Anti-cancer Agents In Medicinal Chemistry[JOURNAL]
Sun
200 papers
Emerging Frontiers in Nanomedicine for Colorectal Cancer: A Review of Therapeutic Advances, Clinical Evidence, and Patented Technologies.
Dushyant, Narwal S, Singh G … +4 more , Dhingra AK, Kaur J, Balram, Grewal N
Anticancer Agents Med Chem · 2026 Jul · PMID 42393892 · Publisher ↗
INTRODUCTION: Colorectal cancer (CRC) is the third most prevalent cancer globally, and metastatic CRC is almost always fatal. Early stages (0 to III) of CRC are generally curable, but Stage IV CRC is typically not curabl...
INTRODUCTION: Colorectal cancer (CRC) is the third most prevalent cancer globally, and metastatic CRC is almost always fatal. Early stages (0 to III) of CRC are generally curable, but Stage IV CRC is typically not curable and can only be controlled depending on the extent of disease spread. The objective of the current study is to discuss efficient targeted drug delivery systems for CRC and critically assess recent advancements in nanotechnology-based drug delivery. METHODS: A critical review of the literature was conducted, including patent and clinical trial analyses on nanotechnology-based drug delivery systems for CRC. The research aimed to evaluate new nanocarriers such as dendrimers, liposomes, carbon nanotubes, and nanoemulsions. RESULTS: Nanotechnology-based novel drug delivery systems were identified as more specific for targeting CRC cells. These technologies have been shown to exhibit greater cellular uptake, improved pharmacokinetics, and enhanced overall efficacy of anticancer drugs. Evidence from clinical trials and patent statistics reaffirms the potential of nanomedicines to revolutionize CRC therapy by increasing drug specificity and reducing systemic toxicity. DISCUSSION: The findings indicate the enormous potential of nanotechnology to improve CRC therapy through better drug targeting and fewer side effects. The results are consistent with the growing body of literature supporting the integration of nanocarriers into oncology. Despite challenges such as the need for validation in clinical settings and the translation of laboratory successes into conventional medical practice, continued efforts are essential to make effective cancer treatment a reality without causing harm. CONCLUSION: Nanotechnology-based drug delivery systems have significant therapeutic potential in the management of CRC by maximizing treatment efficacy and minimizing side effects. Additional research and clinical data are needed to establish these systems as an integral part of routine clinical practice.
Microfluidic Synthesis of miR-10a Antisense Oligonucleotides-Loaded LNP Combined with Cisplatin for Colorectal Cancer Therapy.
Li S, Li J, Jiang H … +4 more , Zhao K, Luo L, Huang H, Liang Z
Anticancer Agents Med Chem · 2026 Jul · PMID 42393891 · Publisher ↗
INTRODUCTION: To address the issue of insufficient sensitivity of the chemotherapeutic drug cisplatin in colorectal cancer (CRC), this study aimed to develop a miR-10a antisense oligonucleotide (AMO) system delivered by...
INTRODUCTION: To address the issue of insufficient sensitivity of the chemotherapeutic drug cisplatin in colorectal cancer (CRC), this study aimed to develop a miR-10a antisense oligonucleotide (AMO) system delivered by lipid nanoparticles (LNPs). The aim was to enhance the sensitivity and efficacy of cisplatin by targeting and inhibiting the expression of miR-10a in CRC. METHODS: Through bioinformatics analysis, key miRNAs that are differentially expressed in colon cancer were identified. Then, by using the FDA-approved patisiran formulation and microfluidic technology, LNPs/miR10a- AMOs were constructed to target miR-10a. The transfection efficiency, anti-tumor effectiveness, and safety were evaluated through in vivo and in vitro experiments. RESULTS: LNPs increased the transfection efficiency of AMOs by 2.3 times (p < 0.01). In HCT116 cells, miR- 10a expression was inhibited by 68.5%, and after combined treatment with cisplatin, the IC50 decreased from 8.7 μM to 5.0 μM (p < 0.001). Meanwhile, cell viability in normal THLE2 and HCoEpiC cells remained > 85%. In the xenograft model, the combined therapy achieved a 100.4% tumor growth inhibition compared to cisplatin monotherapy, with Ki67 expression decreased by 67.3%, and cleaved-caspase-3 expression increased by 3.1- fold (p<0.001). Histopathological analysis confirmed minimal organ toxicity. Mechanistically, miR-10a downregulation sensitized the tumor by activating the apoptotic pathway and inhibiting proliferation. DISCUSSION: Our findings demonstrated that targeting miR-10a significantly enhanced the sensitivity of tumor cells to cisplatin, providing a novel strategic approach to overcome chemoresistance. Compared to existing studies, the innovation of this work lies in employing an FDA-approved LNP formulation, substantially improving the feasibility for clinical translation. Furthermore, the application of microfluidic technology ensured reproducible nanoparticle preparation, offering distinct advantages over conventional methods in terms of industrial applicability. However, this study has involved certain limitations; the animal models utilized could not fully recapitulate the complexity of the human tumor microenvironment, and the precise molecular mechanisms regulated by miR-10a warrant further investigation. CONCLUSION: LNPs/miR-10a-AMOs can efficiently deliver AMOs and represent a potential strategy for treating CRC. By enhancing the sensitivity of tumors to cisplatin, this system improved the therapeutic effect while ensuring the safety of normal cells. This provides a new strategy with translational potential for the precise treatment of CRC.
Synergistic Anticancer Effect of Luteolin and Etoposide via the PI3K/AKT Signaling Pathway.
Huang W, Liang F, Xu H … +3 more , Zhang R, Zhao M, Sun T
Anticancer Agents Med Chem · 2026 Jun · PMID 42381145 · Publisher ↗
BACKGROUND: Etoposide (VP-16) is a widely used chemotherapeutic agent, but its efficacy is limited by toxicity and resistance. Luteolin (LUT), a natural flavonoid, exhibits antitumor activity and may enhance chemotherapy...
BACKGROUND: Etoposide (VP-16) is a widely used chemotherapeutic agent, but its efficacy is limited by toxicity and resistance. Luteolin (LUT), a natural flavonoid, exhibits antitumor activity and may enhance chemotherapy through signaling modulation. This study explores the synergistic effects of LUT and VP-16 and the underlying mechanism. METHODS: The H22 and 4T1 mouse tumor cells, as well as the human hepatocellular carcinoma cell line Huh7, were treated with LUT, VP-16, or their combination. The cell viability, colony formation, and apoptosis were evaluated by CCK-8 assay, crystal violet staining, and TUNEL assay, and the synergistic effect was analyzed using the combination index. The involvement of the PI3K/AKT signaling pathway was detected by Western blotting, and the agonist rescue experiment was conducted for verification. Antitumor efficacy and systemic toxicity were further evaluated in a subcutaneous xenograft mouse model. RESULTS: LUT and VP-16 combination significantly inhibited proliferation and clonogenic potential while promoting apoptosis in all tested cell lines (P < 0.01). Western blotting showed suppression of PI3K and AKT phosphorylation, effects reversed by 740 Y-P. In vivo, the combination produced the strongest tumor reduction with enhanced apoptosis and reduced PI3K/AKT activation. DISCUSSION: The synergistic effect of LUT and VP-16 is largely mediated by PI3K/AKT pathway inhibition, providing mechanistic insight into their combined antitumor action and suggesting a strategy to enhance chemotherapy efficacy. CONCLUSION: LUT enhances the antitumor efficacy of VP-16 by synergistically inhibiting the PI3K/AKT signaling pathway. This combination presents a promising therapeutic strategy for improving chemotherapy outcomes in solid tumors.
Targeting Eg5 with K858: A Strategy for Radiosensitization Through ROS-Mediated DNA Damage in Esophageal Squamous Cell Carcinoma.
Liu R, Zhou S, Xiao F … +3 more , Chen M, Xu X, Liu X
Anticancer Agents Med Chem · 2026 Jun · PMID 42381144 · Publisher ↗
INTRODUCTION: Radiotherapy resistance poses a major challenge in the treatment of esophageal squamous cell carcinoma (ESCC). The kinesin Eg5 is overexpressed in human cancers and has emerged as a candidate therapeutic ta...
INTRODUCTION: Radiotherapy resistance poses a major challenge in the treatment of esophageal squamous cell carcinoma (ESCC). The kinesin Eg5 is overexpressed in human cancers and has emerged as a candidate therapeutic target. The Eg5 inhibitor K858 cooperates with radiotherapy to block ESCC progression, but whether this synergy stems from modulation of irradiation-induced reactive oxygen species (ROS) and DNA damage is unknown. We aimed to establish the clinical significance of Eg5 in ESCC, and to investigate whether pharmacological Eg5 inhibition by K858 enhances radiosensitivity via ROS-mediated DNA damage. METHODS: We employed bioinformatic interrogation of public databases, retrospective analysis of an institutional patient cohort (n = 30) with immunohistochemistry validation, and in vitro studies using ESCC cell lines. We assessed correlations between Eg5 expression levels, clinicopathological features, and patient survival. ROS generation was measured by flow cytometry, and γH2AX foci detection by immunofluorescence following K858 and radiotherapy treatment. RESULTS: Eg5 mRNA and protein levels were highly upregulated across ESCC and various cancers compared to normal tissues. Eg5 expression correlated with smoking history, poorer histological grade, and reduced overall survival in our patient cohort. Furthermore, a negative correlation between Eg5 expression and E-cadherin status identified Eg5 as a regulator of epithelial-mesenchymal transition. Mechanistically, K858 treatment enhanced ROS generation and increased γH2AX foci accumulation induced by radiotherapy, indicating that inhibition of Eg5 promotes radiotherapy efficacy through oxidative DNA injury. DISCUSSION: These data support the combination of K858, an Eg5-targeting compound, and radiotherapy as a strategy for treating ESCC by enhancing oxidative stress and unresolved DNA lesions. Our results suggest that kinesin Eg5 may be utilized not only as a prognostic biomarker but also as a bona fide target for overcoming radioresistance. CONCLUSION: Eg5 represents not only an independent prognostic marker but also a promising drug target for ESCC, yet the findings still need to be validated in large-scale prospective studies. Inhibiting this kinesin protein with K858 may represent a novel therapeutic strategy to sensitize ESCC to radiotherapy.
Pulsatilla chinensis Saponins as Multitargeted Anticancer Agents: A Mini-Review of Molecular Mechanisms and Therapeutic Potential.
Sun J, Nie F, Sun X … +1 more , Wang Y
Anticancer Agents Med Chem · 2026 Jun · PMID 42367129 · Publisher ↗
INTRODUCTION: 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 Sapon...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: Pulsatilla saponins represent promising multi-target anticancer candidates. Future studies should focus on improving their pharmacokinetic properties and delivery systems to facilitate clinical translation.
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.
Bai Z, Ding Z, Yang S … +4 more , Du K, Deng L, Qian Y, Li H
Anticancer Agents Med Chem · 2026 Jun · PMID 42367128 · Publisher ↗
INTRODUCTION: 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 C...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
Discovery of Serum Exosomal Protein Biomarkers for Early- and Late-Stage Lung Cancer Through Comparative Proteomic Analysis.
Zeng D, Huang X, Tang H … +4 more , Chen M, Xu J, Shi Y, Song S
Anticancer Agents Med Chem · 2026 Jun · PMID 42367127 · Publisher ↗
BACKGROUND: 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...
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
Disrupting Redox Balance: A Redox-Based Strategy to Combat Temozolomide Resistance in Glioblastoma.
Celebi A, Kilic T, Avsar T
Anticancer Agents Med Chem · 2026 Jun · PMID 42337877 · Publisher ↗
INTRODUCTION: 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...
INTRODUCTION: 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. MATERIALS AND METHODS: 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). RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
Targeting Ceramide Metabolism to Overcome Osimertinib Resistance in EGFR-mutant Non-Small Cell Lung Cancer: An In Vitro, Network Pharmacology, and In Silico Study.
Selvi O, Sezer CV, Cengiz M … +2 more , Aztopal N, Kutlu HM
Anticancer Agents Med Chem · 2026 Jun · PMID 42333846 · Publisher ↗
INTRODUCTION: 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...
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. DISCUSSION: The results offer strong support for further mechanistic and translational investigation. CONCLUSION: The results suggest that carmofur and B13 are promising alternatives for therapeutic targets in drug-resistant lung cancer cells.
Near-Infrared Theranostics: Cutting-Edge Innovations in Cancer Diagnosis and Therapy.
Kritika, Ankalgi AD, Sharma N … +3 more , Sharma A, Ashawat MS, Kaushik A
Anticancer Agents Med Chem · 2026 Jun · PMID 42333552 · Publisher ↗
INTRODUCTION: 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...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
Extracellular Vesicles and Their Multifaceted Roles in Cancer: Current Evidence from a Narrative Review.
Singh H, Yadav RK, Dogra A
Anticancer Agents Med Chem · 2026 Jun · PMID 42316572 · Publisher ↗
INTRODUCTION: 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 tra...
INTRODUCTION: 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. AIM: 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. METHODS: 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. RESULTS AND DISCUSSION: 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. CONCLUSION: 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.
Evaluation of the Effects of Bryonia multiflora Extract in a Chemically Induced Rat Breast Cancer Model.
Aslan Ö, Yıldırım A, Durak MH
Anticancer Agents Med Chem · 2026 Jun · PMID 42312524 · Publisher ↗
INTRODUCTION: 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)....
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Ferritin-Based Nanomedicine: A New Frontier in Cancer Therapy.
Sharma R
Anticancer Agents Med Chem · 2026 Jun · PMID 42304904 · Publisher ↗
OBJECTIVES: 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...
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
7MeERT Enhances Antibody-Drug Conjugate Efficacy in Glioblastoma by Inducing AMPK-p38MAPK-Mediated Non-Canonical Endocytosis of EGFRvIII.
Atsumi S, Nosaka C, Onodera T … +5 more , Shibuya M, Park SI, Kwon HJ, Sakurai H, Kawada M
Anticancer Agents Med Chem · 2026 Jun · PMID 42300319 · Publisher ↗
INTRODUCTION: Antibody-drug conjugates (ADCs) targeting EGFR variant III (EGFRvIII) hold promise for glioblastoma therapy, but clinical efficacy is limited by poor receptor internalization. METHODS: We evaluated the effe...
INTRODUCTION: Antibody-drug conjugates (ADCs) targeting EGFR variant III (EGFRvIII) hold promise for glioblastoma therapy, but clinical efficacy is limited by poor receptor internalization. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
Exploring the Therapeutic Potential of an Iron(III)-Polysaccharide Complex Derived from Hypsizygus ulmarius.
Govindan S, Nagarajan A, Sukumaran A … +1 more , Ramani P
Anticancer Agents Med Chem · 2026 Jun · PMID 42300318 · Publisher ↗
INTRODUCTION: This current research involves the synthesis and biological evaluation of an iron complex derived from the Hypsizygus ulmarius polysaccharide (HUP-Fe(III)), with the aim of determining its potential as an i...
INTRODUCTION: This current research involves the synthesis and biological evaluation of an iron complex derived from the Hypsizygus ulmarius polysaccharide (HUP-Fe(III)), with the aim of determining its potential as an iron supplement and a bioactive agent. METHODS: HUP-Fe(III) was characterized using FT-IR, NMR, SEM, XRD, molecular weight analysis, and monosaccharide profiling. Antioxidant capacity was assessed by DPPH, ABTS, hydroxyl radical scavenging, and ferric/cupric ion reduction assays. Antibacterial activity was tested against Gram-positive and Gram-negative strains. Anti-inflammatory effects were evaluated through membrane stabilization and hemolysis inhibition. Coagulation parameters such as Activated Partial Thromboplastin Time (APTT), Thrombin Time (TT), and Prothrombin Time (PT) were measured, and anticancer activity against Triple-Negative Breast Cancer (TNBC) cell lines was analyzed, including effects on cell cycle progression and mitochondrial function. RESULTS: The analysis of HUP-Fe(III) revealed an iron content of 7.56%, and SEM and XRD investigations showed significant morphological changes and reduced crystallinity after Fe³⁺ chelation. FT-IR and XRD patterns point to a β-FeOOH structure, while NMR evidence indicates changes in glycosidic connections in the anomeric region. The anti-oxidant results indicated that HUP-Fe(III) had better radical scavenging activity than native HUP. Antibacterial analysis showed moderate-to-high inhibition. In vitro anti-inflammatory experiments showed that HUP-Fe(III) improved membrane stability and hemolysis prevention. The APTT and TT were significantly prolonged, while PT was unaffected. HUP-Fe(III) strongly inhibited TNBC cell lines by arresting G2/M cell cycle and causing mitochondrial malfunction. These findings indicate that HUP-Fe(III) exhibits promising multifunctional biological activities, suggesting its potential for further investigation as a candidate for iron supplementation. DISCUSSION: Polysaccharide-iron complexes enhanced surface charge may enhance their ability to interact with microbial surfaces and boost their antibacterial activity, especially against Gram-negative bacteria. The HUPFe( III) can improve the protective effects against hemolysis by stabilizing the membrane more effectively, perhaps as a result of iron coordinating with membrane lipids. The HUP-Fe(III) may exert a stronger or prolonged effect on the intrinsic coagulation pathway, potentially through enhanced interaction with clotting factors. The complex exerted enhanced antitumor activity against TNBC cells by reducing viability, inducing cell cycle arrest at the G2/M phase, and collapsing mitochondrial membrane potential, likely through ROS-mediated apoptosis. CONCLUSION: HUP-Fe(III) is a safe, multifunctional candidate for incorporation into functional foods or therapeutics addressing iron deficiency and oxidative stress-related disorders.
A Meta-Analysis and Systematic Review of the Frequency, Clinicopathological Features, and Diagnostic Potential of CDH1 Methylation in Head and Neck Cancer.
Alqahtani M, Alzuhairi AM, Alalmaie OH … +12 more , Alahmari FN, Alahmari MN, Alanazi MA, Alziyad YA, Alqahtani MH, Alshahrani NA, Alawdah HA, Alqarni AA, Bin Libdah FM, Salem Aldanyowi SN, Yaseen Albar N, Aleid AM
Anticancer Agents Med Chem · 2026 Jun · PMID 42300317 · Publisher ↗
INTRODUCTION: Head and neck cancer (HNC), particularly head and neck squamous cell carcinoma (HNSCC), is a major global health issue. Epigenetic alterations, especially the hypermethylation of tumor suppressor genes (TSG...
INTRODUCTION: Head and neck cancer (HNC), particularly head and neck squamous cell carcinoma (HNSCC), is a major global health issue. Epigenetic alterations, especially the hypermethylation of tumor suppressor genes (TSGs) such as CDH1, which encodes the E-cadherin protein, play a crucial role in the development and progression of HNC. This meta-analysis aimed to evaluate the role of CDH1 methylation as a potential diagnostic and less invasive biomarker for HNC, assessing its correlation with various clinical, pathological, and lifestyle factors, including tumor size, lymph node involvement, clinical stage, smoking, and alcohol consumption. METHODS: A systematic search was conducted across multiple databases (PubMed, Scopus, Web of Science, and Cochrane Library) up to September 2024. Studies that reported the frequency of CDH1 methylation in HNC patients and its association with clinicopathological factors were included. Statistical analysis was performed using Review Manager (RevMan 5.4) software, and diagnostic test accuracy (DTA) was assessed through sensitivity, specificity, and area under the curve (AUC) analyses using MetaDesk software. RESULTS: Forty-three studies, involving 1542 HNC patients and 1532 controls, were included. The pooled analysis showed a significantly higher prevalence of CDH1 methylation in HNC patients compared to controls (OR = 8.09, 95% CI: 5.29-12.36, P < 0.001). Subgroup analysis revealed significant associations in both Asian and Caucasian populations and various tumor subtypes. CDH1 methylation correlated with alcohol consumption and advanced clinical stage, but not with tumor size, lymph node involvement, or metastatic status. The pooled diagnostic odds ratio was 8.18 (95% CI: 5.32-12.58), with an AUC of 0.78, indicating moderate diagnostic accuracy. CONCLUSION: CDH1 methylation holds promise as a diagnostic biomarker for HNC, demonstrating high specificity but moderate sensitivity. While its association with specific clinicopathological factors is notable, it should be used in conjunction with other diagnostic tools for more effective clinical application.
Recent Advances in Intravesical Chemotherapy: Insights into the FDA-Approved Gemcitabine-Releasing TAR-200 System for Bladder Cancer Management.
Sharma A, Kumar A, Patel P … +1 more , Kurmi BD
Anticancer Agents Med Chem · 2026 Apr · PMID 42299000 · Publisher ↗
The FDA approval of the gemcitabine intravesical system (Inlexzo/TAR-200) marks a breakthrough for BCG-unresponsive NMIBC with CIS. This novel drug-device combination enables sustained intravesical chemotherapy, achievin...
The FDA approval of the gemcitabine intravesical system (Inlexzo/TAR-200) marks a breakthrough for BCG-unresponsive NMIBC with CIS. This novel drug-device combination enables sustained intravesical chemotherapy, achieving high complete response rates with acceptable safety. It represents a paradigm shift in bladder-sparing therapy, though long-term outcomes and accessibility remain critical considerations.
QSAR Modeling of Camptothecin Derivatives Targeting Topoisomerase I: Structural Insights for Anticancer Drug Design.
Mahmoud HA, Elnady NA, Elmallah SA
Anticancer Agents Med Chem · 2026 Jun · PMID 42283190 · Publisher ↗
INTRODUCTION: This study investigates the quantitative structure-activity relationship (QSAR) of camptothecin derivatives to determine how variations in their structures affect the activity of these derivatives on Topois...
INTRODUCTION: This study investigates the quantitative structure-activity relationship (QSAR) of camptothecin derivatives to determine how variations in their structures affect the activity of these derivatives on Topoisomerase I (Top I), a crucial enzyme involved in DNA replication in cancer cells. METHODS: A total of 55 camptothecin derivatives were divided into training and test sets, with biological activity (IC50) as the dependent variable. A Partial Least Squares (PLS) Regression model was developed using the calculated molecular descriptors to predict the IC50 values. RESULTS: The R² and Q² values were 0.99852 and 0.249, respectively. QSAR results indicate that molar refractivity, hydrophilicity, molecular weight, and the ether group count highly contribute to the expected activity of camptothecin (CPT) derivatives on Top I. CONCLUSION: This study presents a computational approach to better understand how the structure of camptothecin derivatives affects their activity against Topoisomerase I, which could inform the future design of more effective anticancer drugs.
Analysis of the Oncogenic Role of Colony-Stimulating Factor 1 Receptor (CSF1R) in Pancreatic Adenocarcinoma.
Cui H, Piao X, Zhang J … +2 more , Han Z, Xu Q
Anticancer Agents Med Chem · 2026 Jun · PMID 42283189 · Publisher ↗
INTRODUCTION: Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we profiled the role of Colony-Stimulating Factor 1 Receptor (CSF1R) in cancer. We specifically focused on pancreatic ductal adenoc...
INTRODUCTION: Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we profiled the role of Colony-Stimulating Factor 1 Receptor (CSF1R) in cancer. We specifically focused on pancreatic ductal adenocarcinoma (PAAD), analysing its regulative function in cancer progression and its usefulness as a potential biomarker and therapeutic target. METHODS: Using the TCGA and GEO databases, gene expression, survival prognosis, genetic abnormalities, immune infiltration, and CSF1R-related gene enrichment related to the CSF1R gene in patients with PAAD were studied. RESULTS: CSF1R expression appears to affect the development of PAAD; there is more CSF1R expression in the tumour tissue than in nearby normal tissues. There was no statistical difference in the overall survival or diseasefree survival of CSF1R expression. Analysis of changes in the CSF1R gene showed that PAAD samples had a low mutation frequency, and CSF1R gene amplification was the main reason. It was additionally emphasized that the impact of CSF1R on the tumor microenvironment, as evidenced by an immunological infiltration analysis, showed a strong correlation between the estimated infiltration values of cancer-associated fibroblasts and CSF1R expression in PAAD. This additional evidence was found for CSF1R expression in cancer-associated fibroblasts in PAAD. DISCUSSION: Targeting CSF1R might be a promising strategy for PAAD treatment. Inhibiting CSF1R activity or TGF-β binding to CSF1R inhibits tumour growth and immune escape. Investigating the link between CSF1R, TGF-β, and the immune system leads to new opportunities for combination therapies that integrate targeted medicine with immunotherapy. CONCLUSION: Targeting CSF1R might be a PAAD treatment. Inhibiting CSF1R activity or TGF-β binding to CSF1R inhibits tumour growth and immune escape. Investigating the link between CSF1R, TGF-β, and the immune system opens new opportunities for combining targeted medicines with immunotherapy.
Targeting CHCHD3 inhibits tumorigenesis of NSCLC by Reprogramming Mitochondrial Metabolism.
Jin L, Shen J, Xu X … +5 more , Niu P, Zhou Y, Dong S, Shen Q, Gu Q
Anticancer Agents Med Chem · 2026 Jun · PMID 42261148 · Publisher ↗
BACKGROUND: Mitochondria are essential organelles for cellular metabolism and tumor formation. We discovered that CHCHD3 is an important inner mitochondria membrane protein involved in the proliferation of lung adenocarc...
BACKGROUND: Mitochondria are essential organelles for cellular metabolism and tumor formation. We discovered that CHCHD3 is an important inner mitochondria membrane protein involved in the proliferation of lung adenocarcinoma (LUAD). However, the molecular pathways through which CHCHD3 contributes to cancer progression remain poorly understood. METHODS: Following CHCHD3 knockdown, cell proliferation was assessed by CCK8 assay, colony formation assay, and cell cycle analysis. Apoptosis, intracellular Reactive Oxygen Species (ROS) levels, and mitochondrial membrane potential were evaluated using flow cytometry, JC-1 staining, and Western blot analysis, respectively. Mitochondrial function was measured using a Seahorse analyzer. Immunoprecipitation coupled with mass spectrometry (IP-MS) and Co-immunoprecipitation (CO-IP) were used to identify CHCHD3-interacting proteins. RESULTS: CHCHD3 expression was significantly upregulated in lung cancer tissues, with its overexpression correlating with poor patient survival. In LUAD cells, CHCHD3 knockdown suppressed proliferation, induced G1 cell cycle arrest, and triggered cellular dysfunction, including apoptosis and mitochondrial energy metabolism impairment. IP-MS screening identified several potential CHCHD3-interacting proteins, among which SAMM50 and VDAC1/2 were validated as direct binding partners. Dysregulation of these interactions may underlie the excessive production of ROS observed upon CHCHD3 loss. DISCUSSION: Our results demonstrate that CHCHD3 is highly expressed in lung adenocarcinoma and positively correlates with poor prognosis. Mechanistically, CHCHD3 loss is associated with mitochondrial dysfunction, ROS accumulation, and activation of the intrinsic apoptotic pathway. CONCLUSION: Our study identifies CHCHD3 as a mitochondrial protein upregulated in lung cancer that contributes to tumor cell proliferation and survival.
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