date: 2025-11-01 DOI: 10.1016/j.pharmthera.2025.108946

Yuuki Ohara , Huaitian Liu , Paloma Moreno , Seiya Suzuki , S. Perwez Hussain

{"title":"Molecular, metabolic, and histological subtypes of pancreatic ductal adenocarcinoma and its tumor microenvironment: Insights into tumor heterogeneity and clinical implications","authors":"Yuuki Ohara , Huaitian Liu , Paloma Moreno , Seiya Suzuki , S. Perwez Hussain","doi":"10.1016/j.pharmthera.2025.108946","DOIUrl":"10.1016/j.pharmthera.2025.108946","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous cancer with poor prognosis and limited therapeutic options. Bulk transcriptomic profiling has identified two major gene expression–based molecular subtypes: classical/progenitor and basal-like/squamous/quasimesenchymal. These subtypes differ in biological characteristics, differentiation status, drug sensitivity, and clinical outcomes. Advances in single-cell and spatial transcriptomics have further revealed intermediate/hybrid states, as well as distinct subtypes within the tumor microenvironment. These technologies have also uncovered intratumoral heterogeneity, tumor–stroma interactions, and spatially organized transcriptional programs that further shape subtype identity and plasticity, which can shift over time or under therapeutic pressure. In parallel, metabolomic analyses have revealed distinct metabolic subtypes that align with molecular subtypes and highlight subtype-specific metabolic rewiring and vulnerabilities. Furthermore, recent deep learning approaches applied to histopathology allow for high-resolution, morphology-based subtype prediction using Hematoxylin & Eosin-stained slides, providing practical and potentially scalable diagnostic tools. These multi-layered insights are reshaping PDAC taxonomy and enhancing our understanding of how transcriptional, metabolic, and spatial features together define tumor behavior and therapeutic response. This review discusses molecular (transcriptomic), metabolic, and histological subtyping approaches for PDAC, with the aim of enabling practical, cost-effective diagnosis and personalized medicine. By integrating data from recent experimental and clinical studies, we aim to provide a comprehensive and accessible overview of PDAC subtype heterogeneity, which may help guide future subtype-informed therapeutic strategies.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"277 ","pages":"Article 108946"},"PeriodicalIF":12.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423931","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

Treatment strategies for leptomeningeal disease in patients with breast cancer 乳腺癌患者轻脑膜疾病的治疗策略。

IF 12.5 1区医学

Pharmacology & Therapeutics Pub Date : 2025-12-01 Epub Date: 2025-10-08 DOI: 10.1016/j.pharmthera.2025.108933

Lennard Spanehl , Thomas Grinda , Rishab Ramapriyan , Himanshu Soni , Sarah Blitz , Philip Heesen , Rohan Jha , Chibueze D. Nwagwu , Florian A. Gessler , Pablo Valdes , Sarah L. Sammons , Wenya Linda Bi , Gregory K. Friedman , Ayal A. Aizer , E. Antonio Chiocca , Nancy U. Lin , Joshua D. Bernstock

{"title":"Treatment strategies for leptomeningeal disease in patients with breast cancer","authors":"Lennard Spanehl , Thomas Grinda , Rishab Ramapriyan , Himanshu Soni , Sarah Blitz , Philip Heesen , Rohan Jha , Chibueze D. Nwagwu , Florian A. Gessler , Pablo Valdes , Sarah L. Sammons , Wenya Linda Bi , Gregory K. Friedman , Ayal A. Aizer , E. Antonio Chiocca , Nancy U. Lin , Joshua D. Bernstock","doi":"10.1016/j.pharmthera.2025.108933","DOIUrl":"10.1016/j.pharmthera.2025.108933","url":null,"abstract":"<div><div>Leptomeningeal disease (LMD) associated with breast cancer (BC), characterized by the invasion of metastatic BC cells into the leptomeninges and cerebrospinal fluid, poses a significant clinical challenge. Current management strategies are not curative but rather aim to slow the rapid clinical decline associated with LMD, each with its own set of limitations. For instance, systemic chemotherapy faces delivery barriers while intrathecal administration directly targets the site of disease but struggles with uneven drug distribution, toxicity, and limited efficacy. Radiation therapy, including whole brain radiation, stereotactic radiosurgery, and proton craniospinal irradiation, offers palliative relief, though with varying levels of toxicity. The prognosis for patients with BC-associated LMD remains poor under existing treatment paradigms, highlighting an urgent need for innovative therapeutic strategies and delivery systems. Emerging approaches under investigation include advanced radiation techniques, targeted therapies, and novel immunotherapeutic modalities such as oncolytic viruses. Herein, we examine (1) contemporary treatment approaches for LMD in BC and (2) promising novel therapies that may reshape the management of this devastating condition.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"276 ","pages":"Article 108933"},"PeriodicalIF":12.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261160","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