Frontiers in Pharmacology最新文献

{"title":"The Rho/MRTF-pirin axis: a promising target for overcoming melanoma drug resistance.","authors":"Xiaoyan Chen, Junfeng Zhang, Bao Zhang, Zhi Li","doi":"10.3389/fphar.2025.1571933","DOIUrl":"https://doi.org/10.3389/fphar.2025.1571933","url":null,"abstract":"","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1571933"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic modifications of gut microbiota and their potential role in atherosclerosis.","authors":"Shuang Guo, Junlai Zhao, Rongrong Zhu, Zhi Fan, Shibiao Liu, Weiwei Wu","doi":"10.3389/fphar.2025.1638240","DOIUrl":"https://doi.org/10.3389/fphar.2025.1638240","url":null,"abstract":"<p><p>Emerging evidence positions the gut microbiota as a pivotal regulator of host metabolism and immunity, particularly in atherosclerosis pathogenesis, with epigenetic mechanisms serving as fundamental mediators of gene expression control. This review systematically summarizes gut microbiome-driven epigenetic pathways, encompassing DNA methylation, histone modifications, non-coding RNA networks and their interplay with atherosclerosis-related pathological processes. We synthesize current evidence on microbiota-epigenome crosstalk, highlighting its potential mechanistic contributions to atherosclerotic plaque development.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1638240"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological mechanisms and potential clinical applications of Dihydromyricetin in neurological disorders.","authors":"Yike Zhang, Tingting Zhang, Manli Zhao, Peichun Li, Tao Liu, Jiangbo Xie","doi":"10.3389/fphar.2025.1618623","DOIUrl":"https://doi.org/10.3389/fphar.2025.1618623","url":null,"abstract":"<p><p>Neurological disorders (e.g., Alzheimer's disease, Parkinson's disease, and stroke) have complex pathogenesis and affect a substantial proportion of the population; yet, available treatments have poor or limited efficacy, and the patients have a poor prognosis, with high morbidity and mortality. Dihydromyricetin (DHM), a flavonoid compound extracted from plants, has received widespread attention in recent years because of its diverse pharmacological effects. <i>In vitro</i> and <i>in vivo</i> studies have revealed its substantial antioxidant, anti-inflammatory, and neuroprotective properties, making it a promising candidate for the treatment of central nervous system disorders through multiple mechanisms and pleiotropic effects. Therefore, there is an urgent need to develop novel therapeutic strategies. DHM is an attractive candidate for the management of neurological disorders, but there is a lack of a systematic summary of the knowledge status and gaps. Therefore, to address this challenge, we systematically reviewed the pharmacological mechanisms of DHM in central nervous system disorders and its potential applications in related conditions. We analyzed the therapeutic potential and current challenges of DHM to provide a reference for its development and application as a novel therapeutic agent. The review suggests that DHM possesses significant potential for the management of neurological disorders.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1618623"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Building trust in clinical research: a systems approach to ethical engagement and sustainable outcomes.","authors":"Johanna M C Blom, Veronica Rivi, Fabio Tascedda, Luca Pani","doi":"10.3389/fphar.2025.1570899","DOIUrl":"https://doi.org/10.3389/fphar.2025.1570899","url":null,"abstract":"<p><p>Trust and trustworthiness are critical to the success of clinical research, profoundly influencing participant engagement, data integrity, and study outcomes. These behaviors emerge from complex, dynamic interactions within the clinical research ecosystem, involving stakeholders such as sponsors, participants, clinicians, researchers, and regulatory bodies. The rapid development of COVID-19 vaccines has underscored the potential of scientific advancements to build public trust in the scientific outcomes, while also exposing vulnerabilities in the procedural trust framework due to misinformation and historical unethical practices. This paper explores trust and trustworthiness as emergent properties within the complex systems of clinical research, highlighting their evolution through transparent communication, participant empowerment, and ethical governance. A systems approach is emphasized, where trust develops holistically, influenced by regulatory frameworks, interpersonal relationships, and the overall research environment. Practical implications include the adoption of adaptive consent models, interdisciplinary collaboration, and the integration of continuous feedback mechanisms. To address trust erosion, especially among marginalized communities, we advocate for participatory research approaches and the development of new professional competencies, such as the role of a Clinical Research Liaison. This role would ensure ongoing alignment with community needs, enhance transparency, and maintain ethical standards, ultimately fostering a research environment where trust and trustworthiness thrive, benefiting both participants and the broader scientific community. A roadmap for future efforts includes the systematic incorporation of these elements into clinical research practices to enhance trust and improve research outcomes.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1570899"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of using pentoxifylline in patients undergoing breast cancer surgery.","authors":"Samar A Dewidar, Noha O Mansour, Omar Hamdy, Dina A Elebedy, Moetaza M Soliman, Mohamed E E Shams","doi":"10.3389/fphar.2025.1560805","DOIUrl":"https://doi.org/10.3389/fphar.2025.1560805","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer surgery presents several challenges, including postoperative pain, and wound healing complications. Pentoxifylline is a synthetic methylxanthine derivative known for its anti-inflammatory properties and ability to improve microcirculation, decreasing the inflammatory markers as well as restoring the antioxidant status. This study aims to investigate the potential benefits of pentoxifylline in improving pain control and wound healing in patients undergoing mastectomy.</p><p><strong>Methods: </strong>In a randomized, single-blinded clinical trial, ninety-two breast cancer patients were assigned to receive pentoxifylline or not. The primary outcome was the measurement of postoperative pain level using the Numeric Rating Scale (NRS) at multiple time points within 24 h post-surgery. Secondary outcomes included determining the time till wound healing and the incidence of postoperative complications.</p><p><strong>Results: </strong>Eighty-eight participants completed this study, 42 patients in the control group while 46 patients in the pentoxifylline group. Patients receiving pentoxifylline demonstrated a significant decrease in NRS scores as compared to the control group (median (IQR) of total area under the curve (AUC) over 24 h were 90 (73.5-102), and 153 (123-168), respectively (<i>P</i> < 0.001)), indicating clinically meaningful reductions in pain intensity. Additionally, pentoxifylline-treated patients experienced faster wound healing, reflected by earlier suture removal (mean ± SD: 15 ± 4.4 days vs. 19.3 ± 6.7 days; respectively (<i>P</i>= 0.001)). The incidence of postoperative complications was significantly lower in the pentoxifylline group (2.2%) compared the control group (19%)<i>, P= 0.01</i>. Fewer cases of seroma, wound infection, and wound dehiscence were observed in the pentoxifylline group.</p><p><strong>Conclusion: </strong>Preoperative oral administration of pentoxifylline in patients undergoing breast surgery may reduce postoperative pain and improve recovery in those patients. However, further investigations are imperative to validate these findings.</p><p><strong>Clinical trial registration: </strong>https://clinicaltrials.gov/study/NCT06087237, identifier NCT06087237.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1560805"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymorphisms in <i>CYP3A5, CYP3A4</i>, and <i>ABCB1</i> genes: implications for calcineurin inhibitors therapy in hematopoietic cell transplantation recipients-a systematic review.","authors":"Luiz Carlos da Costa-Junior, Daniely Regina Freitas-Alves, Amanda Melo Leite Leão, Hayra de Andrade Vieira Monteiro, Rita de Cássia Barbosa da Silva Tavares, Maria Claudia Rodrigues Moreira, Marília Berlofa Visacri, Teresa de Souza Fernandez, Paulo Caleb Júnior de Lima Santos","doi":"10.3389/fphar.2025.1569353","DOIUrl":"https://doi.org/10.3389/fphar.2025.1569353","url":null,"abstract":"<p><p>This systematic review assessed the impact of <i>CYP3A5</i>, <i>CYP3A4</i>, and <i>ABCB1</i> polymorphisms on the pharmacokinetics and clinical outcomes of calcineurin inhibitors in hematopoietic cell transplantation (HCT) recipients. Following PRISMA 2020 guidelines, the protocol was registered in PROSPERO (CRD42024517094). A comprehensive search in PubMed, BVS, Scopus, Web of Science, Embase, and Cochrane databases (2013-2024) identified observational studies focusing on tacrolimus or cyclosporine and the specified polymorphisms. Studies on non-human subjects, solid organ transplants, pharmacokinetic models, and drug interactions were excluded. Narrative synthesis was employed due to heterogeneity, and study quality was evaluated using the Newcastle-Ottawa Scale (NOS) and STREGA guidelines. Of 301 records, 11 studies met inclusion criteria, predominantly retrospective and involving adult populations, with sample sizes ranging from 20 to 420 HCT recipients from the USA, Japan, and France. Outcomes included drug levels, median concentration/dose (C/D) ratio, therapeutic index, and clinical endpoints such as graft-versus-host disease (GVHD) and acute kidney injury (AKI). <i>CYP3A5*3</i> (rs776746) significantly influenced tacrolimus levels, C/D ratio, and clinical outcomes, highlighting its potential as a pharmacogenetic biomarker. <i>CYP3A4</i> and <i>ABCB1</i> polymorphisms demonstrated limited effects on tacrolimus pharmacokinetics and no significant clinical impact. Methodological quality was high, with 55% of studies achieving the maximum NOS score, although gaps in error rates and population modeling were noted. Limitations include variability in outcomes precluding meta-analysis, a small number of studies, particularly on cyclosporine, and insufficient data on <i>CYP3A4</i> and <i>ABCB1</i>. Further research is necessary to validate findings.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD42024517094, PROSPERO, CRD42024599998.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1569353"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing the potential targets and mechanisms of liver damage induced by acetyl tributyl citrate plasticizer using network toxicology, molecular docking and <i>in vitro</i> experiments.","authors":"Dong-Qun Guo, Yu-Ming Fang, Zhen-Dong Sun, Ya-Fen Zeng, Gui-Dan Wang, Jin-Wei Liang","doi":"10.3389/fphar.2025.1636576","DOIUrl":"https://doi.org/10.3389/fphar.2025.1636576","url":null,"abstract":"<p><strong>Background: </strong>Acetyl tributyl citrate (ATBC) may have adverse effects on liver health; however, the underlying mechanisms and pathophysiology remain unclear. The objective of this study was to elucidate the complex effects of ATBC on the liver and to determine the underlying molecular mechanisms by which environmental pollutants affect the disease process.</p><p><strong>Methods: </strong>We used network toxicology and molecular docking techniques to analyze potential targets and mechanisms of liver injury caused by ATBC plasticizer. Potential targets associated with ATBC exposure and liver injury were identified by using ChEMBL, STITCH, GeneCards and OMIM databases. Enrichment analysis was performed using the DAVID database (https://david.ncifcrf.gov/) to identify biological pathways associated with these genes. Finally, transcription quantitative polymerase chain reaction, CCK-8 assay, Western blot, and immunofluorescence staining were used to assess the effect of candidate potential targets on liver injury.</p><p><strong>Results: </strong>A total of 74 common targets associated with ATBC and liver injury were obtained. Enrichment analysis emphasized the association between these plastocyanin-targeted genes and the apoptotic pathway, suggesting that plastocyanin has a broad impact on cell survival. Moreover, molecular docking analysis demonstrated that ATBC exhibited a specific binding affinity for TNF-α, thereby suggesting that TNF-α plays a pivotal role in the regulation of liver damage pathogenesis. <i>In vitro</i> experiments further validated the expression of this molecule with the apoptosis marker molecules BAX and Bcl2 in ATBC-induced liver injury.</p><p><strong>Conclusion: </strong>The study suggests that TNF-α is involved in the process of ATBC-induced liver damage and may be related to cell apoptosis.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1636576"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pakistan's first medicine price deregulation policy: assessing its impact on prices, affordability, and availability of oral anti-diabetic medicines in private pharmacies.","authors":"Amna Saeed, Sundus Shukar, Najwa Ali Yasin, Caijun Yang, Minghuan Jiang, Muhammad Majid Aziz, Haris Zahoor, Muhammad Sunnan-Ud-Din, Yu Fang, Zaheer-Ud-Din Babar","doi":"10.3389/fphar.2025.1627735","DOIUrl":"https://doi.org/10.3389/fphar.2025.1627735","url":null,"abstract":"<p><strong>Introduction: </strong>Pakistan's highest diabetes prevalence necessitates equitable access to anti-diabetic medicines. This study evaluated the access to Oral antidiabetics (OADs) and the effect of Pakistan's recently launched price deregulation policy-applicable to medicines not included on the National Essential Medicines List (non-NEML)-on their prices and affordability by comparing NEML and non-NEML OADs.</p><p><strong>Methods: </strong>A WHO/HAI methodology-based survey in 30 private pharmacies across six regions gathered prices and availability data of 30 OADs, including the Lowest Price Generic (LPG), Highest Price Generic (HPG), and originator brand (OB). These selected OADs consisted of 11 products from NEML and 19 non-NEML products, comprising 17 single-active ingredient and 13 multi-active ingredient formulations. Published and surveyed retail prices of OADs (in Pakistani Rupees, PKR) before and after deregulation were compared, and the policy's effect was determined by difference-in-differences (DiD) analysis. Affordability for the lowest-paid employee and medicine availability in percentages were calculated.</p><p><strong>Results: </strong>The DiD analysis revealed that the unit prices of OADs were significantly increased by PKR 15.08 (OB), PKR 5.89 (HPG), and PKR 2.81 (LPG) (<i>p</i> < 0.05) within just 6 months of the policy's introduction. Medicines listed on the NEML remained consistently cheaper than non-NEML, with differences of -30.20 for OBs, -9.83 for HPGs, and -7.51 for LPGs in PKR (<i>p</i> < 0.001). As per DiD interaction terms (NEML enlistment status × deregulation), a greater increase in prices of non-NEML OBs was observed compared to NEML counterparts (PKR -10.85, <i>p</i> ≈ 0.05), while differences observed for LPGs (PKR 0.77, <i>p</i> = 0.73) and HPGs (PKR -0.20, <i>p</i> = 0.95) were insignificant. Prices of both single and multi-active ingredient formulations also increased significantly (<i>p</i> < 0.05). Although most OADs had fair availability from 47% to 97% after deregulation, seven out of 30 OADs remained unaffordable at both time points, and the overall affordability declined significantly post-deregulation (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>The study revealed significant price escalations for most OADs, particularly those not enlisted on NEML, highlighting access challenges for diabetic patients and necessitating targeted policy reforms that address key market-related factors to ensure equitable access to OADs.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1627735"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A scoping review about smoking, smoking cessation and their effects on anti-tuberculosis agents: insights into drug metabolisms, safety, and effectiveness.","authors":"Carlo Maria Bellanca, Simone Pietro Polosa, Egle Augello, Giulia Di Benedetto, Chiara Burgaletto, Anna Flavia Cantone, Gabriella Gaudio, Giuseppe Nunnari, Davide Campagna, Jennifer M Nailes, Hamza Shahbaz, Reza Kurniawan Tanuwihardja, Anant Mohan, Manuela Ceccarelli, Renato Bernardini, Andrea Marino, Giuseppina Cantarella","doi":"10.3389/fphar.2025.1606150","DOIUrl":"https://doi.org/10.3389/fphar.2025.1606150","url":null,"abstract":"<p><p>The World Health Organization (WHO) ranks tuberculosis (TB) as one of the top 10 causes of deaths worldwide. Notably, tobacco smoking represents a significant promoting factor in TB progression, being associated with poorer treatment outcomes, delayed conversion to negative smear or culture, and higher dropout rates from treatment plans. Remarkably, high rates of smoking and TB frequently overlaps in the same countries, warranting the need for targeted public health interventions. Prioritising smoking cessation is essential for smokers with TB, as sustained abstinence has been associated with reduced mortality and a more successful cure. This review examines the intricate relationship between cigarette smoking, smoking cessation therapies and anti-TB drugs, focusing on the impact of tobacco smoking compounds on liver detoxifying systems, such as influence of polycyclic aromatic hydrocarbons (PAHs) on hepatic cytochrome P450 (CYP450) enzymes mostly, and on metabolism of antituberculous medications. Integrating smoking cessation and TB treatment programmes must also take into account potential drug-drug interactions between smoking cessation medications and anti-TB drugs, a critical area for patient safety and effective TB management. This review article aims to provide healthcare professionals with the knowledge to better support TB patients who smoke or are intending to quit, to ensure tailored and effective treatment strategies, while highlighting gaps in current research and advocating for further studies to fill these gaps.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1606150"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and cost-effectiveness of pharmacogenomic testing for anthracycline-induced cardiotoxicity in childhood cancer: a systematic review and meta-analysis.","authors":"Ling Yin Fritz Wong, Alastair G Sutcliffe, Carmen Lok Tung Ho, Yan Lu, Carrie L Williams, Faiza Afzal, Mitana Purkayastha","doi":"10.3389/fphar.2025.1568320","DOIUrl":"https://doi.org/10.3389/fphar.2025.1568320","url":null,"abstract":"<p><strong>Background: </strong>Anthracyclines are widely used paediatric chemotherapy drugs, but anthracycline-induced cardiotoxicity (ACT) can cause heart failure in 16% of children. Previous studies have linked genetic variants to ACT and proposed pharmacogenomic testing for anthracycline-treated children; however, this approach remains unrealised. Therefore, this systematic review and meta-analysis evaluates the effectiveness of pharmacogenomic testing for ACT in childhood cancer.</p><p><strong>Methods: </strong>Nine bibliographic databases, three trial registers, reference lists and conference abstracts were searched from inception until October 2024. Two reviewers independently performed study selection, data extraction and quality assessment. Clinical effectiveness was defined as: 1) genetic associations, assessed using random-effects meta-analyses of odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) for variants examined in ≥2 studies; and 2) prediction accuracy, measured using area under the receiver operating characteristic curve (AUC) of pharmacogenomic models. Cost-effectiveness was assessed using incremental cost-effectiveness ratio (ICER).</p><p><strong>Results: </strong>Among 1,215 de-duplicated records, we included 37 clinical effectiveness studies (26,446 patients). Five cardiotoxic (<i>ABCC2</i> rs8187710, <i>ETFB</i> rs79338777, <i>GPR35</i> rs12468485, <i>HNMT</i> rs17583889 and <i>UGT1A6</i> rs17863783; pooled OR range 1.84-6.12; CI range 1.04-18.56) and two cardioprotective (<i>GSTA2</i> rs2180314 and <i>HFE</i> rs1799945; pooled OR range 0.62-0.63; CI range 0.46-0.84) variants were significantly associated with ACT. Another cardioprotective variant, <i>ABCC5</i> rs7627754, increased left ventricular ejection fraction (MD 7.39%; CI 4.63%-10.14%) and fractional shortening (MD 5.04%; CI 2.00%-8.08%). Pharmacogenomic models using clinical and genetic variables (AUC range 0.67-0.87) showed higher accuracy in predicting ACT than those using clinical variables (AUC range 0.57-0.81) across five studies. We identified only one cost-effectiveness study (100 patients), showing one of these models reduced costs (-5.7%) and mortality (-17%) compared to standard care (ICER-negative). Overall, the evidence was graded as very-low-certainty across all outcomes due to imprecision, inconsistency and publication bias.</p><p><strong>Conclusion: </strong>Despite promising results, this review highlights the lack of robust evidence to support pharmacogenomic testing for ACT in children. Further cost-effectiveness studies and ethnically diverse prediction models are needed to demonstrate the impact of pharmacogenomic testing on ACT prognosis and clinical decision-making prior to adoption.</p><p><strong>Systematic review registration: </strong>PROSPERO identifier CRD42024557946.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1568320"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}