Anti-Cancer Drugs最新文献

{"title":"Effect of valproic acid and levetiracetam administration on the survival of glioma patients: a meta-analysis study.","authors":"Arya Shirani, Mobin Obeidinia, Makan Ziafati, Javad Garavand, Moazzameh Ramezani, Fatemeh Ramezani","doi":"10.1097/CAD.0000000000001746","DOIUrl":"10.1097/CAD.0000000000001746","url":null,"abstract":"<p><p>In this meta-analysis study, the effect of valproate (VPA) and levetiracetam (LEV) on the survival of glioma patients taking temozolomide (TMZ) was investigated. The cumulative hazard ratios (HR) of overall survival (OS) and progression-free survival from published clinical studies were determined using a random effects model to estimate the strength of the association between VPA/LEV and survival in glioma patients. The results showed that VPA (data from 2304 patients from 14 clinical trial studies) and LEV (data from 1610 patients from 11 clinical trial studies) increase OS by 20% [HR = 0.80; 95% confidence interval (CI), 0.69-0.94; P  = 0.01] and 18% (HR = 0.82; 95% CI, 0.68-0.98; P  = 0.03), respectively. Use of VPA and LEV as anticonvulsant drugs increased the OS of patients with glioma taking TMZ to an almost equal extent. These findings need to be confirmed in larger prospective studies.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"749-758"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688616","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":"Dysfunction of core clock genes regulates malignant phenotype and gemcitabine sensitivity of cholangiocarcinoma cells.","authors":"Yin Li, Aimin Zheng, Yangang Cui, Tianbao Liu","doi":"10.1097/CAD.0000000000001744","DOIUrl":"10.1097/CAD.0000000000001744","url":null,"abstract":"<p><p>The circadian clock governs daily rhythms in numerous physiological processes through precise regulation of gene expression and biochemical functions. Dysregulation of the circadian rhythm has been implicated in carcinogenesis and cancer progression. However, the mechanisms by which the circadian clock influences cancer phenotype and chemotherapy resistance, particularly in cholangiocarcinoma (CCA), remain poorly understood. Using cell lines established from primary CCA and metastatic ascites of two male patients, we manipulated core clock genes ( BMAL1 , PER2 , and NR1D1 ) to evaluate their effects on circadian rhythms. We analyzed alterations in circadian phenotypes at dynamic and single time points and assessed their impact on cancer-related phenotypic changes, including proliferation, apoptosis, cell cycle regulation, migration, invasion, and the expression of epithelial-to-mesenchymal transition (EMT) and cancer stem cell markers. Additionally, we examined the impact of circadian disruption on gemcitabine sensitivity. Genetic deletion of BMAL1 , PER2 , and NR1D1 disrupted circadian rhythm and significantly altered cancer phenotypes. Notably, BMAL1 and NR1D1 impairment exacerbated cell migration, invasion, and EMT activation in CCA cells. BMAL1 loss also induced gemcitabine resistance. In contrast, PER2 repression enhanced chemosensitivity and inhibited metastasis. The modulation of the circadian gene triggered phenotypic changes in CCA cells, indicating a crucial involvement of core-clock components in the pathological mechanisms hastening bile duct cancer malignancy. Our findings advance the understanding of regulating CCA malignancy and may offer a novel target for its treatment.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"711-722"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315773","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":"Overcoming refractory leptomeningeal metastasis in nonsmall cell lung cancer with intrathecal pemetrexed and osimertinib: a case report.","authors":"Li Xue, Xuhui Zhao, Xiaohui Tai, XuXia Zhang, Lingfang Zhang, Hongling Li","doi":"10.1097/CAD.0000000000001748","DOIUrl":"10.1097/CAD.0000000000001748","url":null,"abstract":"<p><p>Leptomeningeal metastasis (LM), a devastating complication of advanced nonsmall cell lung cancer (NSCLC), severely compromises patient survival and quality of life. Currently, standardized diagnostic criteria and treatment protocols for NSCLC-associated LM remain undefined, posing significant clinical challenges. Here, we present a case of a 58-year-old female with advanced epidermal growth factor receptor (EGFR)-mutated (exon 19 deletion) lung adenocarcinoma who developed LM after failing first-line gefitinib therapy. Initial treatment with osimertinib (80 mg/day), a third-generation EGFR-tyrosine kinase inhibitor (TKI), achieved 8 months of disease control before LM progression. Cerebrospinal fluid genomic analysis revealed acquired EGFR mutations (exon19 L747-A750delins and exon18 L718Q). Combination therapy with intrathecal pemetrexed and standard-dose osimertinib temporarily alleviated neurological symptoms. Upon disease recurrence after 6 months, therapeutic intensification through increased intrathecal pemetrexed frequency and high-dose osimertinib (160 mg/day) resulted in sustained neurological improvement and prolonged survival with manageable toxicity. This case demonstrates the potential of optimized intrathecal/systemic TKI combination strategies for EGFR-mutant NSCLC with LM, providing clinical insights for this therapeutic dilemma.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"764-769"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636000","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":"LncRNA FOXP4-AS1 silencing inhibits metastasis and epithelial-mesenchymal transition in nasopharyngeal carcinoma via miR-136-5p/MAPK1: Erratum.","authors":"Jin Yan, Qi Zhou","doi":"10.1097/CAD.0000000000001726","DOIUrl":"10.1097/CAD.0000000000001726","url":null,"abstract":"","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":"36 9","pages":"775-776"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039101","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":"Progression of drug resistance or multiple primary lung cancer: a case report and literature review of a patient with mesenchymal-epithelial transition factor exon 14 skipping alterations lung adenocarcinoma.","authors":"Liang Gong, Lihang Zhou, Pan Yang, Fu Xiong, Xin Li, Chunlan Tang","doi":"10.1097/CAD.0000000000001747","DOIUrl":"10.1097/CAD.0000000000001747","url":null,"abstract":"<p><p>Mesenchymal-epithelial transition factor (MET) exon 14 skipping alterations are rare mutations in non-small-cell lung cancer, associated with high malignancy and poor prognosis. This article presents a case of a patient diagnosed with advanced left upper lung adenocarcinoma characterized by a MET14 skipping mutation. Following first-line treatment with crizotinib, there was a significant reduction in the size of the primary lesion; however, during the course of treatment, an increase in size and prominence of solid components were observed in the right upper lung lesion. A biopsy and subsequent genetic testing revealed an epidermal growth factor receptor L858R mutation in the right upper lung adenocarcinoma, indicating the presence of multiple primary lung cancers. The patient opted against surgical intervention and local treatments, choosing instead a combination therapy regimen that included almonertinib and crizotinib. This treatment approach led to a significant reduction in the size of the right upper lung lesion. The patient's condition has remained stable without any signs of progression, resulting in an overall survival duration exceeding 53 months.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"759-763"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282230","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":"FH-2001 is a novel FGFR/VEGFR dual inhibitor with immune-modulating activity.","authors":"Aiguo Liu, Longfei Huang, Xin Gao, Lei Liu, Xiang Li, Xiaohong Yu, Chunyan Zhao","doi":"10.1097/CAD.0000000000001743","DOIUrl":"10.1097/CAD.0000000000001743","url":null,"abstract":"<p><p>Multiple cancers are driven by aberrant fibroblast growth factor receptor (FGFR) signaling and vascular endothelial growth factor receptor (VEGFR)-linked angiogenesis. Several therapeutic agents targeting FGFR and VEGFR have been developed and approved for use in solid cancers; however, there is still a high unmet medical need for new agents that have a more powerful antitumor activity and a broader antitumor spectrum. Here, we report the discovery of FH-2001, a novel and potent FGFR/VEGFR dual inhibitor, with additional activity of modulating programmed cell death ligand 1 (PD-L1) gene expression. In biochemical assays, FH-2001 showed potent inhibition of FGFR1, 2, 3, and 4, with half-maximal inhibitory concentration (IC 50 ) of 0.2, 0.2, 0.4, and 2.0 nM, respectively, and VEGFR1, 2, and 3, with IC 50 values of 2.0, 0.3, and 0.5 nM, respectively. FH-2001 significantly suppressed the cell growth of FGFR- or VEGFR-driven cancer cell lines. In representative cell line- and patient-derived tumor xenografts with aberrant FGFR or VEGFR signaling, FH-2001 substantially inhibited tumor growth. Furthermore, FH-2001 demonstrated marked antitumor activities when treated alone or combined with PD-L1 or PD-1 antibody in syngeneic mouse models. Flow cytometric analysis revealed that FH-2001 alone or in combination with anti-PD-L1 increased T and natural killer cells and decreased myeloid cells in the tumor microenvironment. Mechanistically, FH-2001 treatment dramatically reduced c-Myc and PD-L1 mRNA and protein levels in a dose-dependent manner in vitro . Taken together, FH-2001 is a promising dual-target inhibitor of FGFR and VEGFR and also modulates cancer immunity, while its robust antitumor activity positions it as a potentially class-leading anticancer agent.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"703-710"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473842","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":"The mTOR pathway inhibition with everolimus in pseudomyogenic hemangioendothelioma harboring SERPINE1-FOSB gene fusion: a case report and review of the literature.","authors":"Cevat İlteriş Kikili, Bahadir Köylü, Fatih Kemik, Nazan Demir, Mehmet Ali Deveci, Fatih Selçukbiricik","doi":"10.1097/CAD.0000000000001752","DOIUrl":"10.1097/CAD.0000000000001752","url":null,"abstract":"<p><p>Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare tumor that is frequently misdiagnosed as other vascular or soft tissue neoplasms and typically follows an indolent course. Due to its locally aggressive and multifocal nature, surgical intervention is often not feasible. Moreover, conventional chemotherapy has shown limited efficacy according to existing literature. Recent advances in genetic profiling have identified a SERPINE1/FOSB gene fusion in PHE, leading to the activation of the mechanistic target of rapamycin (mTOR) pathway. This discovery has highlighted mTOR inhibitors and multityrosine kinase inhibitors as promising therapeutic options. In this report, we present a PHE case with confirmed SERPINE1/FOSB fusion who was initiated on everolimus therapy, along with a review of the current literature.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"770-774"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551781","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 and optimization of oxidative phosphorylation inhibitors from a phenotypic screen.","authors":"Mahmoud El Shemerly, Florian Richalet, Dimitri Robay, Claude Nuoffer, Alexandra Kunz, Luc Bury, Claire Hisler, Norbert Hermann, Jochen Spickermann, Sven Weiler, Paul M J McSheehy, Laurenz Kellenberger, Heidi A Lane","doi":"10.1097/CAD.0000000000001750","DOIUrl":"10.1097/CAD.0000000000001750","url":null,"abstract":"<p><p>Tumor metabolism and metabolic reprogramming in cancer cells represent a promising area in oncology research, offering new avenues for therapeutic intervention. While the 'Warburg effect' highlights the reliance of many tumors on aerobic glycolysis, emerging evidence indicates that some cancers also depend on mitochondrial oxidative phosphorylation (OXPHOS) for energy production, cancer cell survival, tumor progression, metastasis, and drug resistance. We conducted a high-throughput, differential, phenotypic screening followed by a focused medicinal chemistry campaign, leading to the identification of novel, potent OXPHOS inhibitors. These lead compounds selectively target complex I of the mitochondrial electron transport chain, thereby disrupting ATP production and oxygen consumption in cancer cells. In-vitro studies in breast cancer cell lines, along with published data, suggest that MCT4 expression may serve as a biomarker for drug sensitivity. Notably, low MCT4 expression correlated with higher potency in cell growth assays. The identified compounds exhibited favorable drug-like properties, including good pharmacokinetics and oral bioavailability in mice. Daily oral dosing significantly inhibited tumor growth in two in-vivo breast cancer models with low MCT4 expression levels. This efficacy, however, was accompanied by body weight loss, indicating the need to enhance the therapeutic index through optimization or rational combination therapy strategies. These findings highlight the therapeutic potential of targeting mitochondrial OXPHOS in cancers with defined metabolic dependencies, offering a novel approach for exploiting tumor-specific metabolic vulnerabilities for improved cancer treatment.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"731-741"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332342","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":"Exploring natural products for allosteric inhibition of glutathione peroxidase 4 in drug-resistant cancers via molecular docking and dynamics.","authors":"Mohammad Yasir, Jeevan Patra, Rahul K Maurya, Alok S Tripathi, Hero Khan Pathan","doi":"10.1097/CAD.0000000000001749","DOIUrl":"10.1097/CAD.0000000000001749","url":null,"abstract":"<p><p>Glutathione peroxidase 4 (GPX4) plays a pivotal role in regulating ferroptosis and maintaining redox homeostasis, making it a critical target in drug-resistant cancers. Recent studies suggest that allosteric inhibition of GPX4 could overcome resistance mechanisms. This study aimed to identify natural products with potential allosteric inhibition of GPX4 using computational approaches. A comprehensive virtual screening was conducted on a curated library of 125 415 natural compounds derived from the COlleCtion of Open Natural ProdUcTs (COCONUT) database. Structure-based virtual screening and molecular docking were performed against the allosteric site of GPX4 (PDB ID: 7U4N) using UCSF DOCK6. The top candidates were evaluated through binding free energy calculations [molecular mechanics Poisson-Boltzmann surface area (MM-PBSA)] and 100 ns molecular dynamics simulations using the AMBER20 package. Pharmacokinetic and toxicity profiles were assessed through absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. Five natural compounds - quercetin, zeatinriboside, ribofuranosylmakaluvic acid C, tecleanatalensine B, and scopolamine - exhibited superior binding affinities (docking scores ranging from -4.01 to -4.95 kcal/mol) compared with the cocrystallized ligand (-3.15 kcal/mol), with significant interactions at the key Cys66 residue of GPX4. MM-PBSA analysis revealed highly favorable binding free energies (up to -37.94 kcal/mol), indicating stable ligand-protein complexes. Molecular dynamic simulations confirmed structural stability, with minimal root mean square deviation and root mean square fluctuations. ADMET profiling suggested favorable solubility, absorption, low toxicity, and good drug-likeness. This study highlights the potential of natural products as allosteric inhibitors of GPX4. The identified compounds demonstrated strong and stable interactions with the GPX4 allosteric site and possessed desirable pharmacokinetic properties, warranting further in-vitro and in-vivo investigations for potential development as anticancer agents targeting drug-resistant cancers.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"723-730"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473841","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":"Serum heat shock protein family A member 9 protein as a biomarker for bortezomib resistance and poor prognosis in patients with multiple myeloma.","authors":"Lin Chen, Shuang Gao, Li Lin, Su Liu, Jing Ma, Zhiying Zhang, Qian Li","doi":"10.1097/CAD.0000000000001764","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001764","url":null,"abstract":"<p><p>Bortezomib resistance in multiple myeloma (MM) is a significant clinical challenge that limits the long-term effectiveness. Currently, there is a lack of reliable biomarkers to predict bortezomib resistance. Previous studies reported that several proteins regulate bortezomib resistance through targeting ubiquitin-proteasome pathways, including heat shock protein family A member 9 (HSPA9), dickkopf Wnt signaling pathway inhibitor 1 (DKK1), proteasome 26S subunit non-ATPase 14 (PSMD14), and tripartite motif containing 21 (TRIM21). In our study, we aimed to analyze the expression of these proteins in MM patients and evaluate their potential as biomarkers for bortezomib resistance. Our study enrolled 46 newly diagnosed MM patients (38 bortezomib-sensitive and eight bortezomib-resistant patients) and 52 healthy controls, and serum samples were collected from the patients before initial treatments. The levels of HSPA9, DKK1, PSMD14, and TRIM21 proteins in serum samples were measured using ELISA. The diagnostic power of HSPA9 protein for bortezomib resistance was evaluated through receiver operating characteristic curves combined with the area under curve (AUC). The correlation between HSPA9 protein and clinicopathological features was examined using the chi-square test, and Kaplan-Meier method and Cox regression analysis were applied to assess prognostic value. Compared with healthy controls, increased HSPA9 and DKK1, but decreased TRIM21 protein expression, were observed in serum samples from MM patients. There was no statistical difference in PSMD14 protein expression between the two groups. Notably, compared with bortezomib-sensitive patients, only HSPA9 protein was found to be upregulated in bortezomib-resistant patients, whereas no differences were found in the other proteins. Furthermore, the AUC of serum HSPA9 for differentiating MM patients from healthy controls was 0.906 [95% confidence interval (CI): 0.843-0.968]. And serum HSPA9 expression could effectively differentiate bortezomib-resistant MM patients from bortezomib-sensitive MM patients, with an AUC of 0.845 (95% CI: 0.734-0.957). In addition, elevated serum HSPA9 expression positively correlated with advanced International Staging System stage, increased β2-MG, abnormal immunoglobulin, and bortezomib resistance. Higher serum HSPA9 was linked to shorter overall survival rate and independently predicted poor prognosis. Our study demonstrated that elevated serum HSPA9 protein serves as a potential biomarker for bortezomib resistance and poor prognosis in MM patients.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013651","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}