Search Results (889)

Background: Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) primarily participates in protein synthesis by binding aminoacyl-tRNA complexes to facilitate peptide chain elongation on ribosomes. Its expression and functional roles exhibit significant heterogeneity across various malignancies, exerting dual regulatory effects as both an oncogene and a tumor suppressor. This study aims to investigate the potential prognostic value and tumor-suppressive role of EEF1A1 in kidney renal clear cell carcinoma (KIRC). Methods: We analyzed the differential expression of EEF1A1 in KIRC and its correlation with patient prognosis based on the TCGA, GEO, and HPA databases. The STRING and GEPIA databases were utilized to perform functional enrichment analysis of its interacting proteins and co-expressed genes. The xCell algorithm was employed to assess the correlation between EEF1A1 and immune cell infiltration, immune checkpoints, and immunomodulatory molecules. Furthermore, drug sensitivity analysis was conducted to evaluate its clinical application potential. Finally, the expression of EEF1A1 in 786-0 and A498 cell lines was validated via qRT-PCR and Western blotting. Furthermore, CCK-8, wound healing, and Transwell migration/invasion assays were performed to evaluate cell proliferation, migration, and invasion, respectively. Results: EEF1A1 may function as a negative regulator of malignant behaviors in KIRC tissues and cell lines, and its expression level was closely associated with clinicopathological features and prognosis of patients. GO, KEGG, and GSEA enrichment analyses revealed that low EEF1A1 expression is closely linked to immunosuppressive pathways. Further immunological analysis confirmed significant correlations between EEF1A1 and various immune cell infiltrates, immune checkpoints, tumor-infiltrating lymphocytes, and immunomodulatory molecules. Moreover, cells with high EEF1A1 expression exhibited increased sensitivity to anti-tumor drugs, with expression levels negatively correlated with inhibitory activity (IC50). Finally, overexpression of EEF1A1 significantly inhibited the proliferation, migration, and invasion of clear cell renal cell carcinoma cells. Conclusions: EEF1A1 serves as a potential prognostic biomarker in KIRC and is associated with clinical progression, immune-related characteristics, metabolic pathways, and drug sensitivity. Functional validation further supports its role in regulating malignant phenotypes of KIRC cells. Full article

Although advances in pediatric oncology have resulted in cure rates exceeding 80% among children with cancer, progress in survival outcomes has begun to plateau in recent years. Mortality in this population remains largely associated with aggressive disease features, particularly tumor resistance to chemotherapy and metastatic spread. At the same time, the growing population of childhood cancer survivors has drawn increasing attention to the persistent and potentially serious late effects associated with conventional chemotherapy. Thus, it is crucial to discover drugs with specific antitumor action, effective and safe drugs that, combined with chemotherapy or radiotherapy, could chemosensitize or radiosensitize the tumor and reduce the severe side effects of both. Substance P (SP) peptide and its Neurokinin-1 receptor (NK-1R) are known to be involved in pediatric cancer, promotion and progression. Pediatric cancer overexpresses SP/NK-1R and NK-1R is essential for viability of cancer cells and is not essential for normal non-tumor cells. SP induces mitogenesis, exerts anti-apoptotic effects, and promotes angiogenesis, invasion and migration for metastasis in cancer cells and produces inflammation. Conversely, NK-1R antagonists, such as aprepitant and similar drugs, inhibit mitogenesis and induce apoptosis in pediatric cancer cells in a concentration-dependent manner. They also inhibit angiogenesis, invasion, and migration in pediatric cancer cells and have an anti-inflammatory effect. Moreover, aprepitant in combination with chemotherapy or radiotherapy can produce chemosensitization or radiosensitisation and decreases the severe side effects of both. This review updates the role of the SP/NK-1R axis in pediatric cancers and analyzes its potential as a therapeutic target. It highlights NK-1R antagonists, particularly aprepitant, and their potential as drugs for the treatment of pediatric cancer. Full article

Background: Glioblastoma (GBM) is a primary malignant tumor of the central nervous system and has a high lethal rate despite therapeutic advances. Although immunotherapies have achieved great success in solid tumors, the highly immunosuppressive tumor microenvironment and the blood–brain barrier (BBB) obstruction hinder the development of immunotherapies for GBM. In this study, we innovatively developed a nanohydrogel composite vaccine (nanoCOM-GEL) for GBM immunotherapy via intranasal immunization. Methods: The nanoCOM-GEL used GelMA as the hydrogel matrix and was co-formulated with antigenic peptides, the BBB-penetrating peptide (peptide 22), as well as immune cell stimulants and chemokines. The efficiency of this vaccine in bypassing the BBB and its capacity to induce anti-GBM immune responses were evaluated in vitro and in vivo. Results: The nanoCOM-GEL vaccine demonstrated superior BBB-bypassing and BBTB-penetrating capabilities, potent immunostimulatory activity, and effective GBM-targeting efficacy, as validated in both cellular and animal models. In an orthotopic GBM mouse model (n = 8 per group), intranasal immunization with nanoCOM-GEL significantly extended median survival from 21 days (control group) to more than 60 days (nanoCOM-GEL group), representing a 2.8-fold increase (p < 0.001). The vaccine markedly inhibited tumor growth, as evidenced by an 82.5% reduction in tumor tissue at day 21 compared to controls (p < 0.01). Mechanistically, nanoCOM-GEL increased intratumoral CD8⁺ T cell infiltration by 9.5-fold and upregulated DCs by 6.4-fold, while simultaneously reducing intratumoral M2-type tumor-associated macrophages by 79.3% (p < 0.001), effectively reshaping the immunosuppressive tumor microenvironment. Conclusions: This innovative nanoCOM-GEL vaccine achieved potent anti-GBM therapeutic efficacy and provided a promising strategy for effective GBM immunotherapies. Full article

Tumor angiogenesis plays a critical role in cancer growth and metastatic progression and therefore represents an important therapeutic target. Bee venom-derived peptides constitute a diverse source of bioactive molecules whose interactions with angiogenesis-associated receptors remain incompletely characterized. In this study, an integrated in silico workflow was applied to investigate the potential interactions of selected bee venom peptides, including melittin and tertiapin, with major angiogenic-associated receptors, including platelet-derived growth factor receptor alpha (PDGFR-α), vascular endothelial growth factor receptors, fibroblast growth factor receptors, and integrin αvβ3. Molecular docking was used to identify and prioritize potential peptide–receptor complexes, while molecular dynamics simulations were performed to assess their conformational stability and interaction patterns under the simulated conditions. Reactome pathway enrichment analysis was subsequently used to contextualize the selected molecular targets within angiogenesis-related biological processes. Melittin–PDGFR-α and tertiapin–integrin αvβ3 emerged as the highest-ranked complexes and exhibited relatively stable interaction patterns with persistent intermolecular contacts throughout the simulations. Pathway enrichment analysis further associated the investigated targets with PDGFR signaling, cell migration, and other angiogenesis-related processes. Collectively, these findings suggest that melittin–PDGFR-α and tertiapin–integrin αvβ3 represent promising peptide–receptor pairs for further investigation while providing a computational rational for exploring bee venom peptides as potential modulators of tumor angiogenesis. However, these findings should be considered hypothesis-generating and primarily serve to prioritize peptide-receptor pairs for future experimental validation, including binding assays, cellular assays, and relevant in vivo studies. Peptide selectivity, toxicity, stability, and targeted delivery should also be evaluated before any therapeutic application can be considered. Full article

Globally, cancer has emerged as a major cause of human death, and the traditional therapy suffers several drawbacks such as poor survival rate, potential side-effects and increased drug resistance. Recently, natural bioactives obtained by valorization of food and agricultural wastes have drawn great attention as a promising alternative cancer therapeutic. This study aims to evaluate the antitumor efficiency of low-molecular-weight collagen peptides (TSP) isolated from Taiwan tilapia skin, as well as their nanoemulsion (TSPE) and nanoliposome (TSPL) without or with folic acid-chitosan (FC) ligand conjugation (TSPE-FC and TSPL-FC) in comparison with paclitaxel using a nude mice model. Based on the optimized enzymatic hydrolysis conditions, TSP was prepared using alcalase 12.5%, sample-to-water ratio 1:30 (w/v), pH 8, temperature 50 °C and hydrolysis time 6 h. TSP containing a high proportion of 172 Da fragment (48%) and hydrophobic amino acids (67.2%) was subsequently incorporated into two nanoformulations, with TSPE being prepared with an optimal ratio of soybean oil, lecithin, glycerol, Tween 80 and deionized water, while TSPL was prepared with ethanol, cholesterol, phosphatidylcholine, Tween 80, glycerol and deionized water. The mean particle sizes of TSPE and TSPL were, respectively, 16.1 nm and 33.9 nm, which changed to 15.2 nm and 35.3 nm upon FC conjugation, along with a shift in zeta potential from negative (−41.7 mV for TSPE and −46.6 mV for TSPL) to positive (+23.2 mV for TSPE and +23.9 mV for TSPL), which is favorable for tumor cell penetration and uptake. Nanopeptides showed a sustained release of TSP in an in vitro release study compared to a rapid release from nonencapsulated TSP. Following treatment of A549 cell-induced nude mice tumors with TSP, TSPE, TSPL, TSPE-FC and TSPL-FC at two different doses (100 and 300 mg/kg body weight (BW)) as well as paclitaxel (15 mg/kg BW), the tumor volume, respectively, decreased by 22.4–43.3%, 40.4–70.6%, 36.9–69.2%, 59.1–78.6%, 71.5–85.7% and 90.9%, while the tumor weight reduced by 18.2–48.0%, 42.6–73.0%, 36.1–69.6%, 58.8–79.5%, 69.6–85.2% and 90.3%. In addition, a decrease in the levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) were shown in mice serum for all treatments, with paclitaxel being the most effective in inhibiting tumor growth, followed by TSPL-FC/TSPE-FC, TSPE/TSPL and TSP. Collectively, both nanoencapsulated peptides and FC conjugated nanopeptides showed the most pronounced effect in inhibiting lung cancer tumors in mice. Full article

Persistently poor glioblastoma (GBM) survival necessitates better elucidation of tumor drug responses. After observing that low curcumin and all-trans retinoic acid (ATRA) doses stimulated cell proliferation and counteracted each other’s high-dose antiproliferative effects in U87 GBM cells, drug influences on cell growth, migration, and death and the antiproliferative interaction proteome were further studied. Cell proliferation and migration were assessed by xCELLigence Real-Time Cell Analysis (RTCA). Cell death was defined using flow cytometry. Drug interactions were determined with CompuSyn software (version 1.0). Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS), High-Performance Liquid Chromatography (HPLC), and SequestHT software (version 1.4) were utilized for peptide generation and identification. ATRA at high doses inhibited cell growth and migration more efficiently. Curcumin was more proliferative and antagonistic against anti-growth effects at low doses. Migration inhibition and apoptosis occurred synergistically at the highest drug doses. ATRA influenced the proteome more remarkably, reducing Transforming Growth Factor Beta Induced (TGFBI), Phosphoglycerate Dehydrogenase (PHGDH), tenascin, and Sequestosome 1 (SQSTM1). These effects were alleviated by curcumin, except for SQSTM1. Uveal Autoantigen With Coiled-Coil Domains And Ankyrin Repeats (UACA) and Sad1 And UNC84 Domain Containing 2 (SUN2) were increased by ATRA and curcumin, and to a lesser extent by the combination. Hexokinase 2 (HXK2) was increased by curcumin and the combination. Heme Oxygenase 1 (HMOX1) was depleted by the combination, but not by the single agents. SQSTM1 and HMOX1 reductions may mediate anticancer synergism, while the remaining changes may indicate ongoing hormetic pathways not reflected in cell counts. Full article

Soluble variants of recombinant T cell receptors (TCRs) have become attractive tools for the retargeting of cytotoxic T cells toward intracellular tumor or viral antigens by combining them with CD3-binding antibodies in bispecific T cell engagers; however, TCR-based NK cell engagers have not been studied so far. Here, we developed TCR-based bispecific agents for the redirection of NK cells utilizing a bivalent IgG1-like format. Trifunctional NK engagers included an Fc part with enhanced binding to FcγRIII/CD16A and single-chain (scFv) antibodies recognizing either NKp46 or CD16A, activating NK cell receptors. HCMV pp65/HLA-A2 reactive TCR-scFv-Fc fusion proteins incorporating an affinity-matured TCR and anti-NKp46 scFv activated peripheral blood NK cells and induced cytotoxicity in an antigen-specific manner. For T cell redirection, TCR-scFv-Fc fusion proteins included an scFv antibody recognizing CD3ε. Compared with NK cell engagers, T cell engagers showed similar sensitivity but lower peptide selectivity. For two TCRs recognizing melanoma-associated peptides, affinity-matured TCR-scFv-Fc fusion proteins enabled NK and T cell redirection and activation, and killing of tumor target cells loaded with exogenous peptides. Our results expand the versatility of the soluble TCR technology to NK cell engagers; however, they still require improvement in sensitivity to target tumor cells with low peptide/MHC-I complex densities. Full article

Background and Objective: Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense extracellular matrix (ECM) with overexpression of extra domain B fibronectin (EDB-FN). Methods: Herein, we investigated novel albumin-binding peptide–drug conjugates, Mc-ZD2-SN38 and SSC-ZD2-SN38, which integrate the prolonged circulation properties of albumin with the active targeting capability of the ZD2 peptide toward EDB-FN. Covalent and noncovalent albumin-binding strategies extended the half-life by approximately 100-fold and 15-fold, respectively, compared with the non-albumin-binding peptide–drug conjugate (PDC) (ZD2-SN38). Results: Notably, ZD2-mediated targeting markedly reduced payload accumulation in major organs, resulting in an improved safety profile. In a BxPC-3 xenograft model, Mc-ZD2-SN38 and SSC-ZD2-SN38 demonstrated potent and sustained antitumor efficacy. Conclusions: These findings establish a long circulation and active targeting drug delivery strategy, providing an ideal framework for the development of PDCs with enhanced therapeutic indices. Full article

Backgroundand Objectives: Endometrial cancer ranks among the most prevalent gynecologic malignancies in high-income countries, with increasing incidence and mortality driven by the global obesity epidemic. Evidence suggests that women with early-stage disease face a greater risk of death from obesity-related comorbidities than from cancer recurrence and that weight reduction is associated with improvements in quality of life and in the long-term burden of obesity-related morbidity and mortality. Minimally invasive (MIS) metabolic/bariatric surgery is the most effective treatment for achieving significant, sustained weight loss and comorbidities resolution/improvement. Advances in MIS (laparoscopic, robotic, and endoscopic) techniques have reduced perioperative morbidity and mortality. Novel pharmacotherapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), have recently received regulatory approval for weight management and ongoing studies are investigating their therapeutic impact on endometrial carcinogenesis and tumor biology. This review synthesizes and critically appraises evidence on metabolic interventions, including innovative bariatric techniques and pharmacologic agents, with the aim of informing their integration into multidisciplinary, risk-adapted management strategies for patients with severe obesity and endometrial cancer. Materials and Methods: A comprehensive review was conducted in accordance with SANRA (Scale for the Assessment of Narrative Review Articles) criteria. Results: Emerging evidence indicates that MIS metabolic/bariatric surgery combined with hysterectomy is feasible and may be integrated into the multidisciplinary management of selected patients with severe obesity and endometrial hyperplasia or carcinoma. GLP-1RAs may modulate both the obesogenic systemic milieu and selected tumor-associated pathways, although definitive clinical evidence of direct antitumor effect and oncologic benefit in endometrial cancer has not been established. Conclusions: Obesity is a modifiable risk factor for endometrial cancer. Metabolic/bariatric interventions represent a promising component of the comprehensive, patient-centered management of this disease. Prospective studies are essential to clarify the association between these interventions and longitudinal oncologic outcomes, the feasibility and potential benefits of combined approaches, and their differential impact according to the molecular classification of endometrial cancers. Although weight reduction is associated with a lower risk of endometrial cancer, a direct improvement in cancer-specific survival has not yet been demonstrated; weight-loss management therefore represents a promising component of care in the severely obese population, and its incorporation into formal guidelines requires confirmation in prospective studies. Full article

Growth factors are molecules that interact with specific membrane receptors and induce cellular proliferation. In malignancy, this growth factor–receptor interaction constitutes one of the “hallmarks of cancer” and may result in uncontrolled cell growth. Proadrenomedullin N-terminal 20 peptide (PAMP) derives from proadrenomedullin and acts as an angiogenic peptide, and recent studies suggest it may be a tumor growth factor. In addition, it has been suggested that CXCR7 may be PAMP’s membrane receptor in particular cell types. Here, we combined advanced docking and molecular dynamic simulation studies to evaluate PAMP’s binding to CXCR7. Then, we used two melanoma cell lines and checked whether PAMP influences their shape, proliferation, migration, and invasion capacities. The signal transduction activated by PAMP was tested by Western blotting, and receptor involvement was investigated with specific inhibitors. This study shows that PAMP binds to active site 1 of CXCR7. It also increases melanoma cell proliferation through an autocrine growth loop. In contrast, PAMP reduced migration and invasion of these cells in a dose-dependent manner. PAMP was also responsible for modifying the actin cytoskeleton of both cell lines, producing a more elongated morphology. In addition, the presence of PAMP elevated ERK and AKT phosphorylation and increased CXCR7 and β-arrestin expression. Furthermore, specific inhibitors confirmed that these effects are mediated by the CXCR7/CXCR4/β-arrestin axis. In summary, we have shown that PAMP acts as a growth factor for melanoma cells while reducing their migration and invasion potential. These effects seem to be mediated by the CXCR7/CXCR4/β-arrestin axis. Altogether, these results suggest that PAMP inhibitors may be used as antitumor agents in melanoma. Full article

Background: Soft-shelled turtle (Pelodiscus sinensis), traditionally used for both medicinal and culinary purposes, is rich in high-quality protein and amino acids, making it an excellent raw material for the preparation of bioactive peptides. In recent years, soft-shelled turtle peptides have gradually become a research focus due to their significant physiological functions, including antioxidant, immunomodulatory, and anti-fatigue activities. Methods: This review systematically sorts out and analyzes 76 relevant research papers published from 2002 to 2026 and comprehensively elaborates on the current state of soft-shelled turtle peptide research, encompassing sources, preparation, and purification strategies, while placing special emphasis on the diverse functional activities and the molecular mechanisms underlying the observed bioactivities. Results: For preparation, enzymatic hydrolysis has become the mainstream method due to its high efficiency and mild conditions; fermentation offers the advantages of low cost and the ability to simultaneously remove odours and enhance flavour, demonstrating good application potential. This review summarizes five key bioactivities, including antioxidant, anti-fatigue, antihypertensive, antitumor, and immunomodulatory effects, and specifically focusing on the current evidence from in vitro and animal studies. Antioxidant and antihypertensive activities have been validated in vivo, whereas the rest remain only tested in vitro, highlighting the need for deeper mechanistic investigation. Conclusions: The review provides an in-depth analysis of the molecular mechanisms through which soft-shelled turtle peptides exert their physiological activities, including free radical scavenging and the regulation of signaling pathways. This review highlights the potential of soft-shelled turtles as a sustainable source of bioactive peptides and offers strategic recommendations for future research. Full article

Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare malignant tumor arising from the olfactory epithelium of the sinonasal tract. Surgery combined with radiotherapy remains the standard treatment for localized disease, whereas chemotherapy is mainly used in advanced or recurrent cases. However, recurrent and metastatic ONB continues to present major therapeutic challenges, and traditional staging and histological grading systems cannot fully explain the marked differences in clinical behavior among patients. The primary objective of this review is to summarize recent advances in the molecular pathology, tumor microenvironment (TME), and emerging targeted therapeutic strategies in ONB. Emerging genomic and transcriptomic studies suggest that ONB comprises biologically heterogeneous tumors with distinct molecular and transcriptional programs associated with proliferation, neuroendocrine differentiation, angiogenesis, and stromal remodeling. Furthermore, we explore the increasing attention directed toward the TME, including immune-cell infiltration, angiogenic signaling, and immune checkpoint expression, which may influence therapeutic response. These molecular findings have generated interest in several potential targeted treatment strategies, including peptide receptor radionuclide therapy (PRRT), anti-angiogenic therapy, epigenetic-targeted therapy, immunotherapy, and DNA-damage-response-targeted approaches. Ultimately, although the current evidence remains limited because of the rarity of the disease, novel therapeutic strategies for ONB are emerging. In addition to summarizing the current landscape, this review discusses the translational challenges and future directions for precision oncology and biomarker-driven therapy, aiming to provide insights for improving individualized patient management. Full article

Background: Colorectal cancer (CRC) is a major clinical challenge due to high metastasis and therapy resistance. Photodynamic therapy (PDT) offers precise tumor ablation but lacks sustained anti-metastatic activity. Peptidic urokinase-type plasminogen activator (uPA) inhibitors suppress metastasis but suffer from short half-life and poor tumor retention. This study aimed to develop a dual-functional self-assembled nanoplatform integrating PDT and selective uPA inhibition for synergistic CRC treatment. Methods: We designed and synthesized a conjugate by linking pyropheophorbide-a (PPA) with uPA-targeted cyclic peptide IG2, which self-assembled into nanoparticles (PINPs). Physicochemical properties, reactive oxygen species (ROS) generation, and uPA inhibitory activity were characterized. In vitro studies included cellular uptake, cytotoxicity, and invasion assays. In vivo therapeutic efficacy was evaluated in subcutaneous CT26 tumor models and lung metastasis models, with biosafety assessed by body weight monitoring. Results: PINPs exhibited uniform spherical nanostructure, prolonged blood circulation, and enhanced tumor accumulation via the enhanced permeability and retention (EPR) effect. Under 680 nm irradiation, PINPs generated robust ROS and induced tumor cell apoptosis. PINPs potently inhibited uPA activity and suppressed tumor cell invasion. In vivo, PINPs plus PDT achieved significant tumor growth inhibition (73.6%) and strong anti-metastatic efficacy (60.7%), superior to free IG2. No obvious systemic toxicity was observed. Conclusions: The dual-functional PINPs achieve short-term acute tumor ablation via PDT and sustained anti-metastatic potential via uPA inhibition within the tested observation windows, with favorable biosafety. This carrier-free self-assembly strategy provides proof-of-concept validation and a generalizable design paradigm for developing synergistic anti-metastatic nanotherapeutics against metastatic CRC. Full article

Glioblastoma (GB), the most prevalent and aggressive brain tumor, remains one of the most lethal challenges in modern oncology. Standard therapy remains largely ineffective, mainly due to limited therapeutic penetration across the blood–brain barrier (BBB) and adaptive tumor resistance. Consequently, there is an urgent need for innovative strategies to enhance therapeutic precision and efficacy. To address these limitations, we engineered a targeted peptide-based co-delivery system using the WRAP5 cell-penetrating peptide functionalized with a transferrin receptor (TfR)-targeting T7 peptide (sequence: HAIYPRH), enabling simultaneous delivery of temozolomide (TMZ) and a p53-encoding plasmid DNA. The resulting peptide-based TMZ/p53 nanocomplexes exhibited favorable physicochemical properties, enhanced TfR-mediated cellular uptake, and targeted antitumor activity mediated through p53-induced apoptosis in two-dimensional (2D) U87 MG cell cultures. To better reproduce the structural and cellular complexity of the tumor microenvironment, a three-dimensional U87 MG spheroid model was established and optimized using a Design of Experiments (DoE) approach to improve reproducibility and physiological relevance. The developed WRAP5-based nanocomplexes induced a significant dose-dependent inhibition of growth and morphological alterations in the U87 MG spheroid model, accompanied by deep penetration and cell death throughout the spheroid. Collectively, these findings highlight the potential of this targeted and tailored nanosystem to enhance cellular transfection, enable drug/gene co-delivery, restore p53 function, and promote apoptosis, representing a promising therapeutic strategy for GB treatment. Full article

Toad poison (ChanSu), a traditional animal-derived medicine, has long been used in East Asian medical systems for the treatment of inflammatory conditions and tumor-related disorders. While bufadienolides have been extensively investigated as its major bioactive constituents, the contribution of peptide components to its antitumor effects remains largely unexplored. Here, we identified protein-derived candidate antiproliferative peptides from toad poison using an integrated proteomics and bioinformatics-guided strategy. Proteomic analysis identified 135 proteins, from which 2117 peptide sequences were generated via in silico digestion with trypsin and pepsin. Subsequent multi-step screening using PeptideRanker, AntiCP, iACP, and ACPred yielded twelve candidate peptides with predicted anticancer activity. Network pharmacology analysis suggested their potential involvement in cancer-related targets and pathways. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) evaluation was subsequently used as a complementary assessment of drug-like and safety-related properties, further prioritizing four peptides for experimental validation, while molecular docking supported their interactions with key lung cancer-associated targets. In vitro assays demonstrated that three of the four prioritized peptides (WEAWN, NSQWG, and ACGVIGICQ) exhibited initial antiproliferative activity against human lung cancer A549 cells, though these findings should be interpreted with caution given the absence of a positive control in the MTT assay. This study provides preliminary evidence suggesting that protein-derived peptide candidates from toad poison may possess antiproliferative potential, representing an early systematic exploration of its previously unexplored peptidome as a source of candidate antiproliferative peptides warranting further pharmacological investigation. The integrated strategy presented here offers an efficient approach for the discovery of bioactive peptides from animal-derived traditional medicines. Full article