Anti-cancer Agents In Medicinal Chemistry[JOURNAL]
Sun
200 papers
Unlocking the Potential of Polysaccharides for the Treatment of Lung Cancer.
Singh H, Kumar R, Mazumder A
Anticancer Agents Med Chem · 2025 Sep · PMID 40908690 · Publisher ↗
BACKGROUND: Lung cancer remains a leading cause of cancer-related deaths worldwide, with its incidence continuing to rise. Despite advancements in clinical treatments, their effectiveness is often restricted, emphasizing...
BACKGROUND: Lung cancer remains a leading cause of cancer-related deaths worldwide, with its incidence continuing to rise. Despite advancements in clinical treatments, their effectiveness is often restricted, emphasizing the need for novel therapeutic strategies. Natural products have long been explored for drug development, and among them, polysaccharides have gained significant attention due to their biocompatibility, biodegradability, and multiple biological functions. METHODS: A comprehensive review examined contemporary research on the anticancer properties of natural polysaccharides, focusing specifically on their effects in lung cancer. The analysis included studies investigating their influence on cancer cell growth, immune system modulation, and therapeutic outcomes. Evidence from laboratory (in vitro), animal (in vivo), and clinical studies was evaluated to provide a comprehensive overview of their potential role in lung cancer management. RESULTS: Findings from recent studies indicate that polysaccharides can effectively inhibit the proliferation of lung cancer cells, thereby slowing tumor development. These compounds also appear to enhance immune responses by activating various immune cells and regulating cytokine production. Furthermore, polysaccharides have been shown to positively affect the gut microbiota, which may contribute to improved drug efficacy and a reduction in resistance to chemotherapy. DISCUSSION: The evidence suggests that natural polysaccharides exert multifaceted effects in the context of lung cancer treatment. Their ability to directly suppress tumor growth, modulate the immune system, and interact with the gut microbiome positions them as promising adjuncts to existing therapies. However, the precise molecular mechanisms underlying these effects are not yet fully understood, and variability in study designs warrants cautious interpretation of the results. CONCLUSION: Natural polysaccharides represent a promising complementary approach for lung cancer therapy, given their potential to inhibit tumor progression, enhance immune function, and improve the effectiveness of conventional drugs. Continued research is essential to fully elucidate their mechanisms of action and to translate these findings into effective clinical interventions.
Long Non-Coding RNA VPS9D1-AS1 in Human Cancer: Functions, Mechanisms, and Clinical Utility.
Yang J, He H, Liu H … +4 more , Xu Z, Li L, Li H, Yuan C
Anticancer Agents Med Chem · 2026 · PMID 40908689 · Publisher ↗
INTRODUCTION: VPS9 domain-containing 1 antisense RNA 1 (VPS9D1-AS1), also known as c-Mycupregulated lncRNA (MYU) and FAK-interacting and stabilizing lncRNA (FAISL), is a novel long non-coding RNA (lncRNA) located at the...
INTRODUCTION: VPS9 domain-containing 1 antisense RNA 1 (VPS9D1-AS1), also known as c-Mycupregulated lncRNA (MYU) and FAK-interacting and stabilizing lncRNA (FAISL), is a novel long non-coding RNA (lncRNA) located at the human chromosome 16q24.3 locus. It has been reported to be highly expressed in various human cancers and associated with poor clinical pathological features and unfavorable prognosis in eight of the malignant tumors. METHODS: A comprehensive literature search was conducted using PubMed, Web of Science, and Google Scholar databases to identify relevant articles on "VPS9D1-AS1", "MYU", or "FAISL". Only peer-reviewed publications were included, and articles related to oncology were specifically collected. RESULTS: Mechanistically, VPS9D1-AS1 serves as a key regulator in four molecular models: signal, scaffold, guide, and decoy. These functions allow it to regulate the expression of target genes and activation of signaling pathways, thereby influencing the malignant phenotype of tumors. DISCUSSION: The diverse molecular mechanisms of VPS9D1-AS1 highlight its significant role in the development and progression of various cancers. Its ability to act as a signal, scaffold, guide, and decoy suggests that it can influence multiple aspects of tumor biology, including proliferation, invasion, and metastasis. CONCLUSION: VPS9D1-AS1 plays a significant role in the development and progression of various cancers through its diverse molecular mechanisms. Further research on VPS9D1-AS1 may provide valuable insights, which may facilitate the development of new diagnostic and therapeutic strategies for cancer.
Narrative Review Article A Comprehensive Review of the Anticancer Activity of Farnesiferol C and Umbelliferone.
Faghih R, Talebi-Esmaeilan M, Mohamadi-Zarch SM … +1 more , Bagheri SM
Anticancer Agents Med Chem · 2025 Sep · PMID 40908520 · Publisher ↗
Cancer remains a growing challenge in modern society, presenting a significant obstacle in both developed and developing countries. Conventional treatments are often costly and limited by issues such as drug resistance a...
Cancer remains a growing challenge in modern society, presenting a significant obstacle in both developed and developing countries. Conventional treatments are often costly and limited by issues such as drug resistance and undesirable side effects. Consequently, the exploration of natural compounds has emerged as a promising strategy for developing more effective and tolerable cancer therapies. Among these, Ferula plants have gained attention for their potential anticancer components. Notably, two coumarin compounds derived from these plants, farnesiferol C and umbelliferone, have demonstrated substantial anticancer activity, as supported by an increasing number of published studies. This review aims to consolidate existing evidence on the anticancer effects of farnesiferol C and umbelliferone while comparing their efficacy as potential therapeutic agents. To accomplish this, a comprehensive literature search was conducted using the terms "umbelliferone" and "farnesiferol C" paired with "anticancer" across databases such as ISI Web of Knowledge, PubMed, and Google Scholar. Relevant studies up to March 2024 were retrieved, summarized, and incorporated into this analysis. The findings indicate that both compounds exhibit significant anticancer properties, positioning them as viable candidates for future drug development. A comparative analysis of their IC50 values, the concentration required to inhibit 50% of cancer cell growth, reveals that farnesiferol C demonstrates greater cytotoxic potency against various cancer cell lines compared to umbelliferone. However, while these results are encouraging, further research is recommended, particularly in vivo studies to evaluate the compounds' toxicity and therapeutic potential in living organisms.
Ursolic Acid Inhibits Triple-Negative Breast Cancer Progression by Modulating the FGFR1/AKT/ERK Pathway: Evidence from Network Pharmacology and Experimental Validation.
Chen Z, Guo W, Gao Y … +6 more , Zhao P, Liu X, Qian M, You S, Wang X, Xiang M
Anticancer Agents Med Chem · 2025 Aug · PMID 40873180 · Publisher ↗
INTRODUCTION: Ursolic acid (UA) exhibits antitumor activity; however, its effects and mechanisms on triple-negative breast cancer (TNBC) cells are not well understood. The present study aimed to explore the anti- TNBC me...
INTRODUCTION: Ursolic acid (UA) exhibits antitumor activity; however, its effects and mechanisms on triple-negative breast cancer (TNBC) cells are not well understood. The present study aimed to explore the anti- TNBC mechanisms of UA by network pharmacology and experimental validation. METHODS: TNBC cell lines MDA-MB-231 and BT-549 cells were treated with UA. A CCK-8 assay was performed to detect cell growth, while flow cytometry assessed cell cycle arrest and apoptosis. The underlying mechanism and potential targets of UA for TNBC treatment were investigated by network pharmacology, including PharmMapper database, GO, KEGG enrichment, and PPI analysis. The protein expressions and phosphorylation levels of FGFR1, AKT, and ERK were measured by western blot. Pull-down assay, cellular thermal shift assay (CETSA), and molecular docking were used to analyze the interaction between UA and FGFR1. Xenograft models were established to examine the effect of UA on TNBC tumor growth. RESULTS: UA effectively reduced cell viability, induced apoptosis, and arrested cell cycle in TNBC cells. Moreover, UA significantly regulated the expression of Bcl-2 and Bax to induce apoptosis. The results of network pharmacology and western blot suggested that UA reduced FGFR1/AKT/ERK pathway. Furthermore, pull-down, CETSA, and molecular docking results revealed that UA directly bound to FGFR1. In the xenograft model, UA inhibited the growth by suppressing FGFR1. DISCUSSION: In this study, we employed network pharmacology and experimental approaches to elucidate the mechanism of UA on TNBC. The results demonstrated that UA targeted FGFR1 to inhibit TNBC via mediating FGFR1/AKT/ERK pathway. CONCLUSIONS: Our findings demonstrate that UA inhibits the FGFR1/AKT/ERK pathway by directly targeting FGFR1, thereby suppressing TNBC progression and supporting its potential as a therapeutic agent for TNBC treatment.
Genetic and Molecular Determinants of Immunotherapy Response in Recurrent Ovarian Cancer.
Noori H, Khan SA, Alamin MH … +4 more , Zulfiqar K, Alibhai I, Sultany A, Mishra SK
Anticancer Agents Med Chem · 2025 Aug · PMID 40849752 · Publisher ↗
Ovarian cancer remains a significant public health challenge. It originates in the ovaries and presents in various histological subtypes. Surgery and chemotherapy are the most suitable treatments to combat this disease....
Ovarian cancer remains a significant public health challenge. It originates in the ovaries and presents in various histological subtypes. Surgery and chemotherapy are the most suitable treatments to combat this disease. This study aims to provide insights into the mechanisms and biological complexity needed to understand the pathogenesis of recurrent ovarian cancer. A thorough review of the relevant literature on recurrent ovarian cancer and immunotherapy was conducted to gather information on genetic factors, immune responses, therapeutic strategies, and other pertinent data. The findings were analyzed and discussed to provide an in-depth understanding aligned with the study's objectives. Recurrent ovarian cancer is a major clinical challenge that occurs when the disease returns after initial treatment and a period of remission. Recurrence typically arises when residual cancer cells remain in the body after treatment, eventually leading to disease progression. Genetic factors, including mutations in BRCA1/BRCA2 and other genetic markers, play a crucial role in ovarian cancer recurrence and influence responses to therapies. The immune system's response to cancer cells is also critical, with therapeutic interventions either enhancing or reducing efficacy. The complex mechanisms underlying ovarian cancer and its recurrence have left many aspects of the disease pathway still to be fully understood. In conclusion, a comprehensive understanding of genetic and immune factors is crucial for developing effective and personalized treatments.
Design, Synthesis, Antimicrobial and Antitumor Activities of Benzo[f]chromene Derivatives: DFT and Molecular Docking.
Borik RMA, Abdelwahab AHF, Alamri AA … +7 more , Mohamed HM, Mostafa MS, El-Aassar MR, Ismail KS, Al-Dies AM, Elhenawy AA, El-Agrody AM
Anticancer Agents Med Chem · 2025 Aug · PMID 40849744 · Publisher ↗
INTRODUCTION: Benzochromenes are heterocyclic compounds of growing interest in medicinal chemistry due to their diverse biological activities, including antioxidant, anticancer, and antimicrobial properties. METHODS: A o...
INTRODUCTION: Benzochromenes are heterocyclic compounds of growing interest in medicinal chemistry due to their diverse biological activities, including antioxidant, anticancer, and antimicrobial properties. METHODS: A one-pot, three-component synthesis was employed to prepare benzochromene derivatives (4a-f) using 2-naphthol or its derivatives, active methylene compounds, and 2-methoxybenzaldehyde in ethanol with piperidine as a catalyst. The compounds were evaluated for their anticancer activity against MCF-7, HepG-2, and HCT-116 cell lines, as well as for their antimicrobial activity through molecular docking studies targeting cancerrelated and microbial proteins. RESULTS: All synthesized compounds were obtained in moderate to good yields. Compounds 4c, 4e, and 4f demonstrated superior biological activity compared to standard drugs Doxorubicin and Augmentin. Docking studies revealed strong binding affinities to key targets, including the TGF-βI receptor and the choline-binding domain. DISCUSSION: The hydroxyl group at position 9 in compounds 4c and 4f likely contributed to enhanced antimicrobial activity, while the bromo group in 4e correlated with significant anticancer effects. These findings suggest meaningful structure-activity relationships and validate the design strategy. CONCLUSION: The synthesized benzochromene derivatives exhibit promising anticancer and antimicrobial activities. Supported by molecular docking, these findings lay the groundwork for further pharmacological and in vivo evaluations of this scaffold.
Gaussian-based 3D-QSAR and Pharmacophore Mapping Studies of Indole Derivatives as Aromatase Inhibitors.
Bhatia N, Thareja S
Anticancer Agents Med Chem · 2025 Aug · PMID 40820449 · Publisher ↗
INTRODUCTION: Aromatase inhibition is one of the most effective strategies for the treatment of ER+ breast cancer, which accounts for about 70% of breast cancer cases. Indole-based aromatase inhibitors have altered the d...
INTRODUCTION: Aromatase inhibition is one of the most effective strategies for the treatment of ER+ breast cancer, which accounts for about 70% of breast cancer cases. Indole-based aromatase inhibitors have altered the dynamics of the search for anti-breast cancer drugs with efficacy in nanomolar concentrations. In the present study, we have integrated pharmacophore mapping with Gaussian-based 3D-QSAR analysis to map the essential pharmacophoric features of indole-based aromatase inhibitors, aiming to optimize lead molecules. METHODS: Pharmacophore mapping and Gaussian-based 3D-QSAR were integrated to identify the steric and electrostatic features essential for aromatase inhibitory activity. RESULTS: A Gaussian-based 3D-QSAR model with an r² value of 0.7621 and stability of 0.817 was generated to determine the nature of substitutions essential for optimal biological activity. Pharmacophore mapping results indicated that H-bond Donor (D), a Hydrophobic (H) feature, and three aromatic rings are essential for potent inhibitory activity. DISCUSSION: In order to identify important structural characteristics of indole-based aromatase inhibitors, the current study successfully integrated pharmacophore mapping investigations with 3D-QSAR. The developed molecule S1 demonstrated activity comparable to letrozole, with a predicted pIC50 value of 9.332 nM. CONCLUSION: The designed compound S1 demonstrated a predicted IC50 value of 9.332 nM, comparable to the most active compound 15 and the standard reference Letrozole. The developed models may be utilized by medicinal chemists for the optimization of new indole-based aromatase inhibitors for the effective treatment of ER+ breast cancer.
Timosaponin A-III Induces ROS-mediated Apoptosis and Triggers Protective Autophagy the AMPK/mTOR Pathway in Prostate Cancer.
Wu J, Li J, Guo Q … +5 more , Xiao C, Zhang Y, Wang D, Wu Q, Qiu J
Anticancer Agents Med Chem · 2026 · PMID 40820448 · Publisher ↗
INTRODUCTION: Timosaponin A-III (TAIII) is an effective anti-tumor ingredient extracted from the rhizomes of . However, the effect of TAIII on prostate cancer cells (PCa) and its underlying mechanisms is rarely investiga...
INTRODUCTION: Timosaponin A-III (TAIII) is an effective anti-tumor ingredient extracted from the rhizomes of . However, the effect of TAIII on prostate cancer cells (PCa) and its underlying mechanisms is rarely investigated. The current study aimed to investigate the anti-tumor effect and potential mechanisms of TAIII in PCa cells. METHODS: The effect of TAIII on the cell proliferation of PCa was evaluated by CCK-8 assay, colony formation assay, and EDU assay. Cell apoptosis and reactive oxygen species (ROS) production were evaluated by flow cytometry. The puncta of LC3 were detected by immunofluorescence analysis. The protein levels of apoptosis, autophagy, and AMPK/mTOR pathway were assessed by western blot. Finally, a PC3 xenograft nude mouse model was constructed to determine the effect of TAIII combined with chloroquine (CQ) in vivo. RESULTS: Our data showed that TAIII inhibited the proliferation of PCa cells and induced ROS-dependent apoptosis. TAIII treatment dramatically promoted the formation of LC3-positive puncta, and increased the expression of LC3B-II and P62 protein. Moreover, the combination of TAIII with CQ significantly enhanced the pro-apoptosis effect of TAIII in PCa cells and the PC3 xenograft model. In addition, the activation of the AMPK/mTOR pathway and the induction of autophagy induced by TAIII were reversed by Compound C. Suppressing AMPK with Compound C enhanced the apoptosis induced by TAIII in PCa cells. DISCUSSION: This study establishes TAIII as a potent anti-prostate-cancer agent that kills tumor cells via ROSdriven apoptosis while simultaneously triggering cytoprotective autophagy through the AMPK-mTOR axis. However, TAIII's clinical potential awaits pharmacokinetic, bioavailability, and toxicity evaluation. CONCLUSION: TAIII induced ROS-mediated cell apoptosis and promoted cytoprotective autophagy via the AMPK/mTOR pathway in PCa. These findings may provide a new strategy for combining TAIII with CQ together for PCa treatment.
Molecular Pathways and Biomarkers in Endometrial Carcinoma: Paving the Way for Precision Medicine.
Sharma KK, Tamta S, Pandey M … +2 more , Gupta R, Kumar G
Anticancer Agents Med Chem · 2026 · PMID 40798981 · Publisher ↗
Endometrial carcinoma (EC) is one of the most prevalent gynecological malignancies, with an increasing incidence globally. This review explores the role of molecular markers in revolutionizing the diagnosis, prognosis, a...
Endometrial carcinoma (EC) is one of the most prevalent gynecological malignancies, with an increasing incidence globally. This review explores the role of molecular markers in revolutionizing the diagnosis, prognosis, and management of EC. This article provides an overview of endometrial carcinoma, emphasizing its subtypes and the molecular mechanisms driving disease progression. Current biomarkers, while clinically significant, often present limitations in sensitivity, specificity, and predictive value, necessitating the discovery of novel markers. Recent advances in genetic and epigenetic profiling have identified key mutations, such as PTEN, TP53, and POLE, along with DNA methylation patterns and microRNAs, as crucial contributors to EC pathophysiology. Furthermore, transcriptomic and proteomic studies reveal the potential of RNA-based markers (e.g., lncRNAs, mRNAs) and proteomic signatures in improving early diagnosis and prognostic predictions. Immunohistochemical markers and insights into tumor microenvironment dynamics pave the way for targeted therapeutic strategies. In the context of endometrial carcinoma (EC), clinical trials play a pivotal role in validating targeted therapies based on molecular subtypes and biomarkers, such as HER2 amplification, POLE mutations, and mismatch repair deficiency (MMRd). This review underscores the integration of biomarkers into precision oncology, enabling personalized treatment regimens. However, challenges such as barriers to clinical translation and the need for advanced technologies highlight the importance of continued research in marker discovery for EC.
The Hematological Variations and Effect of Cadmium Induced Toxicity on Mammary Tumors Development in Albino Mice. A Comparative Model Study on the Effect of Heavy Metals in Human Breast Cancer.
Munir S, Nawaz Y, Tanvir F … +1 more , Anjum KM
Anticancer Agents Med Chem · 2025 Aug · PMID 40798956 · Publisher ↗
INTRODUCTION: Breast cancer develops in breast tissues, in ducts and lobules. It affects both genders, though it is uncommon in men. Hematological variations are important considerations and deficiencies in metals can ne...
INTRODUCTION: Breast cancer develops in breast tissues, in ducts and lobules. It affects both genders, though it is uncommon in men. Hematological variations are important considerations and deficiencies in metals can negatively impact human health. Cadmium is highly toxic and plays role in breast cancer progression. This study was designed for hematological variations and cadmium induced toxicity in mice and humans causing breast cancer. METHODS: Mice, obtained from local supplier, housed at university laboratory for 11 weeks, exposed to cadmium. Following dissection, blood and organs were harvested for examination. Histological analysis of liver and mammary gland tissues was conducted. RESULTS: Affected mice had higher Hb, RBC, HCT, MCV, and MCH, while humans showed lower Hb, HCT, and MCV but similar RBC and MCH. Other blood values also show changes. Histopathology revealed changes in mammary glands (higher cadmium led to increased fat deposition, degeneration of alveolar epithelial cells, and a reduction in alveolar milk lumen size, indicating compromised glandular function) and Liver damage (vacuolation, lipid accumulation, fibrosis, and collagen deposition, was noticeable with prolonged cadmium). These changes causes liver fibrosis and impaired mammary gland function. DISCUSSION: The cadmium exposure induces distinct hematological alterations and severe tissues damage, reflecting species-specific responses. The observed liver fibrosis and mammary gland dysfunction emphasize cadmium's potential to compromise critical organ functions over time. CONCLUSION: Significant effects of cadmium exposure in mice were observed. Histological damage was seen in mammary glands and liver. Further research on protective measures and dose-response relationships for cadmium exposure is needed.
Serotonin Metabolism Shapes the Tumor Immune Microenvironment and Serves as a Therapeutic Target in Lung Cancer.
Yasen M, Sun N, Jia J … +5 more , Hong W, Zhuang L, Huang J, Chen X, Shen W
Anticancer Agents Med Chem · 2025 Aug · PMID 40798955 · Publisher ↗
INTRODUCTION: Lung cancer progression involves complex interactions between metabolic pathways and the immune microenvironment. The role of serotonin, a tryptophan-derived metabolite, in immune responses to lung tumors r...
INTRODUCTION: Lung cancer progression involves complex interactions between metabolic pathways and the immune microenvironment. The role of serotonin, a tryptophan-derived metabolite, in immune responses to lung tumors remains unclear. METHODS: An orthotopic lung cancer model was established by intravenously injecting KP (KrasG12D/p53-/-) cells into C57BL/6 mice. Metabolomic and flux analyses were conducted on tumor versus normal lung tissues. Serotonin was administered to tumor-bearing mice, followed by immunofluorescence and flow cytometry to assess immune responses. Human lung cancer datasets were analyzed to validate clinical relevance. RESULTS: Tumor tissues exhibited a significant decrease in serotonin levels. Although tryptophan, serotonin, and kynurenine levels were decreased overall, flux analysis revealed a metabolic shift favoring kynurenine synthesis, with a ~10-fold increase in the kynurenine-to-serotonin ratio. Serotonin supplementation significantly prolonged survival and enhanced dendritic cell and CD8⁺ T cell infiltration and activation in tumors. Analysis of public datasets showed that serotonin expression positively correlated with CD8⁺ T cell activation signatures and patient prognosis. DISCUSSION: By revealing serotonin as a potential biomarker and therapeutic target, this study paves new avenues for improving lung cancer treatment strategies through modulation of the immune microenvironment. Moreover, the precise receptor-mediated mechanisms underlying serotonin's immunomodulatory effects remain to be clarified, and translational validation in human tissues is warranted to strengthen clinical relevance. CONCLUSION: Serotonin deficiency in the tumor microenvironment of the lung suppresses antitumor immunity. Its restoration reverses immune dysfunction and limits tumor progression. These findings identify serotonin as a potential metabolic regulator and immunotherapeutic target in lung cancer.
Retraction Notice to "The Natural Flavonoid Naringenin Inhibits the Cell Growth of Wilms Tumor in Children by Suppressing TLR4/NF-κB Signaling".
Li H, Chen P, Chen L … +1 more , Wang X
Anticancer Agents Med Chem · 2025 · PMID 40792466 · Publisher ↗
The publisher has retracted the article "The Natural Flavonoid Naringenin Inhibits the Cell Growth of Wilms Tumor in Children by Suppressing TLR4/NF-κB Signaling," which was published in Anti-Cancer Agents in Medicinal C...
The publisher has retracted the article "The Natural Flavonoid Naringenin Inhibits the Cell Growth of Wilms Tumor in Children by Suppressing TLR4/NF-κB Signaling," which was published in Anti-Cancer Agents in Medicinal Chemistry (https://www.eurekaselect.com/article/109234) in Volume 21, Issue 9, 2021. This was done after a thorough investigation that may have revealed inaccurate scientific information that identified G401 and SKNEP1 as Wilms tumor cell lines, even though they are not Wilms tumor cell lines. As a result, the integrity and validity of the data presented could not be confirmed. The retraction has been made in agreement with the Editor-in-Chief. Despite multiple attempts, the authors did not respond to correspondence regarding this matter. The publisher regrets any inconvenience caused to the readers and the scientific community. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
Anticancer Efficacy and Metabolomic Profiling of Leaf Extracts: and Approaches.
Kaneria M, Rakholiya K, Patel D … +8 more , Patel M, Kalam MA, Syed R, Sambad VG, Padariya DB, Faldu A, Sahoo DK, Patel A
Anticancer Agents Med Chem · 2026 · PMID 40776651 · Publisher ↗
INTRODUCTION: Current research focuses on identifying and analyzing bioactive metabolites with significant therapeutic properties derived from L. (Pomegranate) leaves. METHODS: The biological potential of these metaboli...
INTRODUCTION: Current research focuses on identifying and analyzing bioactive metabolites with significant therapeutic properties derived from L. (Pomegranate) leaves. METHODS: The biological potential of these metabolites was evaluated through anticancer activity. In contrast, LC-QTOF-MS and GC-QTOF-MS methods were used to profile the metabolites. In silico molecular docking was performed using various online and offline tools to validate the active metabolites. RESULTS: PAC exhibited significant anticancer activity. The identified metabolites were screened, and 40 compounds from different categories were chosen for further interaction studies. DISCUSSION: The molecular docking analysis discovered lead molecules that exhibited promising binding energy scores, efficiency, and stable modulation with specific protein domains. However, clinical trials are required for the applications of the lead molecules in the design of anticancer drugs. CONCLUSION: The findings from both and analyses support the notion that the P. granatum Acetone Extract (PAC) is an excellent source of potential metabolites with therapeutic properties. According to the findings, this research enhances the treatment of human breast cancer and validates several plant traditions for their numerous benefits.
Bioinformatics And Experimental Insights Into Sotorasib Resistance Mechanisms in Non-small-cell Lung Cancer.
Li D, Lyu G
Anticancer Agents Med Chem · 2025 Aug · PMID 40776650 · Publisher ↗
INTRODUCTION: This study aims to identify the key genes and pathways associated with sotorasib resistance in Non-Small Cell Lung Cancer (NSCLC) using bioinformatics analyses and experimental validation, with a focus on u...
INTRODUCTION: This study aims to identify the key genes and pathways associated with sotorasib resistance in Non-Small Cell Lung Cancer (NSCLC) using bioinformatics analyses and experimental validation, with a focus on uncovering the potential mechanisms underlying resistance. METHODS: We compared gene expression profiles between sotorasib-resistant (SR) and non-resistant NSCLC cell lines using the GSE229070 dataset and between NSCLC tissues and adjacent normal tissues using the GSE18842 dataset. Differentially expressed genes (DEGs) were identified and intersected across datasets using the Venn diagram package. Functional enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The transcriptional activity and prognostic impact of key genes were evaluated using the UALCAN portal and Kaplan-Meier Plotter, respectively. The correlation between gene expression and immune cell infiltration was analyzed using the TIMER database, and co-expressed genes were explored using LinkedOmics. qRT-PCR and Western blot were used to validate the expression of AREG in parental and SR cell lines. RESULTS: We identified 33 overlapping DEGs, including TENM2, COL12A1, COL5A2, and LRRC15 (upregulated) and AREG (downregulated). AREG expression was significantly lower in NSCLC patients and associated with worse survival outcomes. AREG expression was also correlated with the levels of immune cell infiltration. Functional enrichment analysis revealed that AREG was associated with pathways including the NOD-like receptor signaling pathway, focal adhesion, DNA replication, and homologous recombination. Experimental validation confirmed that AREG mRNA and protein levels were significantly reduced in HCC78-SR cells compared to parental HCC78 cells. DISCUSSION: The downregulation of AREG is closely associated with sotorasib resistance in NSCLC, potentially contributing to resistance through alterations in signaling pathways and the tumor immune microenvironment. This finding aligns with previous studies on AREG's role in drug resistance, highlighting its potential as a therapeutic target. However, limitations include reliance on publicly available datasets and the need for further validation in clinical cohorts. CONCLUSION: The study identifies AREG as a key gene associated with sotorasib resistance in NSCLC, suggesting its potential as a biomarker and therapeutic target. Further research is needed to elucidate the mechanisms underlying AREG's role in resistance and to explore its clinical significance.
dHG-5 Exhibits Dual Efficacy of Anti-Metastatic and Anti-hypercoagulability in Mice by Inhibiting Heparanase and Intrinsic Coagulation Pathway.
Tong Z, Xu Z, Yang W … +3 more , Song H, Zheng S, Zhou L
Anticancer Agents Med Chem · 2026 · PMID 40776649 · Publisher ↗
INTRODUCTION: Cancer metastasis and associated thrombosis are significant contributors to cancerrelated mortality, necessitating therapeutic strategies that simultaneously address both issues. This study aimed to evaluat...
INTRODUCTION: Cancer metastasis and associated thrombosis are significant contributors to cancerrelated mortality, necessitating therapeutic strategies that simultaneously address both issues. This study aimed to evaluate the dual anti-metastatic and anti-hypercoagulability properties of dHG-5, a low-molecular-weight fucosylated glycosaminoglycan derived from the sea cucumber . METHODS: The heparanase-inhibitory and anticoagulant effects of dHG-5 were assessed in vitro using biochemical assays. The impact of dHG-5 on 4T1 cell migration and invasion was evaluated using Transwell assays. The antimetastatic and anti-hypercoagulability efficacy of dHG-5 was further tested in a 4T1 mammary carcinoma mouse model, with enoxaparin (LMWH) used as a control. RESULTS: dHG-5 exhibited potent heparanase inhibition (IC = 91.0 nM) and significantly reduced 4T1 cell migration and invasion at 4.0 μmol/L. , dHG-5 reduced lung metastasis without affecting tumor growth or proliferation. At a dose of 20 mg/kg, dHG-5 prolonged activated partial thromboplastin time (APTT) from 23.5 ± 1.85 s to 30.4 ± 3.36 s, effectively reversing hypercoagulability in tumor-bearing mice. Compared to lowmolecular- weight heparin, dHG-5 selectively prolonged APTT with negligible effects on prothrombin time and thrombin time. DISCUSSION: The findings highlighted the dual-action mechanism of dHG-5, namely inhibiting heparanase and selectively targeting the intrinsic coagulation pathway. This selective action minimized bleeding risk, a common issue with traditional anticoagulants. However, this study focused on a single cancer type and the use of a mouse model, which may not fully represent human pathophysiology. We would explore dHG-5's effects across different cancer types and investigate its potential synergistic effects with existing cancer therapies in the future. CONCLUSION: dHG-5 suppressed metastasis and hypercoagulability through heparanase inhibition and selective action on the intrinsic coagulation pathway. These findings highlight dHG-5 as a promising dual-action therapeutic candidate for managing metastasis and cancer-associated thrombosis, offering a safer alternative to traditional anticoagulants.
A Comprehensive Overview of the Therapeutic Potential of Pyrimidine Analogues in the Management of Colorectal Cancer.
Sathishkumar M, Dhunmati K, Ramalakshmi N … +3 more , Nalini CN, Dibenthiran S, Indrakumar S
Anticancer Agents Med Chem · 2026 · PMID 40735982 · Publisher ↗
Colorectal cancer is the fourth most prevalent cause of cancer-related fatalities, and cancer is still one of the major causes of death globally. Although pyrimidine analogues can target abnormal cellular growth, they ha...
Colorectal cancer is the fourth most prevalent cause of cancer-related fatalities, and cancer is still one of the major causes of death globally. Although pyrimidine analogues can target abnormal cellular growth, they have demonstrated potential as therapeutic treatments for a variety of malignancies, including colon cancer. A vital nitrogen-containing aromatic heterocyclic molecule, pyrimidine is an important target for cancer treatments since it is involved in the construction of DNA and RNA. Recent research has investigated the synthesis and assessment of a number of pyrimidine derivatives, demonstrating their capacity to block particular enzymes and pathways linked to the development of cancer. According to the review, a number of pyrimidine-based chemical families, such as 1H-pyrazolo, diarylpyrazolo, and bromo-pyrimidine derivatives, have shown strong anti-cancer properties in preclinical models, especially against lung and colon cancer cell lines. Moreover, these compounds' structure-activity relationship (SAR) studies show that changes made at important positions on the pyrimidine scaffold improve their anticancer efficacy. These findings highlight the significance of further study into pyrimidine analogues as promising candidates for cancer therapy.
The Potential of Next-generation Multi-functional Nanoplatforms for Breast Cancer.
Gupta S, Urs TJ, Aggarwal N … +2 more , Sen S, Bondhopadhyay B
Anticancer Agents Med Chem · 2026 · PMID 40734427 · Publisher ↗
The next-generation nanoparticles overcome the drawbacks of early nanoplatforms by integrating multiple functions, such as drug delivery, controlled drug release, and combination therapy, into a single system. This study...
The next-generation nanoparticles overcome the drawbacks of early nanoplatforms by integrating multiple functions, such as drug delivery, controlled drug release, and combination therapy, into a single system. This study examines the biomedical applications of quantum dots, carbon nanotubes, superparamagnetic iron oxide nanoparticles, and layered double hydroxides for the delivery of breast cancer drugs. They are termed as "nextgeneration" nanoparticles, as they are advanced nanocarriers that offer a comprehensive and alternative approach towards breast cancer treatment, providing enhanced specificity and efficacy compared to their predecessors. The development of these nanoplatforms has significantly enhanced drug bioavailability and reduced toxicity. A comprehensive analysis of a nanotechnology-based drug delivery system was conducted. The keywords used for this review were "Breast Cancer", "Targeted Drug Delivery", "Quantum Dots", "Carbon Nanotubes", "Layer Double Hydroxides", and "Superparamagnetic Iron Oxide Nanoparticles". The inclusion criteria consisted of studies focusing on breast cancer, targeted drug delivery, and therapeutic applications of these nanocarriers. In contrast, exclusion criteria included studies focusing on the synthesis of nanocarriers and the diagnostic applications of these nanostructures. The study underscores their mechanisms, limitations, and future development directions. Additionally, the study tracks the evolution of the nanocarriers since their early discovery. Next-generation nanocarriers (QDs, CNTs, SPIONs, and LDHs) have strong therapeutic potential owing to their precisely engineered properties, such as size, shape, morphology, and surface modifications. Their trigger-initiated drug release mechanisms enable targeted delivery with a better rate of tumor penetration, while their ability to co-deliver multiple therapeutic agents addresses drug resistance issues and provides synergistic effects. Comparative analyses have revealed that these advanced nanoplatforms significantly outperform early-generation carriers in terms of bioavailability, reduced toxicity, and treatment efficacy across various breast cancer types. Next-generation nanoplatforms offer unprecedented opportunities for targeted and efficient cancer treatment. Continued research and innovation are necessary to address existing challenges and to optimize their therapeutic potential for clinical applications.
The Role of Kinase Inhibitors in Cancer Neuroscience: Mechanisms, Therapeutic Potential, and Future Directions.
Vlasiou MC
Anticancer Agents Med Chem · 2026 · PMID 40696545 · Publisher ↗
INTRODUCTION: Cancer progression is increasingly understood to be influenced by neural mechanisms, including neurotransmitter signaling, neurotrophic factor activity, neuroinflammation, and neurogenic inflammation. These...
INTRODUCTION: Cancer progression is increasingly understood to be influenced by neural mechanisms, including neurotransmitter signaling, neurotrophic factor activity, neuroinflammation, and neurogenic inflammation. These neurobiological interactions contribute to tumor proliferation, angiogenesis, and metastasis. Kinase inhibitors, a class of targeted therapies that block dysregulated kinase activity, have demonstrated promise not only in direct tumor suppression but also in modulating neural pathways associated with cancer progression. METHODS: This review examines the role of kinase inhibitors in modulating cancer-associated neural mechanisms. A comprehensive literature search was conducted to identify studies exploring the effects of kinase inhibition on: (1) neurotransmitter signaling pathways; (2) neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF); (3) neuroinflammation through glial cell modulation; and (4) neurogenic inflammation. Additionally, we assessed the impact of kinase inhibitors on tumor-induced axonogenesis and stress-related signaling. Clinical relevance was evaluated through analysis of preclinical models, human case studies, and outcomes from relevant clinical trials. RESULTS: Kinase inhibitors were found to significantly modulate neural factors that facilitate tumor growth. Specifically, they can suppress neurotrophic signaling (e.g., NGF/TrkA, BDNF/TrkB), inhibit glial activation, reduce pro-inflammatory cytokine production, and block neurotransmitter-induced proliferation. Inhibition of stress-responsive kinases such as p38 MAPK and JNK also disrupted tumor-associated axonogenesis and inflammation. Clinical trials demonstrate improved outcomes in cancers such as glioblastoma, breast cancer, and pancreatic cancer when kinase inhibitors are employed with consideration of neural mechanisms. DISCUSSION: These findings support the emerging concept of targeting the neural tumor microenvironment as a therapeutic strategy. Kinase inhibitors represent a dual-action approach, suppressing both cancer cell intrinsic growth pathways and the neural factors that sustain them. However, several challenges persist, including resistance mechanisms, variability in patient neural profiles, and off-target effects. Future research should focus on the development of neural-specific kinase inhibitors, the use of neural biomarkers for therapy selection, and the integration of neuro-oncology into personalized treatment plans. CONCLUSION: Kinase inhibitors offer a promising frontier in cancer treatment by targeting neural mechanisms that contribute to tumor progression. While current evidence is encouraging, further investigation is required to optimize their use within neuro-oncology. Personalized approaches and novel targets within the neural-cancer axis will be essential for translating this strategy into clinical practice and improving long-term patient outcomes.
Polyamines in Cancer: Mechanisms, Metabolic Targets, and Therapeutic Opportunities.
Yerlikaya A
Anticancer Agents Med Chem · 2026 · PMID 40685729 · Publisher ↗
INTRODUCTION: Polyamine metabolism is essential for cancer cell growth, with enzymes like ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) playing key roles in polyamine (PA) biosynthesis....
INTRODUCTION: Polyamine metabolism is essential for cancer cell growth, with enzymes like ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) playing key roles in polyamine (PA) biosynthesis. These polyamines (putrescine, spermidine, and spermine) regulate vital cellular processes, including DNA replication, protein synthesis, and cell cycle progression. Dysregulated polyamine metabolism is common in cancer, making ODC and AdoMetDC attractive therapeutic targets. This review highlights polyamines' role in cancer and explores combination therapies targeting polyamine metabolism and critical signaling pathways for improved clinical outcomes. METHODS: A comprehensive analysis of both historical and recent literature on polyamine metabolism in cancer was performed using PubMed, which provides access to over 37 million citations from biomedical literature. Expression data for key polyamine biosynthetic enzymes, ODC and AdoMetDC, were obtained from the UALCAN portal - an interactive web resource for the analysis of cancer OMICS data. The IUPAC names of drugs and inhibitors targeting the polyamine pathway were retrieved from the PubChem database and used to generate molecular structures using the BIOVIA Draw 2025 program. Additionally, the ClinicalTrials.gov database was explored to identify ongoing and completed clinical research studies, as well as to gather detailed information on therapeutic agents targeting polyamine metabolism. RESULTS: Aberrant polyamine metabolism in cancer is driven by oncogenic pathways like MYC, Akt, and mTOR. MYC upregulates ODC1, promoting polyamine dysregulation. Defects in enzymes such as MTA phosphorylase (MTAP) enhance cancer cell sensitivity to inhibitors of purine/pyrimidine synthesis and the ubiquitin-proteasome pathway, suggesting alternative therapeutic strategies. DISCUSSION: Therapeutic strategies combining polyamine biosynthesis inhibition with targeting nucleotide synthesis or proteasome function have shown synergistic potential. However, the dual nature of polyamines - supporting both, tumor growth and ferroptotic cell death - poses a therapeutic challenge. Balancing these effects is key to designing effective interventions. Advancing this field requires not only selective inhibitors but also a deeper understanding of context-dependent polyamine functions in tumor biology. CONCLUSION: Developing more potent inhibitors with improved drug-like properties is crucial for advancing polyamine- targeted therapies and positioning this field at the forefront of cancer research.
Innovative Nanocarriers: Magnetosomes in the Fight against Cancer.
Yadav S, Mishra MK
Anticancer Agents Med Chem · 2026 · PMID 40685728 · Publisher ↗
Recent advancements in medication formulations and drug delivery systems over the past two decades have improved patient adherence and pharmacological responses. Efficient, target-specific medication delivery remains cha...
Recent advancements in medication formulations and drug delivery systems over the past two decades have improved patient adherence and pharmacological responses. Efficient, target-specific medication delivery remains challenging, with many current systems designed to minimize drug loss and degradation. Magnetosomes, as nanocarriers, show promise for delivering antibodies, vaccine DNA, and siRNA, enhancing the stability of chemotherapeutics, and enabling targeted delivery to malignant tumors. Targeted drug delivery is crucial in cancer treatment, as anticancer drugs often cannot differentiate between healthy and malignant cells, causing side effects and systemic toxicity. Magnetosome-based drug delivery offers a potential solution, minimizing adverse effects and promoting drug accumulation at the target site. This review covers the design, development, and advancements in magnetosome-based drug delivery for cancer therapy.
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