Search Results (4,981)

Background: Colorectal cancer (CRC) is characterized by pronounced genetic and phenotypic heterogeneity, which substantially influences therapeutic response and limits the efficacy of uniform treatment strategies. Cannabinoid-derived phytochemicals and boron-based compounds have independently been reported to modulate cancer cell proliferation, survival, and redox balance. However, the extent to which these agents interact at the cellular level and whether such interactions are dependent on tumor-specific molecular contexts remains poorly defined. Methods: Sodium pentaborate (NaB) was combined with non-cytotoxic concentrations of cannabidiol (CBD) or cannabigerol (CBG) and evaluated in HCT-116 and HT-29 colorectal cancer cell lines. Cell viability and drug interactions were assessed by MTS and combination index analyses. Apoptotic responses were examined by Annexin V/PI staining, caspase-3/7 activity assays, and transcriptional profiling of apoptosis-related genes. Cell cycle dynamics and proliferation-associated markers were analyzed by flow cytometry and quantitative PCR. In parallel, ferroptosis-associated gene expression patterns were investigated to evaluate alterations in redox and iron metabolism pathways. Results: NaB–cannabinoid combinations produced divergent biological outcomes depending on cellular background. HT-29 cells exhibited dose-dependent antiproliferative responses to NaB + CBD and NaB + CBG, with synergistic interactions observed only at selected dose combinations accompanied by increased early apoptosis. In contrast, HCT-116 cells primarily responded with cell cycle arrest and transcriptional stress signaling rather than enhanced cytotoxicity. Modulation of ferroptosis-related gene expression further indicated differential redox adaptation between the two cell models. Conclusions: NaB–cannabinoid combinations elicit distinct biological outcomes in colorectal cancer cells that are strongly determined by cellular context. While HT-29 cells are selectively sensitized to combination dose level, HCT-116 cells predominantly respond through cell cycle arrest and adaptive stress-response pathway activation. These findings emphasize the necessity of context-aware combination strategies and provide a mechanistic framework for the further development of boron–cannabinoid-based therapeutic approaches in colorectal cancer. Full article

Background: Ovarian cancer is frequently diagnosed at an advanced stage and remains one of the most lethal gynecologic malignancies. The development of multidrug resistance (MDR) during repeated chemotherapy is a major cause of treatment failure and is often associated with increased drug efflux mediated by transporters such as P-glycoprotein (P-gp). In this study, D-α-tocopheryl polyethylene glycol succinate (TPGS) and Soluplus^® (SOL) mixed micelles, abbreviated as TS, were developed to co-deliver apatinib (APA), a VEGFR-2 inhibitor, and etoposide (ETP), a topoisomerase II inhibitor, for MDR ovarian cancer models. The formulation was designed to improve the aqueous dispersion, cellular accumulation, and antitumor activity of APA and ETP. Methods: APA/ETP-loaded TS micelles (APA/ETP-mTS) were prepared and characterized in terms of particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), storage stability, and in vitro drug release. Anticancer efficacy was assessed using MTT assays, cellular uptake assays, and 3D tumor spheroid studies employing HeyA8-MDR cells, followed by in vivo toxicity and antitumor efficacy studies. Micellar formulations were denoted using the cargo–carrier format, where APA/ETP indicates co-loaded APA and ETP, C6 indicates coumarin-6 (C6) used as a fluorescent probe, mTS indicates TPGS/SOL mixed micelles, and mSOL indicates SOL-only micelles. Results: The selected APA/ETP-mTS formulation showed a particle size of 20.0 ± 5.1 nm, a PDI of 0.16 ± 0.05, near-neutral zeta potential, and encapsulation efficiencies exceeding 60% for both drugs. The micelles maintained colloidal stability at 4 °C for 4 weeks, although partial decreases in encapsulation efficiency were observed. Compared with APA/ETP solution, APA/ETP-mTS delayed the release of both drugs. C6-mTS showed higher intracellular fluorescence intensity than C6-mSOL, suggesting enhanced cellular accumulation associated with TPGS incorporation. APA/ETP-mTS showed greater cytotoxicity than free drugs in HeyA8-MDR monolayer cells and produced the strongest spheroid growth inhibition among the tested micellar formulations. In the HeyA8-MDR xenograft model, APA/ETP-mTS suppressed tumor growth and resulted in the lowest final tumor weight without apparent overt toxicity based on body weight and survival observations. Conclusions: These results suggest that APA/ETP-mTS is a promising micellar co-delivery platform for hydrophobic anticancer drugs in MDR ovarian cancer. Full article

Anthocyanin-rich preparations derived from bilberry (Vaccinium myrtillus L.) and blackcurrant (Ribes nigrum), whether standardized or otherwise analytically characterized, have been investigated for their potential to modulate chronic low-grade inflammation and oxidative stress. This narrative review focuses on human intervention studies using preparations explicitly derived from these species and contextualizes microbiota-related mechanisms and potential anticancer pathways using selected preclinical evidence. Human studies primarily report changes in inflammatory, endothelial, and oxidative-stress biomarkers, including hsCRP, IL-6, TNF-α, adhesion molecules, malondialdehyde, urinary 8-iso-PGF2α, and urinary 8-OHdG; however, findings are heterogeneous across formulations, doses, populations, intervention durations, and endpoints. Evidence for clinically meaningful outcomes remains limited. Studies of purified anthocyanins without unequivocal botanical sourcing are considered background evidence and are not used to substantiate species-specific claims. Mechanistically, intact anthocyanins have low systemic bioavailability, and colonic microbial metabolism generates phenolic metabolites that may interact with SCFA-related and barrier–immune pathways; however, causal relationships in humans remain insufficiently established. Potential anticancer mechanisms are supported predominantly by in vitro and animal studies and should therefore be considered hypothesis-generating rather than evidence of clinical efficacy. Overall, bilberry and blackcurrant preparations warrant further investigation in adequately powered, longer-duration human trials with transparent botanical characterization and clinically relevant endpoints. Full article

The hepatocyte growth factor (HGF)/c-Met signaling pathway plays a central role in cellular proliferation, survival, migration, invasion, angiogenesis, and therapeutic resistance. Aberrant c-Met activation, driven by gene amplification, overexpression, activating mutations, exon 14-skipping alterations, or ligand-dependent stimulation, drives the development and progression of many solid tumors, positioning c-Met as a key target for anticancer drug development. The clinical effectiveness of c-Met-targeted treatments such as crizotinib, capmatinib, tepotinib, savolitinib, and cabozantinib has confirmed c-Met as a viable oncogenic driver for therapy, leading to the development of various next-generation inhibitors with different structures. This review provides a comprehensive perspective on small-molecule c-Met inhibitors from the perspectives of medicinal chemistry and structure-based drug design, encompassing approved drugs, investigational agents, natural-product-inspired leads, and emerging multitarget anticancer therapeutics. Particular emphasis is given to the principles of molecular recognition that govern c-Met inhibition. This includes the structure of the kinase domain, interactions at the ATP-binding site, recognition of the hinge region, and the different binding modes of Type I, Type II, and allosteric inhibitors. The design, synthesis, biological evaluation, and structure–activity relationships of diverse heterocyclic scaffolds that have shaped c-Met inhibitor discovery are critically analyzed. Key medicinal chemistry strategies, including scaffold hopping, bioisosteric replacement, conformational optimization, molecular hybridization, and multitarget pharmacophore integration, are discussed in the context of potency, selectivity, resistance management, and drug-like properties. Particular attention is given to the integration of structural biology, molecular docking, binding-mode analysis, and structure-guided optimization approaches that have enabled the development of potent c-Met-directed inhibitors. In addition, recent advances in dual- and multitarget agents that simultaneously modulate c-Met and complementary therapeutic targets, including VEGFR-2, EGFR, AXL, MER, PARP1, CDK2, and tubulin, are highlighted as promising strategies for overcoming pathway redundancy and acquired resistance. This review summarizes contemporary structure-based and medicinal chemistry principles underlying c-Met inhibitor discovery, critically evaluates the relationship between biochemical potency and therapeutic efficacy, and provides a framework for the rational design of next-generation c-Met-targeted and multitarget anticancer agents. Full article

Resveratrol (RSV) is a naturally occurring polyphenol with well-documented antioxidant, anti-inflammatory, antimicrobial, photoprotective, wound-healing, depigmenting, and anticancer properties, making it an attractive candidate for dermocosmetic and dermatological applications. However, its clinical translation into effective topical products remains limited by poor aqueous solubility, chemical instability, photoisomerization, rapid cutaneous metabolism, and restricted skin penetration, all of which compromise local bioavailability and therapeutic efficacy. This narrative review critically examines the molecular mechanisms underlying the cutaneous effects of RSV and discusses how its physicochemical and pharmacokinetic characteristics influence topical performance. Particular emphasis is placed on advanced delivery strategies developed to overcome these limitations, including lipid-based nanocarriers, polymeric nanoparticles (NPs), nanofibers, inorganic nanocarriers, microneedles, hydrogels, and other emerging delivery platforms. The mechanisms by which these systems improve RSV solubility, stability, controlled release, skin retention, and dermal penetration are critically evaluated together with their reported therapeutic outcomes. Although advanced delivery systems have consistently improved the topical performance of RSV in preclinical studies, clinical evidence remains limited. To date, only one published placebo-controlled clinical trial has specifically evaluated topical RSV as the active ingredient, and none of the advanced RSV-nanocarrier platforms discussed in this review has undergone clinical evaluation. Bridging this substantial translational gap will require not only further optimization of formulation design but also scalable manufacturing, rigorous clinical validation, and regulatory pathways capable of supporting the development of safe, effective and evidence-based next-generation dermocosmetic and dermatological products. Full article

Nutritional therapy is an essential component of comprehensive care for cancer patients, playing a vital role in preventing malnutrition, improving treatment tolerance, and maintaining quality of life. In recent years, there has been growing interest in the ketogenic diet as a potential strategy to support cancer therapy. This diet, based on a significant reduction in carbohydrate intake and an increase in fat intake, leads to a state of ketosis that mimics the metabolic changes that occur during starvation. Consequently, the body utilizes ketone bodies as an alternative source of energy. The potential application of the ketogenic diet in oncology stems from the distinct metabolism of cancer cells, which often exhibit an increased demand for glucose. Although the results of preclinical studies suggest a possible anticancer effect of this dietary intervention, clinical evidence remains limited, and its routine use is not currently recommended as a standard of care in oncology. The aim of this study was to analyze the current literature on the use of the ketogenic diet in oncology, with a particular focus on breast cancer. The study assessed the impact of this intervention on metabolic parameters, body composition, and patients’ mental well-being, and analyzed the potential metabolic risks associated with its use. The study discusses the molecular basis of oncogenesis and metabolic adaptation in cancer cells, the mechanisms of action of the ketogenic diet, and the results of preclinical and clinical studies as well as meta-analyses. Importantly, the current evidence base should be interpreted with caution. Most mechanistic evidence supporting ketogenic diet in breast cancer derives from preclinical models, whereas clinical studies remain limited by small sample sizes, short intervention periods, heterogeneous ketogenic diet protocols, substantial attrition, and differences in concomitant anticancer treatment. Therefore, mechanistic plausibility and promising preclinical findings should not be interpreted as evidence of clinical anticancer efficacy. Full article

Glioblastoma (GBM) is a highly aggressive brain tumor with limited therapeutic options due to its invasive nature, therapeutic resistance, and the challenge of drug delivery across the blood–brain barrier (BBB). Mesenchymal stem cells (MSCs), owing to their tumor tropic properties and ability to cross the BBB, offer a promising platform for targeted anti-cancer delivery. We previously engineered MSCs to express CD::UPRT and TRAIL, along with chemokine receptors to enhance tumor homing (MSC-CD-TRAIL; BM03). This study evaluated the anti-tumor efficacy of BM03 using GBM patient-derived organoids (GBOs), clinically relevant in vitro models. Using a GBO–MSC co-culture system, BM03 significantly increased cell death and reduced viability in GBOs from four GBM patients compared with controls and MSC-WT groups. In 3D invasion assays, BM03-treated GBOs showed markedly reduced invasive outgrowth, accompanied by downregulation of EMT markers (Zeb1 and Snail) and stem-like markers (Olig2 and Sox2), particularly in invasive regions. GFAP expression remained unchanged, suggesting selective targeting of tumor stem-like cells. Live-cell imaging further demonstrated BM03 infiltration into GBOs, which was associated with increased apoptosis, as evidenced by elevated cleaved caspase-3 levels. These findings provide organoid-based preclinical evidence supporting further evaluation of BM03 as an MSC-based therapeutic strategy for GBM. Full article

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor clinical outcomes and limited responsiveness to conventional treatments. Beyond delayed diagnosis, its high mortality is linked to limited treatment choices and resistance to chemotherapy. Neoplastic cells characterized by stem-like features and epithelial–mesenchymal transition (EMT) activation are crucial drivers of drug resistance and metastatic progression. Consequently, targeting these cellular programs could represent a promising therapeutic strategy for PDAC. N-acetyl-L-aspartic acid (NAA) is an endogenous metabolite, mainly localized in the central nervous system, where it facilitates acetate storage for lipid metabolism. Previous studies established its antineoplastic effect in neuroblastoma, promoting a more differentiated phenotype of cancer cells. Here we investigated the effects of NAA on BxPC-3 pancreatic cancer cells using both 2D and 3D models. NAA treatment induced a dose-dependent reduction in cell proliferation and led to a significant downregulation of stemness-associated surface markers, with concomitant upregulation of E-cadherin. Furthermore, NAA significantly enhanced cellular radiosensitization with a reduction in caveolin-1 and increased efficacy of gemcitabine in PDAC cells. Collectively, these results confirmed the anticancer activity of NAA and provide a rationale for further investigation of its synergistic effects with radiotherapy to yield better PDAC treatments. Full article

Cancer is still one of the major causes of death globally. While there are many cancer therapies, they often come with significant adverse effects and limitations. A lot of studies have shown that using natural products can improve the efficacy of conventional therapies and decrease their toxicity. Natural products and their derivatives encompassing unmodified molecules, semi-synthetic analogs, and synthetic structures featuring natural pharmacophores, represent a major foundation for approved anticancer agents. Phenolic compounds are a large family of naturally occurring compounds found in plants and have attracted a lot of attention for their potential anticancer properties. Preclinical studies have shown that phenolic compounds have anticancer activity through different mechanisms, mainly by modulating inflammation, which plays a critical role in cancer development. Inflammatory processes in cancer involve complex molecular mechanisms regulated by both oncogenic and tumor-suppressing transcription factors. This review focuses on how phenolic compounds regulate transcription factors, such as nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and signal transducer and activator of transcription 3 (STAT3), which are critical in cancer-related gene expression, ultimately leading to the inhibition of cancer cell proliferation, invasion, and metastasis. Furthermore, phenolic compounds have been shown to synergize with conventional anticancer drugs, enhancing their efficacy and reducing side effects. This review investigates the role of phenolic compounds in regulating transcription factors in cancer animal models, highlighting both the therapeutic potential and limitations of these compounds in cancer prevention and treatment. Full article

Background/Objectives: Oxidative stress, chronic inflammation, disrupted apoptosis, and altered autophagy are biological processes implicated in colorectal tumor development. Morin is a plant-derived flavonoid with antioxidant and anti-inflammatory properties, but its limited solubility and bioavailability may limit its biological activity. This study evaluated the effects of free morin and morin-loaded liposomes (MOR-Lips) on 1,2-dimethylhydrazine (DMH)-associated colonic biochemical, molecular, and histopathological alterations in rats. Methods: Rats were randomly assigned to six groups—vehicle control, MOR, MOR-Lips, DMH, DMH + MOR, and DMH + MOR-Lips—and treated for 10 weeks. Serum and colonic tissues were evaluated for cancer-associated biomarkers (CEA, CA19-9, CA125, HMG-CoA reductase), oxidative stress and antioxidant indices, nitrosative and oxidative DNA-damage markers (MDA, NO, 8-OHdG), inflammatory mediators (TLR4/NF-κB/COX-2, cytokines, MPO), proliferative indices (Ki-67, PCNA), apoptotic and autophagy-related regulators (Bax, caspase-3, p53, cytochrome c, BCL-2, p-AKT, LC3-II, Beclin-1, p62), and histopathological and immunohistochemical changes. Results: DMH exposure was associated with increased CEA, CA19-9, CA125, HMG-CoA reductase, MDA, NO, 8-OHdG, TLR4/NF-κB/COX-2, cytokines, MPO, Ki-67, and PCNA. DMH also reduced NRF2/HO-1 signaling and antioxidant defenses, shifted apoptosis-related markers toward a pro-survival profile, altered autophagy-related markers, and produced marked colonic histopathological abnormalities. Both free MOR and MOR-Lips attenuated several of these DMH-associated alterations, with MOR-Lips generally producing greater effects than free MOR. MOR-LIP treatment was associated with restoration of antioxidant marker profiles, reduced levels of inflammatory and proliferative markers, a shift toward a pro-apoptotic marker profile, partial normalization of autophagy-related markers, and improved colonic histopathological appearance. Conclusions: In DMH-exposed rats, MOR-Lips were associated with more favorable redox, inflammatory, proliferative, apoptosis-related, autophagy-related, and histopathological profiles than free MOR. These findings support further investigation of MOR-Lips as a formulation strategy for improving the biological activity of morin. Because quantitative preneoplastic and neoplastic endpoints were not measured, the results do not establish inhibition of colorectal carcinogenesis or chemopreventive efficacy. Full article

Cancer nanomedicine has generated extensive preclinical evidence of improved drug delivery, pharmacokinetics, and tolerability, yet its clinical impact has often remained modest. This narrative review examines the interconnected biological, pharmacokinetic, manufacturing, regulatory, and clinical factors underlying this translational paradox. A structured literature search was conducted primarily in PubMed and Google Scholar, focusing on studies published between 2022 and 2026 while retaining seminal earlier reports. Major biological barriers include protein corona formation, mononuclear phagocyte system clearance, heterogeneous enhanced permeability and retention, complex tumor microenvironments, and intratumoral heterogeneity. These factors limit circulation, tumor accumulation, tissue penetration, drug release, and interpatient reproducibility. Translation is further constrained by off-target accumulation, uncertain long-term toxicity, non-standardized experimental methods, batch-to-batch variability, scale-up challenges, and fragmented regulatory pathways. Clinical experience shows that successful products are dominated by relatively established platforms and reformulations of known anticancer agents, whereas many actively targeted or structurally complex systems have failed to demonstrate sufficient efficacy or safety. Future progress will require mechanism-driven design, human-relevant preclinical models, harmonized characterization, quality-by-design manufacturing, early regulatory integration, biomarker-guided patient selection, and adaptive clinical trials. Aligning nanoparticle engineering with biological and clinical realities is essential for achieving meaningful patient benefit. Full article

Population aging has intensified the search for natural compounds capable of promoting healthy aging and preventing age-related diseases. Among medicinal plants, species of the genus Crataegus (hawthorn) have attracted increasing attention because of their rich phytochemical composition and broad spectrum of biological activities. This review summarizes and critically evaluates current evidence on the geroprotective potential of Crataegus species, integrating data from phytochemical, pharmacological, and mechanistic studies. Particular attention is given to the major bioactive constituents of Crataegus, including flavonoids, oligomeric proanthocyanidins, phenolic acids, and triterpenoids, which exhibit antioxidant, anti-inflammatory, cardioprotective, neuroprotective, metabolic, and anticancer properties. We discuss the growing evidence that these phytochemicals target multiple hallmarks of aging by modulating oxidative stress, chronic low-grade inflammation (inflammaging), mitochondrial dysfunction, cellular senescence, and the senescence-associated secretory phenotype (SASP). Their biological effects are mediated through key signaling pathways involved in cellular homeostasis and longevity, including Nrf2/ARE, NF-κB, PI3K/Akt/mTOR, AMPK, and SIRT1. The review also critically examines findings from in vitro, in vivo, and available clinical studies, highlighting both the therapeutic potential and current limitations of Crataegus-based interventions for age-related disorders. Although preclinical evidence strongly supports the multi-target geroprotective properties of Crataegus species, clinical validation remains limited. Overall, Crataegus represents a promising source of natural geroprotective agents with the potential to promote healthy aging through the modulation of multiple aging-related molecular pathways. Future well-designed clinical studies are essential to establish their efficacy, safety, optimal dosage, and long-term therapeutic value in humans. Full article

Doxorubicin (DOX) is an antineoplastic agent commonly used in cancer therapy that is known for its testicular toxicity. DOX-induced testicular injury involves inflammation, reactive oxygen species, and oxidative stress. Centella asiatica exhibits anti-inflammatory and antioxidant properties. The present experimental study aimed to determine the potential protective efficacy of Centella asiatica in a rat model of doxorubicin-induced testicular toxicity. Rats were randomly assigned to four groups: healthy control (HC), CA, DOX, and CA + DOX (CADX). An oral dose of 200 mg/kg Centella asiatica was administered to the CA and CADX groups. The HC and DOX groups received saline. One hour later, DOX (7.5 mg/kg) was intraperitoneally injected into the DOX and CADX groups on days 1, 4, and 7. Centella asiatica markedly attenuated the DOX-induced increase in malondialdehyde, nitric oxide, and pro-inflammatory cytokine levels, while preventing the decrease in superoxide dismutase activity in testicular tissue (p < 0.001). Centella asiatica reduced the severity of DOX-induced morphological damage in testicular tissue (p < 0.05). Moreover, it partially restored reproductive hormone function. In conclusion, Centella asiatica demonstrates significant potential in mitigating DOX-induced oxidative damage, attenuating testicular injury and preserving the functional integrity of the male reproductive system. Full article

Oral squamous cell carcinoma (OSCC) remains a clinically challenging malignancy because of recurrence, treatment resistance, and limited therapeutic efficacy in advanced disease. This study investigated the anticancer effects and molecular mechanisms of jaceidin (JAC), a naturally occurring flavonoid derivative, in human OSCC cells. SCC-1 and SCC-47 cells were treated with JAC, and cell viability, colony formation, cell cycle distribution, apoptosis, and apoptosis-related signaling pathways were examined. JAC reduced OSCC cell viability and colony formation in a dose- and time-dependent manner. It also induced G2/M cell cycle accumulation and decreased the expression of cyclin D1, cyclin E1, phosphorylated cdc2, and CDK2/4/6. Apoptosis analyses showed that JAC promoted caspase-dependent apoptotic signaling, as evidenced by increased cleavage of caspase-3, caspase-8, caspase-9, and PARP. JAC modulated death receptor-associated signaling, characterized by increased Fas, TRADD, and DR5 expression and caspase-8 cleavage, while the decoy receptors DcR2 and DcR3 were also upregulated. JAC also promoted mitochondrial apoptotic signaling by increasing Bax, Bak, and Bim expression while decreasing Mcl-1. In addition, JAC attenuated AKT and ERK1/2 phosphorylation, and pharmacological inhibition with LY294002 or U0126 further enhanced JAC-induced apoptotic signaling. Furthermore, JAC reduced survivin expression and attenuated survivin-mediated apoptotic resistance. These findings suggest that JAC suppresses OSCC cell survival in association with modulation of AKT/ERK–survivin signaling and caspase-dependent apoptosis. Full article

Cancer therapy-related cardiotoxicity has emerged as a major challenge in contemporary oncology, particularly in long-term survivors of childhood malignancies. Oxidative stress (OS)-induced cardiotoxicity represents a key mechanistic pathway underlying myocardial injury caused by numerous anti-neoplastic drugs, most notably anthracycline-based chemotherapy, while OS also critically contributes to radiotherapy-induced cardiotoxicity. Excessive reactive oxygen and nitrogen species generation promotes mitochondrial dysfunction, impaired calcium homeostasis, lipid peroxidation, endothelial injury, inflammatory activation, and cardiomyocyte apoptosis, ultimately leading to progressive cardiac remodeling and ventricular dysfunction. These processes are of particular concern in pediatric cancer survivors, especially children treated for leukemia, who face a substantially elevated lifetime risk of cardiovascular disease following treatment exposure. Increasing attention has, therefore, been directed toward nutritional strategies capable of modulating redox homeostasis and attenuating treatment-associated myocardial injury. Experimental and translational evidence suggests that selected dietary compounds and nutraceuticals, including polyphenols, omega-3 fatty acids, coenzyme Q10, selenium, antioxidant vitamins, nutrition-based epigenetic interventions and intestinal microbiota composition modulations may exert cardioprotective effects through preservation of mitochondrial integrity, enhancement of endogenous antioxidant defenses, and suppression of oxidative and inflammatory signaling pathways. Nevertheless, clinical implementation remains limited by insufficient standardization, heterogeneous study designs, and incomplete understanding of long-term efficacy and safety. This narrative review critically examines the molecular basis of the OS-induced cardiotoxicity and radiotherapy-induced cardiotoxicity and evaluates current evidence supporting nutrition-based cardioprotective interventions, with particular emphasis on pediatric leukemia survivors and the prevention of long-term cardiovascular complications following anticancer therapy. Full article