Anti-Cancer Drugs最新文献

{"title":"Fibroblast growth factor receptor 2 mutation-guided targeted therapy with lenvatinib in sebaceous carcinoma of the external auditory canal: a case report and literature review.","authors":"RuGang Zhao, Qing Han, JuYi Wen, XinHong Zhang, Wei Qiu, ShanShan Wu, LiPin Gao, XiangFei Zhao","doi":"10.1097/CAD.0000000000001797","DOIUrl":"10.1097/CAD.0000000000001797","url":null,"abstract":"<p><p>This is the first global report of a successful case of lenvatinib treatment for a rare sebaceous carcinoma originating in the external auditory canal. The patient experienced local recurrence and pulmonary metastasis despite undergoing surgery and radiotherapy. Initial chemotherapy combined with immune checkpoint inhibitors achieved short-term stability, but the disease eventually progressed. Genetic testing revealed an Fibroblast growth factor receptor 2 (FGFR2) mutation, leading to a switch to targeted therapy with lenvatinib combined with capecitabine, demonstrating the value of targeted therapy in the management of rare, refractory sebaceous carcinoma.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"407-409"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival advantage of bevacizumab rechallenge in recurrent ovarian cancer regardless of platinum sensitivity.","authors":"Ugur Ozberk, Selin Akturk Esen, Serhat Sekmek, Ismet Seven, Oznur Bal, Efnan Algin, Sebnem Yucel, Dogan Uncu","doi":"10.1097/CAD.0000000000001798","DOIUrl":"10.1097/CAD.0000000000001798","url":null,"abstract":"<p><p>Bevacizumab has demonstrated significant efficacy in both first-line and recurrent settings of epithelial ovarian cancer; however, evidence regarding the benefit of bevacizumab retreatment after prior exposure in real-world populations remains limited. This study aimed to evaluate the efficacy of bevacizumab retreatment compared with nonbevacizumab regimens in recurrent metastatic ovarian carcinoma, irrespective of platinum sensitivity status. This retrospective single-center study included 133 patients with recurrent epithelial ovarian cancer who had previously received bevacizumab-containing first-line therapy between January 2015 and May 2025. Patients were grouped according to second-line treatment: bevacizumab-containing chemotherapy ( n  = 51) or chemotherapy alone ( n  = 82). Patients undergoing secondary cytoreductive surgery were excluded. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression models. Median PFS-2 after second-line treatment was significantly longer in the bevacizumab group compared with the nonbevacizumab group (9.7 vs. 3.0 months; P  < 0.001). This benefit was consistent across both platinum-sensitive and platinum-resistant subgroups. Multivariate analysis confirmed that omission of bevacizumab independently predicted worse PFS-2 (hazard ratio = 3.33, 95% CI: 2.17-5.11, P  < 0.001). Although OS-2 was numerically longer in the bevacizumab group (14.1 vs. 8.2 months), the difference was not statistically significant ( P  = 0.091). Bevacizumab retreatment following prior first-line use was associated with improved PFS regardless of platinum sensitivity, suggesting a potential survival advantage in recurrent ovarian cancer. Prospective, randomized studies including both platinum-sensitive and platinum-resistant patients with larger sample sizes are warranted to confirm these findings and determine the optimal use of bevacizumab beyond first-line therapy.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"359-365"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of an orally active and liver-targeted dual prodrug of 5-fluoro-2'-deoxyuridine-5'-monophosphate for the treatment of hepatocellular carcinoma.","authors":"Ming Yang, Xing-Long Dai, Cheng-Wei He, Han-Xuan Fang, Jin Yan, Ruo-Xin Bai, Jie Hao, Zhi-Meng Sun, Xiao-Hui Liu, Shu-Xiang Cui, Wen-Jin Wan, Jie-Jie Hao, Xian-Jun Qu","doi":"10.1097/CAD.0000000000001829","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001829","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy with 5-fluorouracil (5-FU) have been considered; however, it has limited survival benefits because of unbearable toxicity. Hence, a series of 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) prodrugs was designed and synthesized using ProTide technology. By favorable membrane permeability and bypassing enzymatic activation pathway of 5-FU to FdUMP, DL series of ProTide prodrugs circumvented mechanisms of 5-FU resistance and avoided the generation of associated toxic catabolites, resulting in enhanced anti-HCC efficacy and weak toxicity. Antiproliferative activity of compounds was evaluated in both human HCC cell lines and normal hepatocytes. Further anti-HCC activity was assessed in nude mice xenografted human HepG2, HUH7, or histidine triad nucleotide-binding protein 1 (HINT1) knockdown HUH7 cells orthotopically or subcutaneously. Mechanistic studies involving HINT1-silenced cells and co-administration with HINT1 upregulation by taraxasterol were conducted to validate the mode of action. Compound DL-2 effectively inhibited HCC cell growth but exhibited minimal cytotoxicity toward normal hepatocyte cell lines. DL-2 exhibited anticancer activity through bioactivation into FdUMP by hepatic HINT1. Comparatively, DL-2 weakly inhibited the orthotopic xenograft derived from HINT1-silenced human HUH7 cells. Systemic use of DL-2 did not produce significant toxicity in mice. In conclusion, we discovered an orally active and liver-targeted dual prodrug of FdUMP for the treatment of HCC. DL-2 is a promising drug used as a substitute for hepatic arterial infusion chemotherapy regimen.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibiting FGFR by toadflax reverses erlotinib resistance in nonsmall cell lung cancer.","authors":"Bateer Han, Ying Ma, Shuguang Bao, Hui Gao, Yanqing Gao, Qiang Guo, Ao Li, Meitao Li, Rong Yu, Hongwei Wang","doi":"10.1097/CAD.0000000000001649","DOIUrl":"10.1097/CAD.0000000000001649","url":null,"abstract":"<p><p>This study aims to demonstrate the effect of toadflax (bufalin) on erlotinib resistance in nonsmall cell lung cancer (NSCLC) by inhibiting the fibroblast growth factor receptor (FGFR). The microfluidic mobility transferase and caliper mobility-shift assays were employed to detect the FGFR inhibition by bufalin and the binding reversibility. Further, the inhibitory effects of bufalin were determined in HCC827 and HCC827/ER cells in vitro , investigating relative FGFR overexpression by quantitative reverse transcriptase-PCR (RT-qPCR) and FGFR downstream proteins, that is, FGFR substrate 2 (FRS2), extracellular signal-regulated kinase (ERK), and S6 by western blot analysis. Finally, HCC827/ER-inoculated xenograft tumors were constructed to observe the effects of bufalin and bufalin + erlotinib intervention on tumor growth. Bufalin inhibited FGFR by reversibly binding to FGFR1. In addition, the western blot analysis indicated a significant reduction in the expression levels of FGFR, FRS2, ERK, and S6 proteins in HCC827 and HCC827/ER cells, increasing the expression levels of apoptotic caspase-3 and poly-(ADP-ribose) polymerase proteins. Bufalin + erlotinib combination significantly inhibited the apoptosis of HCC827/ER cells and subsequent tumor growth in vivo . In addition, FGFR overexpression significantly reversed the sensitivity of bufalin to HCC827/ER cells, promoting the value-addition of HCC827/ER cells. Further, bufalin + erlotinib significantly reduced the growth of erlotinib-resistant HCC827/ER tumors, induced apoptosis, and inhibited the expression of FGFR and p-ERK proteins. These findings indicated that bufalin could reverse the erlotinib resistance in NSCLC by inhibiting the FGFR expression.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"301-311"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eugenol as a game-changer: overcoming osimertinib resistance in non-small cell lung cancer by inhibiting glycolysis via the tripartite motif containing 59/extracellular signal-regulated kinase pathway.","authors":"Kun Zhao, Wei Wang, Yansha Sun, Ke Li","doi":"10.1097/CAD.0000000000001793","DOIUrl":"10.1097/CAD.0000000000001793","url":null,"abstract":"<p><p>Eugenol plays a significant role in various cancers and can influence the sensitivity of cancer cells to chemotherapy. This study aimed to investigate the mechanism by which eugenol regulates glycolysis through the tripartite motif containing 59 (TRIM59)/extracellular signal-regulated kinase (ERK) pathway in osimertinib-resistant non-small cell lung cancer (NSCLC). Drug-resistant lung cancer cell lines were established using osimertinib and treated with eugenol at different concentrations for 24 h. After treatment with eugenol, siTRIM59, TRIM59 overexpression, and the ERK inhibitor, either alone or in combination, the cell counting kit-8 was used to assess cell viability in drug-resistant cell lines. Flow cytometry, colony formation assay, and transwell assays were employed to evaluate the effects of eugenol on cell apoptosis, clonogenic ability, migration, and invasion, respectively. Relevant kits were used to measure the glycolytic activity of the cells. Eugenol inhibited the proliferation, invasion, and migration of drug-resistant cells, promoted apoptosis, and reduced glucose consumption, lactate release, and glycolytic activity in drug-resistant cells. TRIM59 expression was higher in drug-resistant cancer cells, while eugenol treatment inhibited the expression of TRIM59 and ERK phosphorylation. Silencing of TRIM59 enhanced the effect of eugenol on drug-resistant cell lines. Overexpression of TRIM59 reversed the effects of eugenol on drug-resistant cell lines, whereas ERK inhibition reversed the effects of TRIM59 and enhanced the therapeutic effects of eugenol on cancer cells. Moreover, eugenol inhibited the tumor growth, TRIM59 expression, and ERK phosphorylation in osimertinib-treated mice. Eugenol can effectively overcome osimertinib resistance in NSCLC by regulating glycolysis through the TRIM59/ERK signaling pathway. Eugenol could serve as a promising adjunctive therapy to improve chemotherapy efficacy and overcome drug resistance in NSCLC.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"312-328"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720537","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":"Hematopoietic progenitor kinase 1 inhibitor BGB-15025 induces apoptosis in acute myeloid leukemia cells through the cell cycle pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway signaling axis.","authors":"Shiyu Yang, Fenglin Li, Haihui Zhuang, Dong Chen, Xia Jiang, Yanhan Zhou, Renzhi Pei, Shuangyue Li, Peipei Ye, Ying Lu","doi":"10.1097/CAD.0000000000001794","DOIUrl":"10.1097/CAD.0000000000001794","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy originating from the malignant clonal proliferation of hematopoietic stem/progenitor cells and is associated with a poor prognosis. Hematopoietic progenitor kinase 1 (HPK1, MAP4K1), a member of the MAP4K family, plays a critical role in immunomodulation and oncogenesis. Previous studies have highlighted its pro-oncogenic function in AML, suggesting its potential as both a prognostic marker and therapeutic target. This study aimed to investigate the anti-AML effects of the novel HPK1 inhibitor BGB-15025. We utilized preclinical models, including AML cell lines, primary patient-derived cells, and MV4-11 xenograft mice. Mechanistic investigations were conducted using RNA sequencing and Western blot analysis. BGB-15025 exerted potent cytotoxicity against AML cells and primary progenitors, inducing apoptosis and G0/G1 cell cycle arrest via downregulation of cyclin D1-cyclin-dependent kinase 4 and upregulation of P21. The inhibitor suppressed mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling through reduced phosphorylation of P38 and ERK. In-vivo studies demonstrated a reduced leukemia burden in xenograft models. This study is the first to elucidate that BGB-15025 triggers AML apoptosis through cell cycle blockade and MAPK pathway inhibition, thereby proposing a novel precision therapeutic strategy with significant clinical translational value.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"329-342"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916651","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":"Treatment of HRD-positive elderly ovarian cancer patient: a case report.","authors":"Yuxin Jiang, Qijun Yi, Yueer Wang, Chen Li, Haiyan Liu","doi":"10.1097/CAD.0000000000001772","DOIUrl":"10.1097/CAD.0000000000001772","url":null,"abstract":"<p><p>The standard treatment for advanced ovarian cancer follows a comprehensive 'surgery-chemotherapy-maintenance therapy' mode, typically involving initial cytoreductive surgery aiming for R0 resection, six cycles of platinum-based chemotherapy, followed by maintenance therapy for those who have responded well to the treatment. However, frailty and high incidence of comorbidities in elderly patients often compromise surgical outcomes, necessitate chemotherapy dose reductions, and limit maintenance therapy continuation, resulting in a poor prognosis. Poly (Adenosine diphosphate (ADP)-ribose) polymerase inhibitors (PARPi) have revolutionized the management strategy of homologous recombination deficiency (HRD)-positive patients as a groundbreaking advancement in first-line maintenance therapy. Fluzoparib, the domestically developed PARPi in China, has demonstrated significant efficacy in BRCA-mutated ovarian cancer. In the field of supportive care, megestrol acetate (MA) is recommended as the first-line preferred therapeutic agent for cancer-related anorexia by major guidelines, though its role in first-line ovarian cancer therapy remains unexplored, and evidence for its combination with PARPi is lacking. This article reported a case of an 89-year-old female patient with high-grade serous ovarian carcinoma. Due to intolerance to surgery and chemotherapy, an innovative first-line primary treatment regimen combining fluzoparib with MA was initiated based on BRCA2 mutation and HRD-positive status. Imaging assessments revealed significant tumor reduction without disease progression or grade ≥3 adverse events observed throughout follow-up. This case highlights the potential of combining PARPi and hormone therapy as a 'chemotherapy-free' precision treatment model for elderly and HRD-positive ovarian cancer patients, offering a promising strategy to balance efficacy and tolerability in a population traditionally underserved by conventional regimens.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"352-357"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627982","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":"Interferon regulatory factor 4 drives M2 macrophage polarization in lung adenocarcinoma via the absent in melanoma 2-mediated phosphoinositide 3-kinase/protein kinase B signaling pathway.","authors":"Xiaoyun Zou, Qing Ji, Zhongzheng Wen, Limei Lei, Xuan Chen, Wen Hu","doi":"10.1097/CAD.0000000000001795","DOIUrl":"10.1097/CAD.0000000000001795","url":null,"abstract":"<p><p>Tumor-associated macrophages, predominant immunosuppressive components within the tumor microenvironment, critically regulate lung adenocarcinoma (LUAD) progression; however, their molecular regulatory mechanisms remain incompletely characterized. The Cancer Genome Atlas database analysis revealed absent in melanoma 2 (AIM2) expression in LUAD. The correlation between AIM2 expression and M2 macrophage infiltration levels was further evaluated. Putative transcriptional regulators upstream of AIM2 were predicted through bioinformatics screening, with JASPAR employed to identify potential binding sites between candidate factors and the AIM2 promoter. These predictions were experimentally validated using dual-luciferase reporter assays. Furthermore, we established a LUAD cell-macrophage coculture system. We performed flow cytometric analysis of macrophage surface CD206 expression, quantitative PCR quantification of mRNA levels, ELISA quantification of cytokine secretion profiles, and Western blot detection of proteins. Bioinformatics analysis revealed that AIM2 was highly expressed in LUAD tumor tissues and positively correlated with the marker genes of M2 macrophages. Overexpression of AIM2 in LUAD cells promoted the expression of CD206 on the macrophage surface, upregulated the mRNA expression levels of M2 macrophage marker genes such as CD163 , ARG1 , and MRC1 , and enhanced the secretion of transforming growth factor-beta and interleukin-10 . These results indicated an increased level of macrophage polarization towards the M2 phenotype, and inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway reversed the above phenomenon. Furthermore, the interferon regulatory factor 4 (IRF4) promoted the transcription of AIM2. IRF4 knockdown in LUAD cells suppressed M2 macrophage polarization, but simultaneous overexpression of AIM2 restored it to baseline levels. IRF4 drives M2 macrophage polarization in LUAD via the AIM2-mediated PI3K/AKT signaling pathway.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"343-351"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145817463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inavolisib and lenvatinib for PIK3CA-mutated refractory splenic angiosarcoma: a case report.","authors":"Xinyue Zhao, Chenyu Wang, Yuping Ge, Dongfeng Song, Ai Guan, Jing Hu, Yuxue Nie, Mei Guan","doi":"10.1097/CAD.0000000000001831","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001831","url":null,"abstract":"<p><p>Primary splenic angiosarcoma (PSA) is a rare vascular malignancy with a poor prognosis and limited therapeutic options. A 62-year-old man with metastatic PSA underwent splenectomy followed by first-line paclitaxel, achieving stable disease for 7 months. Disease progression manifested as hepatic and bone marrow metastases with tumor-induced hepatic failure and refractory thrombocytopenia. Sequential treatment with liposomal doxorubicin, eribulin, toripalimab, and lenvatinib failed to control the disease failed to control the disease. Genomic profiling identified a PIK3CA p.P471L missense mutation. A combination regimen of inavolisib (a selective PI3Kα inhibitor) and lenvatinib was initiated. Bilirubin levels normalized, and platelet counts recovered within 2 weeks; follow-up MRI confirmed radiological stabilization. At 16 months postdiagnosis, the patient remains alive on this regimen, though long-term durability of response has yet to be determined. To our knowledge, this is the first reported use of inavolisib in angiosarcoma. The rapid biochemical and radiological response observed in this PIK3CA-mutated PSA supports early genomic profiling to identify actionable alterations and warrants prospective evaluation of combined phosphoinositide 3-kinase and vascular endothelial growth factor pathway inhibition in refractory angiosarcoma.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug repurposing of liver cancer based on multimodal neural network and virtual screening.","authors":"Xu Huang, Xiaoqian Jia, Yu Zhou, Zhiguang Chang, Xiaobo Zhang","doi":"10.1097/CAD.0000000000001827","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001827","url":null,"abstract":"<p><p>Liver cancer is a malignant tumor with high incidence and mortality rates globally. Existing therapeutic methods have certain limitations in terms of efficacy, safety, and applicability, creating an urgent need for the development of new treatment strategies. Drug repurposing, which explores new indications for already approved drugs, offers significant advantages in reducing research and development costs and shortening development timelines. This study utilized a multimodal neural network model to integrate molecular fingerprints and molecular graphs to construct a drug-target interaction prediction system for liver cancer targets. A large-scale virtual screening of The US Food and Drug Administration-approved drugs was conducted, followed by molecular docking and molecular dynamics simulations to analyze binding stability. The screening identified 17 potential antiliver cancer drugs. Further verification of their in-vitro activity was performed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and wound healing assays in MHCC97-H, HepG2, and Huh7 cell lines, revealing that Manidipine and Vildagliptin exhibited significant cytotoxicity and migration inhibition. These results demonstrate the feasibility of the proposed screening workflow and provide a set of candidate molecules for further mechanistic investigation in liver cancer drug repurposing.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}