Anti-cancer agents in medicinal chemistry最新文献

{"title":"Pulsatilla chinensis Saponins as Multitargeted Anticancer Agents: A Mini-Review of Molecular Mechanisms and Therapeutic Potential.","authors":"Jizhuo Sun, Fangfang Nie, Xue Sun, Yuanhe Wang","doi":"10.2174/0118715206463897260603152039","DOIUrl":"10.2174/0118715206463897260603152039","url":null,"abstract":"<p><strong>Introduction: </strong>This review comprehensively summarizes the multi-target antitumor molecular mechanisms and therapeutic potential of key triterpenoid saponins Anemoside B4 (AB4), Pulsatilla Saponin D (PSD), Pulsatilla Saponin A (PSA), PC saponin (PC), and Anemoside A3 (AA3) derived from Pulsatilla chinensis.</p><p><strong>Methods: </strong>Relevant literature across major databases up to early 2025 was systematically reviewed, categorizing findings by saponin type to analyze structure-activity relationships. Additionally, a Pan-Assay Interference Compounds (PAINS) analysis was conducted using the SwissADME platform to verify the target specificity of their core structures.</p><p><strong>Results: </strong>These saponins exhibit highly structure-dependent, specific anticancer mechanisms. Specifically, AB4 induces apoptosis and autophagy; PSD inhibits angiogenesis and blocks autophagic flux; PSA triggers DNA damage responses and cell cycle arrest; PC saponins disrupt tumor glycolytic energy metabolism; AA3 remodels the tumor immune microenvironment by promoting anti-tumor M1 macrophage polarization. The PAINS analysis confirmed that these effects originate from specific target modulation rather than non-specific membrane disruption.</p><p><strong>Discussion: </strong>The precise mechanisms observed demonstrate that subtle structural variations in the saponin backbone dictate specific signaling outcomes. Crucially, the exclusion of pan assay interference compounds (PAINS) confirms that these biological effects stem from specific target modulation rather than non-specific membrane disruption. These findings highlight the pleiotropic advantage of Pulsatilla saponins, allowing them to simultaneously intervene in multiple oncogenic signaling pathways and overcome potential drug resistance.</p><p><strong>Conclusion: </strong>Pulsatilla saponins represent promising multi-target anticancer candidates. Future studies should focus on improving their pharmacokinetic properties and delivery systems to facilitate clinical translation.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343778","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 Serum Exosomal Protein Biomarkers for Early- and Late-Stage Lung Cancer Through Comparative Proteomic Analysis.","authors":"Dong Zeng, Xiaoli Huang, Haicheng Tang, Mingsheng Chen, Jingjing Xu, Yuhan Shi, Shu Song","doi":"10.2174/0118715206418059250915054635","DOIUrl":"10.2174/0118715206418059250915054635","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) exhibits distinct immune microenvironments in early-stage (ES-LUAD), advanced-stage (AS-LUAD), and pneumonia (PNA). Tumor-derived exosomes facilitate intercellular communication and contribute to the development and progression of tumors.</p><p><strong>Objectives: </strong>This study aims to comprehensively profile and compare the serum exosomal proteome across ESLUAD, AS-LUAD, and PNA patients, identify differentially expressed exosomal proteins (DEEPs) with potential as stage-specific diagnostic and prognostic biomarkers, and elucidate the biological pathways associated with LUAD progression through functional enrichment analysis of the identified DEEPs.</p><p><strong>Methods: </strong>Exosomes were extracted from blood samples and characterized using TEM, NTA, and Western blotting. Proteomic analysis was performed via LC-MS-MS, and differentially expressed genes (DEGs) were analyzed using hierarchical clustering, Gene Ontology (GO), and KEGG pathway analysis.</p><p><strong>Results: </strong>Distinct exosomal protein signatures were identified across LUAD stages and PNA. CD81 and IGLV7- 46 were identified as potential biomarkers for early detection, staging, and prognosis. GO analysis revealed significant dysregulation in immune response, leukocyte activation, and response to stimuli, with cellular components implicating the extracellular matrix and cell-cell interactions. KEGG analysis highlighted differences in adrenergic signaling.</p><p><strong>Discussion: </strong>This study aims to comprehensively profile and compare the serum exosomal proteome across ESLUAD, AS-LUAD, and PNA patients; identify differentially expressed exosomal proteins (DEEPs) with potential as stage-specific diagnostic and prognostic biomarkers; and elucidate the biological pathways associated with LUAD progression through functional enrichment analysis of identified DEEPs.</p><p><strong>Conclusion: </strong>Stage-specific serum exosomal protein alterations reflect LUAD biology and show strong potential as non-invasive diagnostic and prognostic biomarkers, advancing understanding and offering tools for early detection and monitoring. Clinical validation is still required.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343573","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":"Efficacy and Safety of Pembrolizumab as Monotherapy and in Combination with Chemotherapy versus Chemotherapy Alone for Advanced Gastric or Gastroesophageal Junction Cancer: A Systematic Review and Meta-Analysis.","authors":"Zhiqiang Bai, Zujun Ding, Shu Yang, Kaixin Du, Lei Deng, Yechao Qian, Hang Li","doi":"10.2174/0118715206460547260531205346","DOIUrl":"10.2174/0118715206460547260531205346","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to assess the effectiveness and safety of pembrolizumab, used either as a monotherapy or in combination with chemotherapy, compared to chemotherapy alone in patients with advanced Gastric Cancer (GC) or Gastroesophageal Junction (GEJ) cancer.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted in Web of Science, PubMed, and Embase up to October 13, 2025. Included were Randomized Controlled Trials (RCTs) involving adults with pathologically confirmed advanced GC/GEJ cancer that compared pembrolizumab-based regimens to chemotherapy alone. Data were pooled using random-effects models, and study quality was assessed with the Cochrane Risk of Bias Tool.</p><p><strong>Results: </strong>The analysis included 10 RCTs with 6,030 patients. Pembrolizumab combined with chemotherapy demonstrated a significant improvement in overall survival (OS: HR 0.80, 95% CI 0.65-0.97, P=0.02, I 2 =72.2%) and progression-free survival (PFS: HR 0.73, 95% CI 0.56-0.95, P=0.01, I2 =81.3%) compared to chemotherapy alone. Benefits in OS and PFS were also observed in subgroups with PD-L1 CPS ≥1 and CPS ≥10. In contrast, pembrolizumab monotherapy did not significantly improve OS (HR 0.99, 95% CI 0.88-1.12, P=0.89, I2 =0%) and was associated with shorter PFS (HR 1.51, 95% CI 1.34-1.71, P<0.001, I2 =0%). The combination therapy also resulted in higher complete and objective response rates.</p><p><strong>Discussion: </strong>This systematic review and meta-analysis provide comprehensive evidence regarding the efficacy and safety of pembrolizumab as monotherapy and in combination with chemotherapy for advanced GC/GEJC. Pooled analysis indicates that combination therapy yields significant survival benefits, particularly in patients with elevated PD-L1 expression. Conversely, monotherapy demonstrated no overall survival advantage and was associated with inferior progression-free survival compared to chemotherapy alone.</p><p><strong>Conclusion: </strong>Pembrolizumab combined with chemotherapy is an effective therapeutic strategy for advanced GC/GEJC, whereas monotherapy lacks superior efficacy in the general population and should be interpreted with caution due to observed heterogeneity.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343738","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":"Disrupting Redox Balance: A Redox-Based Strategy to Combat Temozolomide Resistance in Glioblastoma.","authors":"Asuman Celebi, Turker Kilic, Timucin Avsar","doi":"10.2174/0118715206470620260527200257","DOIUrl":"10.2174/0118715206470620260527200257","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma is an aggressive brain tumor with a median survival of only 15 months despite current therapies. Temozolomide (TMZ) is the standard chemotherapeutic due to its ability to cross the blood-brain barrier; however, acquired resistance limits its efficacy. Oxidative stress, particularly the regulation of Reactive Oxygen Species (ROS), has a dual role in tumor progression and cell death. Cancer cells tightly balance ROS through antioxidant systems fueled by NADPH, which is generated by NADK enzymes, while NADPH oxidases (NOX) produce ROS. Here, the study investigated whether disrupting NADPH homeostasis could enhance oxidative stress and induce cytotoxicity in TMZ-resistant glioblastoma.</p><p><strong>Materials and methods: </strong>The study investigated the effects of Thionicotinamide (TIO) and Sanguinarine (SNG), a NADK2 inhibitor and a NOX5 activator, on cell viability, gene expression, ROS and NADPH levels, apoptosis, and colony formation in glioma cell lines and healthy control HUVECs. Cells were treated for 24 hours with sub-toxic concentrations of SNG (0.5 µM) and TIO (100 µM).</p><p><strong>Results: </strong>Combined SNG and TIO treatment significantly reduced viability in TMZ-resistant cells (LN18 and TMZresU87-MG), but not in TMZ-sensitive or control cells. Intracellular ROS levels doubled in resistant cells after combined treatment, while NADPH levels decreased 20% in both resistant and sensitive glioma cells. Gene expression analysis revealed that TIO reduced NADK2 expression, and SNG upregulated NOX5 in TMZresistant cells.</p><p><strong>Discussion: </strong>These findings suggest that lowering NADPH levels (a necessary catalyst for the cell) and increasing ROS disrupted the cellular homeostasis. Increased oxidative stress in the cell is particularly pronounced in TMZ-resistant cells.</p><p><strong>Conclusion: </strong>This study provides evidence that co-targeting ROS production and NADPH depletion using SNG and TIO synergistically induces oxidative stress and cytotoxicity in TMZ-resistant glioma, highlighting a promising strategy for overcoming TMZ resistance.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306624","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":"Targeting Ceramide Metabolism to Overcome Osimertinib Resistance in EGFR-mutant Non-Small Cell Lung Cancer: An In Vitro, Network Pharmacology, and In Silico Study.","authors":"Oğuzhan Selvi, Canan Vejselova Sezer, Mustafa Cengiz, Nazlıhan Aztopal, Hatice Mehtap Kutlu","doi":"10.2174/0118715206475538260608072813","DOIUrl":"https://doi.org/10.2174/0118715206475538260608072813","url":null,"abstract":"<p><strong>Introduction: </strong>Osimertinib, an irreversible epidermal growth factor receptor inhibitor, is recognized for use in non-small cell lung cancer patients with the T790M resistance mutation. Though osimertinib offers a valuable advantage in survival of the patients, the occurrence of acquired resistance mechanisms confines the long-term efficacy of the therapy. Subsequently, evaluating the resistance mechanisms and generating alternative cure approaches are vital for improving therapeutic efficacy in advanced NSCLC. Herein, the aim was to research the effectiveness of inhibitors of acid ceramidases as promising alternative agents on targeting resistance- related cellular susceptibilities in osimertinib-sensitive (H1975/OS) and osimertinib-resistant (H1975/OR) NSCLC cells maintained under long-term exposure to osimertinib.</p><p><strong>Materials and methods: </strong>The cells were exposed to carmofur and B13 for 24, 48, and 72 hours. Antiproliferative and cytotoxic effects were investigated using the sulforhodamine B assay, and half-maximal growth inhibition (GI50), Total Growth Inhibition (TGI), and half-maximal Lethal Concentration (LC50) concentrations were detected. Proapoptotic activity was investigated using annexin V and caspase 3/7 techniques on a cell analyzer. The morphological alterations were investigated using confocal microscopy.</p><p><strong>Results: </strong>The analysis results indicated a proapoptotic effect in both cell lines for carmofur and B13. Carmofur exerted moderate cytotoxicity at all concentrations, while B13 showed weak efficacy at the tested high agent concentrations. Remarkably, the resistant cells remained sensitive to carmofur and B13, indicating that ceramide metabolism may be effective in a therapeutic setting in resistant NSCLC.</p><p><strong>Discussion: </strong>The results offer strong support for further mechanistic and translational investigation.</p><p><strong>Conclusion: </strong>The results suggest that carmofur and B13 are promising alternatives for therapeutic targets in drug-resistant lung cancer cells.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300346","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":"Near-Infrared Theranostics: Cutting-Edge Innovations in Cancer Diagnosis and Therapy.","authors":"Kritika, Amar Deep Ankalgi, Nikhil Sharma, Ankit Sharma, Mahendra Singh Ashawat, Aditi Kaushik","doi":"10.2174/0118715206405092251106142314","DOIUrl":"https://doi.org/10.2174/0118715206405092251106142314","url":null,"abstract":"<p><strong>Introduction: </strong>Theranostics of near-infrared (NIR) imaging, which originated from the merging of diagnostic imaging and targeted therapy, is one of the most remarkable achievements in the early diagnosis and treatment of malignancies. The NIR is divided into two optical windows: the first NIR I (700-900 nm) and the second NIR II (1000-1700 nm), which enable improved tissue penetration, reduced autofluorescence, and higher resolution compared with visible light.</p><p><strong>Methods: </strong>A literature search was conducted across databases, including PubMed, ScienceDirect, and the Cochrane Library. Eligibility criteria were randomized controlled trials (RCTs), preclinical/clinical studies, systematic reviews, and meta-analyses about NIR-related diagnosis and treatment modalities in oncology. Data extraction and synthesis focused on optical window properties (NIR-I and NIR-II), mechanisms of action, nanomaterial platforms, types of cancer treated, and clinical results.</p><p><strong>Results: </strong>NIR theranostic probes, including GBNPs, carbon nanotubes, and conjugated polymers, were found to possess good PTA and ROS generation capability, thus improving the therapeutic efficacy of PTTs and PDTs. NIR photoimmunotherapy (NIR-PIT) promoted ICD and enhanced CD8+ T cell-mediated tumor attack. NIR-II probes enabled deeper tissue penetration, allowing high tumor-to-background contrast imaging. Clinical trials in brain, breast, prostate, lung, and ovarian cancer revealed improved intraoperative guidance, tumor detection, and treatment.</p><p><strong>Discussion: </strong>Incorporation of NIR imaging into therapeutic nanoplatforms enables real-time, image-guided interventions, thereby improving treatment accuracy and minimizing systemic toxicity. However, regulatory approval, probe biocompatibility, and clinical scalability remain outstanding challenges.</p><p><strong>Conclusion: </strong>NIR theranostics represent a new arena for precision oncology. Future directions involve biocompatible, degradable/activatable NIR-II probes and multimodal systems complemented by AI-guided imaging for clinical translation and personalized cancer therapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300406","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":"Extracellular Vesicles and Their Multifaceted Roles in Cancer: Current Evidence from a Narrative Review.","authors":"Himanshu Singh, Ranjeet Kumar Yadav, Anmol Dogra","doi":"10.2174/0118715206434074260407093116","DOIUrl":"https://doi.org/10.2174/0118715206434074260407093116","url":null,"abstract":"<p><strong>Introduction: </strong>Extracellular Vesicles (EVs), including exosomes and microvesicles, are nanoscale, lipid bilayer-enclosed particles released by diverse cell types. They play a key role in intercellular communication by transferring proteins, lipids, and nucleic acids. In cancer, EVs contribute to remodelling the tumor microenvironment, enhancing angiogenesis, modulating immune responses, promoting metastasis, and driving therapeutic resistance.</p><p><strong>Aim: </strong>This narrative review aims to highlight the biological importance and clinical relevance of EVs in cancer, focusing on their potential as biomarkers and therapeutic tools.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science. Studies on EV composition, isolation, and characterization methods, as well as recent advances in EV bioengineering, were critically examined to summarize their significance in oncology.</p><p><strong>Results and discussion: </strong>Findings reveal that the molecular cargo of EVs reflects the physiological and pathological states of their source cells, supporting their role as non-invasive biomarkers for cancer detection and monitoring. EVs also regulate signaling pathways that sustain tumor heterogeneity and adaptability. Moreover, engineered EVs demonstrate strong potential as delivery systems for chemotherapeutic agents, RNA-based drugs, and immunomodulators, underscoring their translational value in targeted therapy.</p><p><strong>Conclusion: </strong>EVs represent versatile tools in precision oncology. Although standardization and clinical validation remain challenges, ongoing research and technological progress may establish EV-based strategies as integral components of personalized cancer treatment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275714","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":"Evaluation of the Effects of Bryonia multiflora Extract in a Chemically Induced Rat Breast Cancer Model.","authors":"Özgür Aslan, Ayhan Yıldırım, Mehmet Hanifi Durak","doi":"10.2174/0118715206476039260531171134","DOIUrl":"https://doi.org/10.2174/0118715206476039260531171134","url":null,"abstract":"<p><strong>Introduction: </strong>To evaluate the effects of dietary Bryonia multiflora Boiss. & Heldr. (B. multiflora) Extract, a rat breast cancer model was used that had been induced chemically with 7,12-dimethylbenz[a]anthracene (DMBA). In the study, haematological parameters, apoptosis markers (Bcl-2, Bax), and the protooncogene Her2 were evaluated.</p><p><strong>Methods: </strong>The study involved 47 female Wistar albino rats, aged 12 -14 weeks. Seven rats were selected for the control group and ten rats for each of the tumour and three application groups.</p><p><strong>Results: </strong>Statistically significant differences were found in terms of Bax between some pairs of groups. According to the Kruskal-Wallis results, statistically significant differences were found for Bax, MCV, MCH, MPV, and PDW (p < 0.05). However, the post-hoc Tamhane test revealed no significant differences between any of the groups (p > 0.05). Her-2 expression was detected in five rats (71.4%) in the control group and only in five rats (17.9%) in the tumour and plant extract groups.</p><p><strong>Conclusion: </strong>Bax expression levels were lower in the tumour group and the B. multiflora extract-treated groups than in the control group. The absence of the apoptotic and/or cytotoxic effects observed in previous studies involving Bryonia species in this study may be due to several factors. Similar studies should be conducted in the future to further understand the various therapeutic effects of plants.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270171","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":"Ferritin-Based Nanomedicine: A New Frontier in Cancer Therapy.","authors":"Rama Sharma","doi":"10.2174/0118715206437452260513105545","DOIUrl":"https://doi.org/10.2174/0118715206437452260513105545","url":null,"abstract":"<p><strong>Objectives: </strong>The study aims to examine the structural features, functional capabilities, and therapeutic applications of ferritin nanocages in treating cancer, emphasizing their potential as multifunctional platforms for the delivery of combined chemotherapy and phototherapy.</p><p><strong>Methods: </strong>An extensive literature review was conducted, investigating the biochemical characteristics of ferritin, its pH-responsive assembly and disassembly, along with its structural properties critical for drug encapsulation and targeting. Additionally, the review investigated modifications made to the ferritin surface to improve tumorspecific delivery, assessed various drug loading techniques, and analyzed reported applications in preclinical cancer therapies.</p><p><strong>Results: </strong>Ferritin nanocages, made up of 24 subunits that form a hollow center, inherently target tumors through recognition of transferrin receptor 1 (TfR1). Their benefits include excellent biocompatibility, low toxicity, low immunogenicity, remarkable stability (up to approximately 300°C), scalable production methods, and surfaces that can be modified for ligand or drug attachment.</p><p><strong>Discussion: </strong>The above results allow for the encapsulation of numerous therapeutic agents and imaging compounds, making ferritin a versatile platform for multimodal treatments. Ferritin-based systems have shown promise in targeted chemotherapy, phototherapy, and combination therapies, leading to enhanced therapeutic efficacy and protection of the cargo.</p><p><strong>Conclusion: </strong>Ferritin is a promising natural nanoplatform for targeted drug delivery to tumors and multimodal cancer treatment. Its dual functions in cancer development and therapeutic action, along with its structural flexibility, enhance its potential to improve cancer therapy. Nevertheless, barriers to clinical application persist, requiring further optimization and validation in clinical environments.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262892","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":"7MeERT Enhances Antibody-Drug Conjugate Efficacy in Glioblastoma by Inducing AMPK-p38MAPK-Mediated Non-Canonical Endocytosis of EGFRvIII.","authors":"Sonoko Atsumi, Chisato Nosaka, Takefumi Onodera, Masabumi Shibuya, Se In Park, Ho Jeong Kwon, Hiroaki Sakurai, Manabu Kawada","doi":"10.2174/0118715206419446251003053611","DOIUrl":"https://doi.org/10.2174/0118715206419446251003053611","url":null,"abstract":"<p><strong>Introduction: </strong>Antibody-drug conjugates (ADCs) targeting EGFR variant III (EGFRvIII) hold promise for glioblastoma therapy, but clinical efficacy is limited by poor receptor internalization.</p><p><strong>Methods: </strong>We evaluated the effects of 7MeERT, a quinoline derivative, on EGFRvIII internalization and the activity of Depatuxizumab Mafodotin (ABT-414) in glioblastoma cells. Western blotting, immunofluorescence, Seahorse assays, and RNA interference were employed to dissect the involved signaling pathways.</p><p><strong>Results: </strong>7MeERT reduced intracellular ATP levels and activated AMPKα1, which subsequently triggered p38MAPK phosphorylation. This cascade led to the phosphorylation of serine 1015 on EGFRvIII and promoted its internalization via non-canonical endocytosis. The internalization of both EGFRvIII and ABT-414 was confirmed in glioblastoma cells and was shown to be dependent on AMPKα1-p38MAPK. 7MeERT treatment enhanced the cytotoxic efficacy of ABT-414 in EGFRvIII-expressing cells but had no effect in EGFRvIII-negative cells.</p><p><strong>Discussion: </strong>Our findings demonstrate a metabolic mechanism by which 7MeERT promotes non-canonical endocytosis of EGFRvIII, enhancing ADC uptake. The AMPK-p38MAPK-EGFRvIII axis plays a central role in this process.</p><p><strong>Conclusion: </strong>7MeERT enhances EGFRvIII-targeting ADC efficacy in glioblastoma by inducing metabolic stress and triggering AMPK-p38MAPK-mediated non-canonical endocytosis. This strategy may improve ADC delivery in tumors with impaired receptor internalization.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257112","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}