Expert Review of Clinical Pharmacology最新文献_第6页

Potential beneficial effect of treatment with PCSK9 inhibitors on vascular endothelial dysfunction: a systematic review and meta-analysis. PCSK9抑制剂治疗血管内皮功能障碍的潜在有益效果：系统回顾和荟萃分析。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2026-05-01 Epub Date: 2026-05-06 DOI: 10.1080/17512433.2026.2667341

Christina Antza, Panagiota Anyfanti, Charalampia Savva, Konstantinos Malandris, Andrej Belančić, Yusuf Ziya Şener, Evangelia Chaida, Dimitrios Poulis, Vasilios Kotsis

{"title":"Potential beneficial effect of treatment with PCSK9 inhibitors on vascular endothelial dysfunction: a systematic review and meta-analysis.","authors":"Christina Antza, Panagiota Anyfanti, Charalampia Savva, Konstantinos Malandris, Andrej Belančić, Yusuf Ziya Şener, Evangelia Chaida, Dimitrios Poulis, Vasilios Kotsis","doi":"10.1080/17512433.2026.2667341","DOIUrl":"10.1080/17512433.2026.2667341","url":null,"abstract":"Introduction: PCSK9 inhibitors (PCSK9i) are at the center of research for their pleiotropic effects. The aim of this study is to systematically review the literature for their effect on vascular endothelial dysfunction.Methods: We systematically researched Embase, Ovid MEDLINE and CENTRAL for this purpose. Eligible studies were those assessing endothelial function by available noninvasive vascular methods. Meta-analysis was performed to compare differences on endothelial dysfunction between PCSK9i and placebo. Qualitative analysis was used for observational studies evaluating the outcome before and after PCSK9i.Results: We found 8 articles eligible, with the main outcome, among others, to be changes on flow-mediated dilation (FMD). Observational studies report an increase on FMD after PCSK9i treatment. Only 5 studies (415 participants) were eligible for the meta-analysis. Compared to placebo, PCSK9i increased FMD but not statistically significant (MD:0.84, 95%CI:-0.07,1.74). Alirocumab was associated with no difference in two studies (MD:-0.20, 95%CI:-0.73,0.34), whereas evolocumab with a statistically significant increase in FMD in four studies (MD:1.31, 95%CI:0.22,2.4).Conclusion: This is the first effort to summarize evidence on the effect of PCSK9i on endothelial function. PCSK9i may improve FMD, suggesting additional therapeutic roles beyond the traditional ones. Further, high-quality, large population studies are needed to confirm these findings.Protocol registration: The protocol utilized for this research is available in the Open Science Framework (OSF) database (https://osf.io/hz4d2/).","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"491-498"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 pharmacological profile of pacritinib for the treatment of myelofibrosis. 帕西替尼治疗骨髓纤维化的药理学概况。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2026-05-01 Epub Date: 2026-04-16 DOI: 10.1080/17512433.2026.2657856

Hannah Goulart, Lucia Masarova, Naveen Pemmaraju, Prithviraj Bose

{"title":"A pharmacological profile of pacritinib for the treatment of myelofibrosis.","authors":"Hannah Goulart, Lucia Masarova, Naveen Pemmaraju, Prithviraj Bose","doi":"10.1080/17512433.2026.2657856","DOIUrl":"10.1080/17512433.2026.2657856","url":null,"abstract":"Introduction: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, progressive cytopenias, and limited overall survival. While Janus kinase (JAK) inhibitors have transformed symptom- and spleen-directed management, many patients, particularly those with baseline thrombocytopenia, historically had limited therapeutic options due to treatment-related myelosuppression and exclusion from pivotal trials. Pacritinib was developed to address this unmet need through selective JAK2, ACVR1, and IRAK1 inhibition with relative sparing of JAK1.Areas covered: This review summarizes the pharmacologic properties, preclinical rationale, and clinical development of pacritinib for the treatment of MF. We discuss early-phase studies, pivotal phase III trials, dose-optimization efforts, and post-approval real-world data, with particular emphasis on patients with severe thrombocytopenia.Expert opinion: Pacritinib occupies a distinct niche within the MF treatment landscape, offering meaningful spleen and symptom benefit in patients with severe thrombocytopenia who historically lacked effective therapeutic options. While no JAK inhibitor has demonstrated clear disease-modifying effects in MF, pacritinib's non-myelosuppressive profile, unique activity against IRAK1, and potential anemia benefit via ACVR1 inhibition suggests potential utility as a backbone for future combination strategies. Ongoing and future studies will be critical to further define its role in phenotype-driven MF management.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"409-418"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Osteoarthritis and dementia: contrasting disorders driven by mutual pathways of autophagy, mTOR, GLP-1, AMPK, Wnt, and WISP1. 骨关节炎和痴呆：由自噬、mTOR、GLP-1、AMPK、wnt和WISP1相互通路驱动的对比疾病。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2026-05-01 Epub Date: 2026-05-11 DOI: 10.1080/17512433.2026.2671269

Kenneth Maiese

{"title":"Osteoarthritis and dementia: contrasting disorders driven by mutual pathways of autophagy, mTOR, GLP-1, AMPK, Wnt, and WISP1.","authors":"Kenneth Maiese","doi":"10.1080/17512433.2026.2671269","DOIUrl":"10.1080/17512433.2026.2671269","url":null,"abstract":"Introduction: Increased global lifespan is paralleled by a rise in non-communicable diseases with osteoarthritis and dementia, including Alzheimer's disease, impacting all nations with severe disability, death, and financial burden.Areas covered: Given that osteoarthritis and dementia are worsened with advancing age, progressive in nature, and presently remain only with symptomatic treatments, development of advanced comprehensive therapies is critical for these disorders. New innovative work offers insight into the underlying clinical bond between degenerative joint disease and cognitive loss. Data sources using systematic literature search employed PubMed, Scopus, Web of Science, and ScienceDirect from January 2021 through February 2026.Expert opinion: Although affecting diverse organ systems, degenerative joint disease and dementia are intimately connected by shared cellular pathways responsible for disease onset and progression. Pioneering avenues of investigation of oxidative stress, autophagy, the mechanistic target of rapamycin (mTOR), cellular metabolism mechanisms with glucagon-like peptide-1 (GLP-1) receptors and AMP activated protein kinase (AMPK), Wnt signaling, and Wnt1 inducible signaling pathway protein 1 (WISP1) offer exciting treatment opportunities for osteoarthritis and Alzheimer's disease. Ultimately, these complex pathways will necessitate focus upon their intricate dependence that may benefit from several targeted approaches including artificial intelligence applications for fruitful clinical translation.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"471-490"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Predictive and prognostic factors for immunotherapy response in head and neck squamous cell carcinoma: a narrative review. 头颈部鳞状细胞癌免疫治疗反应的预测和预后因素：叙述性回顾。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2026-05-01 Epub Date: 2026-04-28 DOI: 10.1080/17512433.2026.2665455

Concetta Calabrò, Giuseppe De Palma, Tarik Gheit, Serena Iacovelli, Giovanni Mastrandrea, Alessandro Rizzo, Loredana Palermo

{"title":"Predictive and prognostic factors for immunotherapy response in head and neck squamous cell carcinoma: a narrative review.","authors":"Concetta Calabrò, Giuseppe De Palma, Tarik Gheit, Serena Iacovelli, Giovanni Mastrandrea, Alessandro Rizzo, Loredana Palermo","doi":"10.1080/17512433.2026.2665455","DOIUrl":"10.1080/17512433.2026.2665455","url":null,"abstract":"Introduction: Immune checkpoint inhibitors (ICIs) have reshaped the therapeutic landscape of head and neck squamous cell carcinoma (HNSCC). However, only a subset of patients derives durable benefit, highlighting the need for reliable predictive factors of response.Areas covered: A literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science (2015-2026) using relevant keywords. This narrative review summarizes and categorizes currently available evidence on biological, inflammatory and clinical biomarkers associated with response to immunotherapy in HNSCC, with particular attention to PD-L1 expression, HPV status, tumor mutational burden, immune microenvironment, systemic inflammatory indices and performance status.Expert opinion: PD-L1 expression assessed by Combined Positive Score (CPS) remains the only validated clinical biomarker, although its dynamic and heterogeneous nature limits accuracy. HPV positivity, high tumor mutational burden, favorable immune microenvironment, low neutrophil-to-lymphocyte ratio and good Eastern Cooperative Oncology Group Performance Status (ECOG PS) are consistently associated with improved outcomes. No single marker adequately predicts. Response to immunotherapy in HNSCC is multifactorial. Integrating biological and clinical parameters may support a personalized approach to immunotherapy.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"419-428"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Developing treatment strategies to optimize outcomes in patients with psoriatic arthritis. 制定治疗策略以优化银屑病关节炎患者的预后。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2026-05-01 Epub Date: 2026-05-03 DOI: 10.1080/17512433.2026.2667340

Fadi Kharouf, Aiman Arraf, Vinod Chandran

{"title":"Developing treatment strategies to optimize outcomes in patients with psoriatic arthritis.","authors":"Fadi Kharouf, Aiman Arraf, Vinod Chandran","doi":"10.1080/17512433.2026.2667340","DOIUrl":"10.1080/17512433.2026.2667340","url":null,"abstract":"Introduction: Achieving sustained remission in psoriatic arthritis (PsA) remains challenging despite the availability of multiple biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Heterogeneous disease expression, comorbidities, and variable durability of response limit treatment effectiveness.Areas covered: This review summarizes contemporary and emerging pharmacologic approaches to PsA, spanning established therapies targeting tumor necrosis factor (TNF), the interleukin-23/interleukin-17 (IL-23/IL-17) axis, and Janus kinase (JAK) signaling, as well as emerging strategies such as selective tyrosine kinase 2 (TYK2) inhibition, dual JAK1/TYK2 inhibition, oral interleukin-23 receptor-targeted peptides, and novel biologic platforms. A structured literature search of PubMed, MEDLINE, and ClinicalTrials.gov was conducted for studies published between January 2000 and April 2026. Evidence from randomized controlled trials, long-term extension studies, and real-world observational cohorts informed assessment of efficacy, durability, safety, treatment sequencing, and drug survival, with emphasis on multidomain involvement and metabolic and non-inflammatory drivers of disease activity.Expert opinion: Progress in PsA management will depend less on expanding therapeutic options and more on improving sustained remission rates. Phenotype- and mechanism-informed treatment selection, proactive treat-to-target implementation, and systematic reassessment of residual inflammatory versus non-inflammatory disease activity are central to optimizing long-term outcomes. Emerging therapies may refine existing strategies by improving durability and safety.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"457-470"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Retatrutide in type 2 diabetes mellitus and obesity: an overview. 利特鲁肽治疗2型糖尿病和肥胖症的综述。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2026-04-01 Epub Date: 2026-03-10 DOI: 10.1080/17512433.2026.2642415

Theodoros Panou, Evanthia Gouveri, Djordje S Popovic, Nikolaos Papanas

{"title":"Retatrutide in type 2 diabetes mellitus and obesity: an overview.","authors":"Theodoros Panou, Evanthia Gouveri, Djordje S Popovic, Nikolaos Papanas","doi":"10.1080/17512433.2026.2642415","DOIUrl":"10.1080/17512433.2026.2642415","url":null,"abstract":"Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for T2DM and obesity.Areas covered: An electronic search was conducted in Scopus, PubMed/MEDLINE, and Google Scholar databases. Retatrutide (LY3437943) is a novel triple agonist targeting glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1 R). In subjects with type 2 diabetes mellitus (T2DM), decreased glycated hemoglobin (HbA1c) by up to 2.16% and decreased fasting glucose by up to 69.1 mg/dL have been seen. Weight loss up to 16.94% was observed in subjects with T2DM. Subjects with overweight or obesity experienced a greater weight loss by up to 26.56% (24.15 kg). Reductions in body-mass index and waist circumference were achieved. In subjects with T2DM and overweight or obesity, decreased systolic blood pressure was found. Finally, relative liver fat count in subjects with metabolic dysfunction-associated steatotic liver disease (MASLD) was reduced by up to 86%. Increased frequency of mild-to-moderate gastrointestinal adverse events (mainly nausea, vomiting, constipation, and diarrhea) was reported in participants on the highest retatrutide doses, likely due to rapid dose escalation and higher starting dose.Expert opinion: These promising effects on glycemic control, weight loss, and emerging pleiotropic actions merit further investigation.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"313-339"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Osteoarthritis and cardiometabolic diseases: shared mechanisms, modifiable risk factors, and integrated management strategies. 骨关节炎和心脏代谢疾病：共同机制、可改变的危险因素和综合管理策略

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2026-04-01 Epub Date: 2026-03-24 DOI: 10.1080/17512433.2026.2649611

Patricia Yl Chan, Shiwen Yuan, David J Hunter

{"title":"Osteoarthritis and cardiometabolic diseases: shared mechanisms, modifiable risk factors, and integrated management strategies.","authors":"Patricia Yl Chan, Shiwen Yuan, David J Hunter","doi":"10.1080/17512433.2026.2649611","DOIUrl":"10.1080/17512433.2026.2649611","url":null,"abstract":"Introduction: Osteoarthritis (OA) and cardiometabolic diseases (CMD), including metabolic syndrome, type 2 diabetes, and cardiovascular disease, are common chronic disorders sharing risk factors, mechanisms, and societal burdens. Obesity, insulin resistance, dyslipidaemia, hypertension, and inflammation link joint damage with vascular and metabolic issues. Factors such as advanced glycation end-products, adipokines, and cytokines including interleukin-6 and C-reactive protein drive systemic and local inflammation, accelerating joint deterioration and cardiovascular problems.Areas covered: We searched MEDLINE, PubMed, Embase, Cochrane, Scopus, CIAP, and Google Scholar from January 2011 to October 2025. Evidence supports a bidirectional relationship where OA worsens cardiometabolic risk via inactivity, and CMD accelerates OA through vascular and metabolic stress. Without disease-modifying drugs, lifestyle interventions like weight management and physical activity are key. Multidisciplinary care targeting shared modifiable risk factors can improve outcomes.Expert opinion: Future research should investigate shared molecular pathways using approaches like multi-omics, validate early-detection biomarkers, and assess multimodal interventions that link musculoskeletal and metabolic health. A patient-centered approach to OA and CMD offers the best chance to reduce disability and disease burden.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"341-355"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Pharmacokinetics, efficacy, and safety of arsenic formulations in acute promyelocytic leukemia treatment. 砷制剂治疗急性早幼粒细胞白血病的药代动力学、疗效和安全性。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2026-04-01 DOI: 10.1080/17512433.2026.2652979

Jennifer Marvin-Peek, Wei-Ying Jen, Farhad Ravandi

{"title":"Pharmacokinetics, efficacy, and safety of arsenic formulations in acute promyelocytic leukemia treatment.","authors":"Jennifer Marvin-Peek, Wei-Ying Jen, Farhad Ravandi","doi":"10.1080/17512433.2026.2652979","DOIUrl":"10.1080/17512433.2026.2652979","url":null,"abstract":"Introduction: Acute promyelocytic leukemia (APL) is a highly curable subtype of AML, largely due to the introduction of differentiating therapy with all-trans retinoic acid and arsenic trioxide. While intravenous arsenic trioxide (ATO) is considered the standard-of-care in the United States, its prolonged administration and monitoring requirements pose logistical challenges that require high healthcare resource utilization and negatively impact quality of life.Areas covered: This review summarizes the development and clinical evaluation of intravenous and oral arsenic formulations in APL. We discuss the pharmacokinetics, safety, and efficacy of oral arsenic compared with intravenous ATO across populations, including children and patients with obesity or renal impairment. A PubMed search using the terms 'oral arsenic,' 'arsenic trioxide,' 'arsenic formulations,' 'acute promyelocytic leukemia,' and 'pharmacokinetics' was used to compile data. It draws on current pharmacokinetic and clinical evidence, including data from retrospective publications, phase 3 trials, meta-analyses, and long-term follow-up studies.Expert option: Oral arsenic formulations achieve comparable molecular remission, long-term survival, and toxicity profiles to intravenous ATO. These oral formulations may offer meaningful advantages in quality of life, cost, and overall availability of optimal treatment. Continued clinical trials are expected to further define oral arsenic's role in frontline therapy in the United States.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"369-382"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

PD-1/PD-L1 for prostate cancer: from clinical trials to practice. PD-1/PD-L1治疗前列腺癌：从临床试验到实践

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2026-04-01 Epub Date: 2026-03-31 DOI: 10.1080/17512433.2026.2649610

Aaron Holmes, Tobechukwu Okobi, Abdul Baseet Arham, Neil Vaishampayan, Deepthi Subramanya, Scott T Tagawa

{"title":"PD-1/PD-L1 for prostate cancer: from clinical trials to practice.","authors":"Aaron Holmes, Tobechukwu Okobi, Abdul Baseet Arham, Neil Vaishampayan, Deepthi Subramanya, Scott T Tagawa","doi":"10.1080/17512433.2026.2649610","DOIUrl":"10.1080/17512433.2026.2649610","url":null,"abstract":"Introduction: A growing number of malignancies have shown favorable responses to immune checkpoint inhibitors (ICI), most commonly anti-PD-(L)1 antibodies. However, prostate cancer has been associated with mostly unfavorable responses to ICI. This review discusses various trials related to PD-(L)1 inhibitors in prostate cancer.Areas covered: We wrote a review article based upon content and practice expertise supplemented with review of the literature. The focus was on PD-1 or PD-L1 inhibitors in prostate cancer.Expert opinion: Clinical trials with PD-(L)1 inhibitors in patients with prostate cancer administered alone or in combination with other therapies do not appear to have significant benefit in unselected patients, whether part of initial systemic therapy or after the development of hormone resistance. However, there may be benefits in selected tumors harboring mutations with microsatellite instability high/mismatch repair deficiency (MSI-H/dMMR) and, to a lesser extent, high tumor mutational burden (TMB-H). While only a small percentage of prostate tumors have these mutations (MSI-H/dMMR: 3%) and (TMB-H: 4.5%), panel genomic testing can help identify subsets of patient populations who may benefit from PD-(L)1 inhibitors in addition to other molecularly selected agents.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"357-367"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 tiered decisional framework for genetic epileptic syndromes with or without encephalopathies: from standard care to investigational strategies. 有或无脑病的遗传性癫痫综合征的分层决策框架：从标准治疗到研究策略。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2026-04-01 Epub Date: 2026-03-31 DOI: 10.1080/17512433.2026.2652967

Lorenzo Perilli, Alessandro Ferretti, Antonella Riva, Salvatore Grosso, Alberto Verrotti, Pasquale Striano

{"title":"A tiered decisional framework for genetic epileptic syndromes with or without encephalopathies: from standard care to investigational strategies.","authors":"Lorenzo Perilli, Alessandro Ferretti, Antonella Riva, Salvatore Grosso, Alberto Verrotti, Pasquale Striano","doi":"10.1080/17512433.2026.2652967","DOIUrl":"10.1080/17512433.2026.2652967","url":null,"abstract":"Introduction: Developmental and epileptic encephalopathies (DEEs), epilepsy-associated neurodevelopmental disorders (NDD), and epileptic syndromes with or without encephalopathy (ES±E) share overlapping genetic architectures where both etiology and seizures impair development. Despite genomic advances, many patients remain pharmacoresistant, and molecular diagnoses seldom translate into targeted treatments. This review connects mechanistic categories to precision therapies, providing a clinical decision-making framework.Area covered: We outline pharmacological and investigational strategies-including antiseizure medications, dietary therapies, and disease-modifying approaches-across major mechanistic categories, including ion channel/receptor dysfunctions, synaptic/signaling defects, metabolic disorders, and neurodegenerative storage diseases. For each condition, potential therapeutic options are interpreted within a hierarchical precision-based framework, ranging from empiric seizure-type-driven treatments to gene-specific molecular interventions. A narrative literature search was conducted across major databases for English-language articles on DEEs, NDD, ES±E, and precision therapeutic approaches published up to early 2026. We categorized potential therapeutic interventions into five hierarchical tiers based on etiological specificity and evidence. Classification, achieved by expert consensus, distinguishes established (Tiers 1-3) from emerging strategies (Tiers 4-5).Expert opinion: Progress depends on early etiological diagnosis and timely, mechanism-informed therapy. Future advances require expanded genomic testing, natural history studies, mechanism-based biomarkers, and innovative trial designs tailored to complex pediatric populations.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"383-401"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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