Pharmacogenomics & Personalized Medicine最新文献

{"title":"Molecular Epidemiology of Thalassemia in University Town, Chongqing: Spectrum of Pathogenic Variants and Implications for Carrier Screening.","authors":"Wei Cai, Yi Liang, Li-Na Kang, Ya-Qian Jin, Pan Xu","doi":"10.2147/PGPM.S608098","DOIUrl":"10.2147/PGPM.S608098","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to characterize the molecular epidemiology of α-/β-thalassemia in Chongqing's University Town population in the University Town area of Chongqing, China.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 1012 individuals (comprising 840 females and 172 males, reflecting referral bias rather than biological sex differences) who underwent thalassemia genetic testing between June 2020 and February 2023. Genetic variants were detected using a combination of PCR and flow-through hybridization. Detection rates were compared between sexes using the chi-squared test. Hematological parameters were compared between carriers and a control group using the Mann-Whitney <i>U</i>-test.</p><p><strong>Results: </strong>The heterozygous carrier rates for α- and β-thalassemia were 12.1% and 11.4%, respectively. The overall detection rate was significantly higher in males (30.2%) than in females (22.1%). The predominant α-thalassemia variants were the -SEA deletion and the -3.7 kb deletion. The most frequent β-thalassemia variants were CD41-42, CD17, and IVS-II-654. Compared to controls, thalassemia carriers exhibited significantly elevated red blood cell (RBC) count and red cell distribution width (RDW), alongside reduced hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC).</p><p><strong>Conclusion: </strong>The spectrum of thalassemia gene variants in this Chongqing population exhibits distinct regional patterns. University Town hosts a young and highly mobile population with diverse regional origins, making it a representative area for epidemiological sampling. Furthermore, standard complete blood count (CBC) testing cannot reliably distinguish thalassemia from iron deficiency anemia. The findings underscore the necessity of widespread genetic screening among newborns, school-aged children, and individuals of reproductive age for early carrier identification. This is crucial for effective genetic counseling, reproductive risk assessment, and the prevention of severe thalassemia births in the region.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"19 ","pages":"608098"},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148610149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population-Based Assessment of Phenoconversion Potential in Switzerland: A Claims Data Study of Key Drug-Metabolizing Enzymes and Transporters.","authors":"Marietta M Roth, Aline Bencastro, Christoph R Meier, Carola A Huber, Henriette E Meyer Zu Schwabedissen, Samuel S Allemann, Cornelia Schneider","doi":"10.2147/PGPM.S586384","DOIUrl":"10.2147/PGPM.S586384","url":null,"abstract":"<p><strong>Purpose: </strong>Drug-drug-gene interactions can alter drug exposure and thereby increase the risk of clinically relevant outcomes, such as concentration-dependent toxicity (eg, tacrolimus toxicity in the context of altered CYP3A4/5 activity) or reduced treatment effectiveness. Despite their emerging relevance in clinical research, drug-drug-gene interactions remain understudied and are often ignored in clinical practice. Our objective was to assess the risk of phenoconversion by identifying potential drug-drug-gene interactions involving the transporters OATP1B1 and BCRP and the enzymes CYP2B6 and CYP3A4/5 in the Swiss population.</p><p><strong>Patients and methods: </strong>Using claims data from the Helsana basic health insurance, we identified all persons of all ages with at least one drug claim between 2017 and 2021 and with Helsana basic health insurance coverage for at least one full year. For the five-year analysis, only persons with insurance for the entire five-year period were included. Within this study population, we assessed and ranked the frequency of potential drug-drug-gene interactions of a pharmacogenetic substrate and an inhibitor/inducer of OATP1B1, BCRP, CYP2B6, or CYP3A4/5. Potential drug-drug-gene interactions were defined as the co-occurrence of a pharmacogenetic substrate and an inhibitor/inducer within a 30- or 5-days window.</p><p><strong>Results: </strong>During the entire five-year period, 18'523 (2.1%) and 12'645 (1.4%) individuals were exposed to potential drug-drug-gene interactions using the 30-day and 5-day windows, respectively. Potential drug-drug-gene interactions most frequently involved CYP3A4/5 (81.0% and 85.3%), followed by CYP2B6 (10.9% and 8.7%) and OATP1B1 (8.7% and 13.3%). The top three drug classes involved were nervous system drugs (75.1%), cardiovascular drugs (10.6%), and dermatologicals (4.0%). Quetiapine ranked first in the number of involved drug pairs, with quetiapine - metamizole being the predominant drug pair.</p><p><strong>Conclusion: </strong>In Switzerland, two out of 100 persons taking drugs metabolized or transported by OATP1B1, BCRP, CYP2B6, and CYP3A4/5 are at potential risk of phenoconversion, predominantly involving CYP3A4/5. These findings quantify real-world phenoconversion potential at the population level and underscore the need for outcome- and genotype-linked studies to determine clinical relevance. As this study was not designed to assess clinical outcomes, future genotype- and outcome-linked investigations are required to determine the actual impact on adverse drug reactions or treatment effectiveness.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"19 ","pages":"586384"},"PeriodicalIF":2.4,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148037722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Massive Hepatocellular Carcinoma with Insufficient Future Liver Remnant Achieved Complete Response After Two-Stage Hepatectomy Combined with Hepatic Arterial Infusion Chemotherapy and Lenvatinib-sintilimab: A Case Report.","authors":"Ruoxiang Xu, Mingrui Zhang, Zhiming Zeng, Yongguang Wei, Xiwen Liao, Chengkun Yang, Tao Peng, Hao Su","doi":"10.2147/PGPM.S578577","DOIUrl":"10.2147/PGPM.S578577","url":null,"abstract":"<p><p>Massive hepatocellular carcinoma (HCC) is not suitable for radical surgery due to the factors of high tumor burden and poor postoperative liver function tolerance. There are few reports on the conversion therapy for HCC with insufficient future liver remnant (FLR) volume using a combination of two - stage hepatectomy (TSH), hepatic arterial infusion chemotherapy (HAIC), and lenvatinib - sintilimab. We report a case of a 62-year-old male with massive HCC (81mm×11.5mm×95mm). At the initial diagnosis, the ratio of his FLR to standard liver volume (SLV) was 34%. After multidisciplinary team (MDT) discussion, the patient decided to undergo conversion therapy. After three formal cycles (9 weeks) of conversion therapy, the FLR/SLV ratio increased to 65%, and then right hepatectomy was performed. The lesion achieved a partial response (PR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. The second hepatectomy was successfully performed, and there was no recurrence during the 36-month postoperative follow-up. In this case, portal vein ligation (PVL) surgery, HAIC, and targeted immunotherapy contributed to the conversion therapy of HCC through different dimensions, including mechanical blood flow blockage, local chemotherapy, and immune regulation, laying the foundation for the safety of radical surgery and long-term postoperative survival.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"19 ","pages":"578577"},"PeriodicalIF":2.4,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and Validation of Multi-Omics Predictive Models for Colorectal Cancer Using Machine-Learning Approaches.","authors":"Zhenhuan Lu, Xiaowen Li, Zhiping Liang, Xiaocong Zhang, Yiyan Tan, Yinglan Kuang, Kang Li, Xiaofeng Zhu","doi":"10.2147/PGPM.S566928","DOIUrl":"10.2147/PGPM.S566928","url":null,"abstract":"<p><strong>Objective: </strong>To construct and externally validate a multi-omics nomogram that uses only routine clinicopathological variables to predict tumor mutational burden (TMB), microsatellite instability (MSI), NTRK/PIK3CA mutation status and overall survival (OS) in colorectal cancer (CRC).</p><p><strong>Methods: </strong>TCGA data (n=398) served as the training set and 120 consecutive CRC patients who underwent radical resection at Yuebei People's Hospital formed the prospective validation set. After z-score normalization, 21demographic, clinical and pathological features were screened for multicollinearity (VIF<5) and redundancy via least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation. Optimal hyper-parameters for each algorithm were tuned by nested 10-fold grid search. Four machine-learning algorithms, logistic regression (LR), support-vector machine (SVM), decision tree (DT) and random forest (RF), were compared by area under the receiver-operating-characteristic curve (AUC), F1 score and decision-curve analysis. The best model was externally validated and calibrated with bootstrapping.</p><p><strong>Results: </strong>The results showed that the TMB prediction model included in the MSI index had the best power when constructed by the RF method, with an area under the ROC curve value of 0.9597. For the MSI state prediction model which includes three indicators of TMB, had the best power when constructed by RF method, with AUC value of 0.8225. The <i>NTRK</i> and <i>PIK3CA</i> gene status prediction model, which included three indicators of TMB and MSI status, had the best power when constructed using the RF method.</p><p><strong>Conclusion: </strong>The prediction model constructed in this study can help clinicians quickly identify high-risk patients and provide a basis for formulating a reasonable treatment plan. Further optimization of the model and expansion of the sample size are required to verify its power in the future.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"19 ","pages":"566928"},"PeriodicalIF":2.4,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NAT2 Acetylation Phenotypes in India: A Narrative Review of Personalized TB Therapy.","authors":"Nikhat Khan, Manjari Jonnalagadda, Ravindra Kumar, Aparup Das","doi":"10.2147/PGPM.S568037","DOIUrl":"10.2147/PGPM.S568037","url":null,"abstract":"<p><p>Tuberculosis (TB) continues to be a significant health challenge in India, which necessitates accurate and personalized therapeutic strategies for its successful treatment. Polymorphisms in the N-acetyltransferase-2 (<i>NAT2</i>) enzyme, involved in metabolism of a first-line drug, isoniazid (INH), for treatment of TB, have three acetylation phenotypes (slow, intermediate, or fast) that influence drug efficacy, toxicity and treatment outcomes. This article is presented as a narrative review of current research retrieved from PubMed, Scopus, and Google Scholar, focusing on studies related to <i>NAT2</i> polymorphisms, pharmacogenomics, and tuberculosis therapy. The selected literature was reviewed to address the biological importance of the acetylation process and the development of DNA-based methods for genotyping of the <i>NAT2</i> gene and discussion of their clinical applications, as well as the effect of <i>NAT2</i> phenotypes on the treatment outcomes of TB. In addition, how highly genetic diversity in Indian populations necessitates the development of simplified and personalized medication therapy using population-based <i>NAT2</i> phenotyping approaches is discussed. The need for nationwide mapping of <i>NAT2</i> variants and the deployment of rapid, cost-effective genotyping platforms, especially in resource-limited endemic settings, are also emphasized. Moreover, how combining <i>NAT2</i> profiling with additional pharmacogenetic markers may lead to a comprehensive framework for TB treatment optimization is also discussed. It is envisioned that integration of all of these approaches under <i>NAT2</i>-guided therapy in India's National TB Elimination Programme (NTEP) might change the dynamics of TB management in India.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"19 ","pages":"568037"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatic Identification and Preliminary Validation of TP53, TGFB1, and NFE2L2 as Potential Ferroptosis-Related Regulators in Pancreatic Adenocarcinoma.","authors":"Shouying Li, Chunfang Zhang, Shengxiang Lv, Zhimei Zhang, Dazhou Xu, Tonglei Xu","doi":"10.2147/PGPM.S562602","DOIUrl":"10.2147/PGPM.S562602","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with very poor prognosis for patients. Ferroptosis, as a novel cell death mechanism, brings a new direction for PAAD therapeutic research.</p><p><strong>Methods: </strong>Ferroptosis-related differentially expressed genes were identified by bioinformatic analysis of the FerrDb, TCGA, and GTEx databases. A series of analyses, including functional enrichment, protein-protein interaction (PPI) networking, survival analysis, and immune infiltration profiling, were performed to screen for and characterize hub genes. Subsequently, the expression of key hubs-NFE2L2 (NRF2), TGFB1, and TP53-was validated in PDAC patient tissues and cell lines using qRT-PCR and Western blot. Their biological functions were investigated via shRNA-mediated knockdown in BxPC-3 cells, followed by assays for cell migration (wound healing, transwell) and ferroptosis (ROS, MDA, GSH/GSSG).</p><p><strong>Results: </strong>Bioinformatic analysis identified 221 ferroptosis-related DEGs. NFE2L2, TGFB1, and TP53 emerged as core hub genes whose high expression correlated with poor patient survival and specific immune infiltration patterns. Experimental validation confirmed that NRF2, TGFβ1, and TP53 proteins were significantly upregulated in PDAC tissues compared to adjacent normal tissues. Functionally, knockdown of NFE2L2 and TGFB1 suppressed PDAC cell migration, whereas TP53 knockdown enhanced it. Inversely, NFE2L2 knockdown promoted ferroptosis (increased ROS and MDA, decreased GSH), while knockdown of both TGFB1 and TP53 inhibited ferroptosis.</p><p><strong>Conclusion: </strong>TP53, TGFB1, and NRF2 are key ferroptosis-related regulators in PAAD, influencing tumor progression, ferroptosis sensitivity, and immune contexture. These findings provide new insights and potential targets for ferroptosis-based therapies in PAAD.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"19 ","pages":"562602"},"PeriodicalIF":2.4,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes of Osimertinib Combined with Platinum-Based Chemotherapy in EGFR-Mutant Non-Small Cell Lung Cancer: A Retrospective Study.","authors":"Ruixue Han, Xin Yu","doi":"10.2147/PGPM.S566952","DOIUrl":"10.2147/PGPM.S566952","url":null,"abstract":"<p><strong>Objective: </strong>To assess the clinical outcomes of osimertinib combined with platinum-based chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and to describe associated changes in angiogenesis-related and tumor marker levels.</p><p><strong>Methods: </strong>A retrospective analysis was performed on 112 NSCLC patients with EGFR-sensitive mutations treated from June 2018 to October 2020. Patients received either pemetrexed plus cisplatin (control group, n=56) or the same regimen with osimertinib (experimental group, n=56). Evaluation parameters included objective response rate (ORR), disease control rate (DCR), vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events.</p><p><strong>Results: </strong>ORR was comparable between groups (P>0.05), whereas the experimental group showed a significantly higher DCR (P<0.05). Post-treatment VEGF, Ang-2, CEA, and CYFRA21-1 levels decreased in both groups, with greater reductions observed in the experimental group (P<0.05). Median follow-up was 18.8 months. The experimental group demonstrated longer median PFS (15.7 vs 10.6 months, χ²=18.337, P<0.001) and OS (24.6 vs 17.5 months, χ²=24.679, P<0.001). The incidence of adverse reactions did not differ significantly between groups (P>0.05).</p><p><strong>Conclusion: </strong>In this retrospective cohort, the addition of osimertinib to platinum-based chemotherapy was associated with improved disease control and prolonged survival, along with greater reductions in angiogenesis-related and tumor marker levels, without increasing treatment-related toxicity.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"19 ","pages":"566952"},"PeriodicalIF":2.4,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-Translational Modifications of Histones and Non-Histones in Liver Disease and Traditional Chinese Medicine Treatment: A Narrative Review.","authors":"Zhuohua Xie, Yanting Deng, Xinru Zhang, Jieyi Chen, Jiasheng Deng, Yibin Fang, Xiaoxue Ye, Zhipin Zhou","doi":"10.2147/PGPM.S555701","DOIUrl":"10.2147/PGPM.S555701","url":null,"abstract":"<p><p>Post-translational modifications (PTMs) of histones and non-histones are significant epigenetic modifications in humans, including acetylation, methylation, phosphorylation, glycosylation, and ubiquitination. These modifications regulate chromatin structure and gene expression, enabling proteins to perform their normal biological functions within cells and maintain stable expression. It is also closely related to the development process of liver diseases and plays an important role in the pathological processes of liver cancer, liver fibrosis, alcoholic fatty liver disease and non-alcoholic fatty liver disease. This article reviews the roles and pathway mechanisms mediated by post-translational modifications of histones and non-histones in these liver diseases, and briefly outlines how traditional Chinese medicine (TCM) can intervene in liver diseases by modulating protein post-translational modifications, providing new strategies for future prevention and treatment of liver diseases.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"19 ","pages":"555701"},"PeriodicalIF":2.4,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Managing Refractory Hypertension: A Case Study Exploring the Influence of ACE and ACTN3 Gene Polymorphisms.","authors":"Benedikt Gasser, Alain Dössegger, Martin Flück","doi":"10.2147/PGPM.S528939","DOIUrl":"10.2147/PGPM.S528939","url":null,"abstract":"<p><p>The responses to Antihypertensive drugs vary among patients. The renal and muscular processes of blood flow regulation in peripheral blood vessels depend on the genetic and physiological constitution. Here, we present a case of an elderly female patient who experienced several phases of hypertensive emergencies during supervised training sessions. Hypertension treatment with different ACE inhibitors was discontinued because of severe side effects or simply no effect. Genotyping of ACE and ACTN3 gene polymorphisms helped find adequate antihypertensive treatment after all other approaches failed. The measured ACTN3-RR genotype indicated the possibility of a higher proportion of fast-twitch muscle fibers. This type of muscle fiber contributes to the generation of a high muscle force, which can compress the vascular bed more during physical work than slow muscle fibers. Therefore, a beta-blocker was used for treatment, allowing better vasodilative capacity. As reported by the patient, this pharmaceutical alone helped treat hypertensive emergencies adequately. Therefore, we believe that genetic information can help to identify optimal pharmaceutical treatments a problem that is highly prevalent in elderly subjects.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"18 ","pages":"287-294"},"PeriodicalIF":1.8,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12728420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Successful Surgical Resection of PVTT Vp4 Hepatocellular Carcinoma Following Hepatic Arterial Infusion Chemotherapy Combined with Cadonilimab Plus Donafenib.","authors":"Sizhi Chen, Yongguang Wei, Xiwen Liao, Chengkun Yang, Guangzhi Zhu, Chuangye Han, Hao Su, Tao Peng","doi":"10.2147/PGPM.S555061","DOIUrl":"10.2147/PGPM.S555061","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the potential and efficacy of hepatic artery infusion chemotherapy combined with the PD-1/CTLA-4 bispecific antibody cadonilimab and the multi-kinase inhibitor donafenib in conversion therapy for unresectable hepatocellular carcinoma (uHCC) with Vp4-type portal vein tumor thrombus(PVTT).</p><p><strong>Methods: </strong>We present a case report of a 41-year-old male diagnosed with diffuse hepatocellular carcinoma (HCC) in the right lobe of the liver and tumor thrombus involving the main portal vein. Following multidisciplinary team evaluation, the patient received conversion therapy consisting of hepatic artery infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin, in combination with cadonilimab and donafenib.</p><p><strong>Results: </strong>Post-treatment imaging demonstrated marked regression of intrahepatic tumors and complete resolution of the portal vein tumor thrombus. Serum alpha-fetoprotein (AFP) levels normalized, and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels showed a significant decline. Subsequently, a radical right hepatectomy was successfully performed, and postoperative pathological examination confirmed complete response. The patient experienced an uneventful recovery and remained free of tumor recurrence during the one-year follow-up period.</p><p><strong>Conclusion: </strong>The integrative treatment strategy combining HAIC with cadonilimab and donafenib demonstrates considerable promise as a conversion approach for patients with traditionally unresectable HCC with Vp4-type PVTT. This regimen may substantially improve oncological outcomes and enable curative resection. This case provides compelling evidence to support further clinical investigation of this multimodal therapeutic combination.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"18 ","pages":"279-286"},"PeriodicalIF":1.8,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12691647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}