Cancer is a medical problem that has been difficult to overcome on a global scale. Owing to the sharing of single or multiple genes or regulatory modules, cancer treatment often faces severe challenges. The core of network pharmacology lies in constructing human disease gene regulation networks and multi-pharmacology network. With the continuous updating and iteration of new technologies, it is helpful for us to systematically understand the occurrence and development mechanism behind complex diseases and elucidate the pharmacological mechanisms from the perspective of biological network balance. This review aims to clarify the application of network pharmacology in exploring the pharmacological treatment mechanism of natural products, drug repositioning, and new technology combinations in the context of complex pathogenesis of cancer, so as to help realize the full potential of network pharmacology. Additionally, we discuss the future development of network pharmacology to guide clinical diagnosis and treatment.

Immune-related neuropathy (irNeuropathy) and myositis (irMyositis) are the most common neurologic adverse events (irAE-n) associated with immune checkpoint inhibitors. Although case reports suggest benefits of complement inhibitors, the role of complement activation in irAE-n is understudied.

For patients with advanced non-small cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor (EGFR) mutations, guidelines prioritize the use of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), which offer higher objective response rate (ORR), longer progression-free survival (PFS), and better quality of life. However, due to the low proportion of elderly patients enrolled in clinical trials, the existing evidence is insufficient to fully guide clinical practice. This review examines the efficacy and safety differences of third-generation EGFR-TKIs as monotherapy or in combination in the elderly NSCLC by integrating subgroup analyses or pre-specified research objectives from prospective and retrospective studies. The results show that third-generation EGFR-TKIs have comparable efficacy in elderly patients to younger populations and are well-tolerated. Although combination therapies may extend survival time, the associated increased toxicity necessitates careful risk-benefit assessment.
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The cardiotoxicity of immune checkpoint inhibitors (ICIs) has garnered significant clinical attention due to its high mortality rate. However, limited clinical research and inconsistent results have hindered a comprehensive understanding of this issue. This study seeks to elucidate gender and age differences in cardiac-related adverse reactions, aiming to offer scientific evidence to inform clinical practice.

Resistance to v-raf murine sarcoma viral oncogene homolog B1 (BRAF) plus mitogen-activated protein kinase kinase (MEK) inhibition (BRAFi+MEKi) in BRAFV600E-mutant gliomas drives rebound, progression, and high mortality, yet it remains poorly understood. This study addresses the urgent need to develop treatments for BRAFi+MEKi-resistant glioma using preclinical mouse models and patient-derived materials. BRAFi+MEKi reveals glioma plasticity by heightening cell state transitions along glial differentiation trajectories, giving rise to astrocyte- and immunomodulatory oligodendrocyte (OL)-like states. PD-L1 upregulation in OL-like cells links cell state transitions to immune evasion, possibly orchestrated by Galectin-3. BRAFi+MEKi induces interferon response signatures, tumor infiltration, and suppression of T cells. Combining BRAFi+MEKi with immune checkpoint inhibition enhances survival in a T cell-dependent manner, reinvigorates T cells, and outperforms individual or sequential therapies in mice. Elevated PD-L1 expression in BRAF-mutant versus BRAF-wild-type glioblastoma supports the rationale for PD-1 inhibition in patients. These findings underscore the potential of targeting glioma plasticity and highlight combination strategies to overcome therapy resistance in BRAFV600E-mutant high-grade glioma.

Immune checkpoint inhibitor (ICI) have demonstrated efficacy in treating various cancers by modulating the immune system, but this can lead to immune-related adverse events (irAEs), including myocarditis. ICI-associated myocarditis is a rare but highly lethal irAE with a short mean time to onset, and difficult to diagnose early due to nonspecific symptoms and lack of biomarkers. This review highlights the need for improved recognition and management of ICI-associated myocarditis, summarizing recent advances in immunology, pathology, and biomarker research. We discuss the epidemiology, clinical features, immunological mechanisms, and roles of biomarkers in diagnosis and risk stratification. Traditional biomarkers like cTnI and hs-cTnT are sensitive but lack specificity, while emerging biomarkers like miR-155 show tissue specificity. Inflammatory markers such as NLR and CRP aid prognosis but have limited diagnostic value.

Glioblastoma is the most predominant type of brain tumor, and resistance to medication has hampered the effectiveness of chemotherapy for gliomas. Acyclic monoterpene alcohol, linalool, has a range of pharmacological properties. The present study aimed to evaluate the impact of linalool and its nanoformulation on glioblastoma cell proliferation. DFT and ADMET analyses were used to initially assess the physiochemical characteristics of linalool and the produced silver nanoconjugates, LN@AgNPs. STRING database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to narrow the 6 genes involved in glioblastoma and underwent for molecular docking study. Using AutoDock Vina 1.5.7, ligands were docked to the interaction site of selected targets. Top scored complexes PD-L1/Ligands and PTEN/ligands were simulated using molecular dynamics. The results revealed that LN@AgNPs produced a more stable complex, because metallic bonds are more robust and durable than hydrogen bonds, which give metals their distinctive strength and stability. To confirm the cytotoxicity of the compound against GBM cell line SF-767, linalool and LN@AgNPs were evaluated by in vitro study to check the expression at the IC50 concentration of top scored selected genes. The results indicated that the cytotoxic effects of linalool and LN@AgNPs were concentration dependent. In the SF-767 cancer cell line, linalool and LN@AgNPs with IC50 (33.14 µg/mL and 22.12 µg/mL respectively) values downregulated PD-L1 expression and increased PTEN expression. In conclusion phytocompounds conjugated with AgNPs increased cytotoxicity and inhibition index in glioblastoma cells. Therefore, LN@AgNPs may be a viable option for cancer treatment.

Nigella sativa L. widely used spice cum medicinal plant in Asia and the middle east, is renowned for its seeds and oil which possess both culinary and therapeutic purposes. Its rich content of bioactive compounds, including metabolites and phenolics, with Thymoquinone, a monoterpene quinone, emerging as key therapeutic compound significantly consideration for its various pharmacological activity with lower toxicity compared to conventional chemotherapy. This study evaluated the anticancer potential of thymoquinone isolated from N. sativa L., through cytotoxicity and In Silico studies. Seeds from 38 accessions were collected across the country and screened for Thymoquinone content using HPTLC with the highest concentration identified in Ajmer Nigella 13 (247.60mg 100gm-1) accession. In Vitro MTT assay of Thymoquinone in human myelogenous leukemia (K562) cells demonstrated significant dose and time dependent cytotoxicity confirming Thymoquinone's potential as a promising therapeutic candidate for leukemia and other cancer.

Narrow therapeutic indices of chemotherapeutic agents necessitate precise dosing to ensure efficacy and minimize nephrotoxicity. Due to the complexity of directly measuring Glomerular filtration rate (GFR), renal dosing is usually based on GFR estimation equations. The Cockcroft-Gault formula remains the most widely used equation in cancer patients, despite the availability of more precise kidney function estimation equations. Therefore, the aim of the study was to assess the agreement between Cr and cystatin-C (CysC) based GFR estimation equations and GFR estimated by Cockcroft-Gault for appropriate chemotherapy dosing in cancer patients undergoing assessment for first-Line chemotherapy at an oncology unit of St. Paul's Hospital Millennium Medical College in Ethiopia.

Vitamin E can exert either a cancer preventive effect or improve the therapeutic efficacy of chemotherapeutic drugs against multiple types of cancer. Ample evidence suggests that the cancer preventive activity of vitamin E is form-dependent; however, it is not clear whether its chemosensitization effect is also influenced by its forms. The objectives of this study were to investigate whether the eight natural forms of vitamin E produced differential sensitization effects on cancer chemotherapeutic drugs and to address whether the chemosensitization effect of vitamin E was associated with its inhibitory effect on programmed cell death ligand 1 (PD-L1) signaling. We carried out a comparative evaluation of the chemosensitization effect of eight vitamin E forms using paclitaxel as a representative therapeutic drug and breast/prostate cancer as the representative types of cancer. Results showed that the sensitization effect of vitamin E on chemotherapeutic drugs was also form-dependent, with δ-tocotrienol (δ-T3) as the most effective one for sensitizing breast and prostate cancer cells to paclitaxel, mechanistically associated with its ability to suppress PD-L1-mediated tumor-promoting signaling. The findings provided novel insights into understanding the sensitization effect of vitamin E and its related mechanisms and support that δ-T3 is the best candidate as an enhancer of taxanes among the eight forms.

IntroductionThe Cancer and Aging Research Group (CARG) model predicts chemotherapy-related toxicities in older patients; however, its applicability has not been validated in Taiwanese patients. This study aims to validate the CARG model in older Taiwanese patients with solid tumors.MethodsPatients (N = 258) aged ≥65 years with solid tumors from a single medical center, slated for first-line chemotherapy, were recruited between 2018 and 2021, with follow-up until December 31, 2022. Patients were categorized into low- (N = 85), medium- (N = 117), and high- (N = 56) risk based on CARG. Validation of CARG involved receiver operating characteristic (ROC) curves. Individual CARG variables were analyzed using univariate analysis for their impact on toxicities and survival.ResultsToxicities of grades ≥3 were 38.8%, 44.4%, and 67.9% (P = .001) in the three ascending risk groups, and there were significant differences in both hematological (P = .002) and non-hematological (P < .001) toxicities. ROC was 0.631 (95% CI: 0.562-0.700), indicating satisfactory discrimination. One-year overall survival rates were 88.7%, 79.7%, and 63.8%, respectively, in ascending-risk groups, with high-risk groups showing decreased survival (P = .002). In the multivariate analysis, decreased hemoglobin, history of falls, and inability to walk one block remained significantly associated with toxicity. For overall survival, the inability to take medications was the only independent predictor.ConclusionThis prognostic study validated the CARG model in a heterogeneous solid tumor cohort in Taiwan. In addition to predicting both hematological and non-hematological toxicities, CARG could offer insights into patient survival among older individuals with cancer.

Hepatocellular carcinoma (HCC) remains a major global health challenge, with limited efficacy of current immunotherapeutic strategies. Immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns (DAMPs), offers a promising approach to enhance antitumor immunity. Arsenic trioxide (ATO), an ICD inducer, may synergize with PD-1 inhibitors to overcome therapeutic resistance, though the underlying mechanisms remain unclear.

Diarrhea is primary adverse effect of capecitabine (Cap) causing treatment discontinuation. The aim of this study was to construct an early-warning model for predicting the Cap-induced diarrhea.

Azithromycin is a member of macrolide antibiotics, and has been reported to inhibit the proliferation of cancer cells. Nanoparticles particularly nanometals have been recently investigated in cancer chemotherapy owing to their enhanced pharmacokinetic and pharmacodynamic profile over conventional preparations due to nanoscale size and unique physicochemical characteristics. Therefore, this study is intended to explore the role of silver and gold metallic form of an antibiotic Azithromycin (AZM) in exhibiting the anticancer activity against hepatocellular carcinoma cell line (HepG2). After synthesis, Azithromycin conjugated gold and silver nanoparticles were characterized by UV-visible spectroscopy, Fourier transform infrared analysis, Atomic force microscopy and Zeta sizer and zeta potential analysis. HepG2 cells treated with Azithromycin, Gold conjugated Azithromycin (Au-AZM) and Silver conjugated Azithromycin (Ag-AZM) were analyzed for cytotoxic activity via MTT assay and apoptotic potential via nuclear area factor calculation made after processing DAPI stained images. The cytotoxicity data showed that Silver conjugated Azithromycin showed more inhibitory effect (IC50= 33.3µg/ml) on proliferation of HepG2 cells as compared to Gold conjugated Azithromycin (IC50= 78.3µg/ml) and Azithromycin alone (IC50=88.8µg/ml) respectively. Similarly, the Silver conjugated Azithromycin group showed enhanced apoptosis in comparison with Gold conjugated Azithromycin and Azithromycin. In conclusion, this study proposes a potent role of Silver conjugated Azithromycin in attenuation of hepatocellular cancer cell growth, nevertheless further in vivo and clinical trials are required in order to mark its significance as a therapeutic agent.

It has been hypothesized that inflammation and oxidative stress have a potential role in neurodegeneration. Cisplatin is a commonly used in different types of cancers but it is notorious for oxidative stress which leads to neurodegeneration. Therefore, the current study focused on the antioxidant effect of Calotropis procera during cisplatin treatment. The methanolic extract of C. procera was extracted using rotary evaporator. Memory impairment was evaluated by using Y-Maze and Morris water model. The antioxidant effect of C. procera extract was measured by assessing oxidative stress markers such as lipid peroxidation (LPO), reactive oxygen species (ROS), glutathione (GSH), and catalase (CAT) in the experimental groups. It has been found that C. procera extract showed a significant (p<0.05) effect on preventing memory dysfunction compared to a positive control (cisplatin). The effect of C. procera extract was observed in a dose-dependent manner. Similarly, the increase (p<0.05) in the level of oxidative stress marker was high compared to the positive control group in a dose-dependent manner. While the decrease in the level of malondialdehyde (MDA) was found in the C. procera extract treated groups dose-dependently. C. procera significantly reduces cisplatin-induced oxidative stress by restoring the level of antioxidant enzymes and reducing MDA levels. The therapeutic benefits are significant at a dose of 400 mg/kg.

Amaranthus spinosus is a medicinal plant with notable pharmacological properties. In the present work, silver nanoparticles (AgNPs) were synthesized using methanolic leaf extract of A. spinosus. The synthesis of AgNPs was indicated by a color change from green to brown and confirmed through UV-Vis spectroscopy, FTIR, SEM, and XRD analyses. The XRD peaks between 20° and 50° confirmed the crystalline nature of AgNPs, while SEM (1 μm scale) revealed uniformly distributed spherical nanoparticles below 100 nm. The AgNPs exhibited potent antimicrobial activity, with the highest inhibition observed against Klebsiella pneumoniae (20 mm at 100 μg), surpassing the plant extract. Antioxidant assays proved the free radical scavenging capacity of AgNPs compared with standard ascorbic acid. At 500 μg/mL, AgNPs achieved 71% DPPH scavenging, 75% hydroxyl radical scavenging, and 68% reducing power, significantly outperforming the plant extract. The in vitro anticancer property of AgNPs against HT-29 colorectal cancer cells revealed a concentration-dependent cytotoxic effect, with maximum cell death at 100 μg/mL. AO/EtBr staining confirmed apoptosis through a shift from green to orange/red fluorescence, while DAPI staining indicated nuclear condensation and fragmentation. These findings highlight A. spinosus-derived AgNPs as promising candidates for biomedical applications, offering enhanced antimicrobial, antioxidant, and anticancer properties via eco-friendly synthesis.

Dauriporphine is a major ingredient of Manispernum daericum DC., which has been demonstrated to show wide anti-tumor activities. miR-424-5p, as a regulator of lung cancer, was hypothesized to serve as the therapeutic target for dauriporphine This study evaluated the potential of dauriporphine in treating lung adenocarcinoma and revealed the underlying molecular mechanism.

Regarding their distinct physico-chemical and bioactivity characteristics, silver nanoparticles 'AgNPs' are extensively utilized in numerous scientific purposes.

Procyanidins (PCs), dietary polyphenols found in fruits, vegetables, and beverages, exhibit potent anticancer properties. Their mechanisms of action involve modulating oxidative stress, inhibiting angiogenesis, inducing apoptosis, and preventing tumor progression. Despite promising preclinical and clinical findings, their therapeutic potential remains underexplored. This review aims to provide a comprehensive analysis of the anticancer properties of PCs, including their bioavailability, pharmacokinetics, and safety. A systematic literature search was conducted across databases such as PubMed, Scopus, and Web of Science, utilizing Medical Subject Headings (MeSH) terms and specific keywords. Studies were selected based on predefined inclusion criteria, focusing on in vitro, in vivo, and clinical evidence. PCs demonstrate anticancer effects through multiple pathways, including inhibition of pro-inflammatory cytokines, suppression of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways, and regulation of apoptosis-related proteins such as BCL2-associated X protein (BAX), B-cell lymphoma 2 (BCL-2), and caspases. PCs demonstrate anticancer effects through multiple pathways, including inhibition of pro-inflammatory cytokines, suppression of the PI3K/AKT/mTOR and MAPK/ERK pathways, and regulation of apoptosis-related proteins such as BAX, BCL-2, and caspases. However, their low oral bioavailability and metabolic instability pose challenges for clinical application. Current research highlights the need for novel delivery systems, such as nanoparticles and liposomes, to enhance systemic absorption and therapeutic efficacy. Ongoing clinical trials are investigating the potential of PCs as adjuvants in cancer therapy, either alone or in combination with chemotherapeutic agents. Future studies should focus on optimizing their pharmacokinetics, exploring synergistic effects with existing treatments, and conducting large-scale clinical trials to validate their efficacy and safety. PCs hold promise as natural anticancer agents, with the potential to complement conventional therapies and improve patient outcomes.

Angiogenesis plays a critical role in cancer progression, highlighting the need for effective anti-angiogenic therapies. Zerumbone (ZER), a phytochemical compound, is known for its anti-angiogenic and anti-carcinogenic effects in various cancer cell lines. Cisplatin (CIS) is a widely used chemotherapeutic agent that effectively inhibits tumor growth. Combining CIS with anti-angiogenic agents like ZER may enhance the anticancer efficacy of CIS and improve treatment outcomes. This study aimed to evaluate the acute toxicity and anti-angiogenic effects of ZER, CIS, and the ZER + CIS combination in a zebrafish larval model. At higher concentrations, the ZER + CIS combination demonstrated only minimal toxicity. Both CIS and ZER exhibited significant anti-angiogenic activity, as indicated by the depletion of o-dianisidine-positive red blood cells in circulation compared to the control. The combination of ZER and CIS synergistically enhanced the down-regulation of VEGF-A (p < 0.001), VEGFR-2, NRP-1A, and NRP-2B, confirming the synergistic action of the two compounds. In conclusion, the combination of ZER and CIS exhibited superior anti-angiogenic effects compared to either treatment alone, suggesting a promising therapeutic strategy for cancer treatment.