Recent patents on anti-cancer drug discovery最新文献

Introduction: Liver cancer remains one of the most aggressive and lethal malignancies worldwide，and current therapeutic efforts show limited survival benefits. Based on our previous findings that aucubin attenuates liver ischemia-reperfusion injury by inhibiting the HMGB1/TLR-4/NF-κB signaling pathway, this study aimed to elucidate the biological functions and molecular mechanisms of aucubin in liver cancer.

Methods: In this study, the role of aucubin in liver cancer was examined using liver cancer cell models and tumor-bearing mouse models. We evaluated whether the anti-tumor effect of aucubin is dependent on HMGB1 and its key signaling pathways. Intellectual property implications related to this small molecule are also explored.

Results: Results revealed that aucubin effectively reduced the Epithelial-Mesenchymal Transition (EMT) behavior of liver cancer in nude mice and inhibited the migration and invasion ability of liver cancer cells. The effect of aucubin on migration and proliferation was reversed by HMGB1 overexpression in HepG2 and HCCLM3 cells. Aucubin inhibited the levels of HMGB1, RAGE, p-PI3K, p-AKT, and p-mTOR proteins in mouse tumor tissues and this change was reversed by HMGB1 overexpression.

Discussion: We identified that aucubin exerts anti-liver cancer effects. By investigating the regulatory effects of HMGB1 overexpression and AKT agonist SC79 intervention on the HMGB1/ RAGE axis and PI3K/AKT/mTOR pathway, our findings confirmed the core role of the HMGB1/RAGE axis in aucubin's anti-tumor activity, as well as aucubin's regulation of liver cancer cell proliferation, migration, and invasion via the PI3K/AKT/mTOR pathway-ultimately mediating its anti-tumor effects.

Conclusion: This study indicated that aucubin inhibits the proliferation, invasion, and metastasis of liver cancer by upregulating the HMGB1/RAGE axis and targeting the PI3K/AKT/mTOR signaling pathway. The results of this study highlighted the potential of aucubin as a therapeutic agent for suppressing liver cancer.

Introduction: Immune regulatory genes, such as PLXNB2, play critical roles in the tumor microenvironment, yet their specific functions in Multiple Myeloma [MM] remain largely unclear.

Methods: Transcriptomic and clinical data for MM were retrieved from the Gene Expression Omnibus (GEO) database and analyzed alongside immune regulation-related genes identified from previous Mendelian randomization analysis. Correlations between these genes and immune functions, clinical risk scores, and survival prognosis were evaluated. Virtual drug sensitivity screening was performed for MM immune-related prognostic risk genes. In vitro experiments, including cell cloning, Transwell assays, scratch tests, and ELISA, were conducted to validate findings.

Results: PLXNB2 expression was positively correlated with improved MM prognosis, whereas LMNB1 expression showed a negative correlation. MM cell lines exhibited reduced PLXNB2 and increased LMNB1 expression. Overexpression of PLXNB2 and knockdown of LMNB1 significantly inhibited MM cell proliferation, invasion, and migration. Furthermore, these manipulations decreased PD1 and CTLA-4 expression, enhancing the cytotoxic activity of immune cells against MM cells.

Discussion: Our findings highlight the potential immune regulatory functions of PLXNB2 and LMNB1 in MM progression. The interplay between these genes may influence immune evasion and tumor aggressiveness, providing insights into potential therapeutic targets.

Conclusion: Reduced PLXNB2 expression may drive LMNB1 upregulation, suppress immune cell responses, and promote MM progression. These genes represent promising biomarkers and therapeutic targets for improving MM treatment strategies.

Introduction: Leukemia and radiation-induced liver toxicity are significant health challenges requiring effective therapeutic strategies. This study aimed to evaluate the therapeutic efficacy and radiosensitizing effects of Diosgenin-loaded silver nanoparticles (Dio-AgNPs) in ENU-induced leukemic mice, with a focus on their dual role in mitigating leukemia progression and γ-irradiation-induced hepatotoxicity.

Methods: Dio-AgNPs were synthesized and characterized using TEM, UV-Vis spectroscopy, FT-IR spectroscopy, and encapsulation efficiency analysis. Leukemic mice were treated with Dio-AgNPs (90 mg/kg b.w.) and γ-irradiation (2 Gy). Biological assays assessed hematological parameters, liver function, oxidative stress biomarkers, and gene expression (Nrf2, ABCC1, NQO1). Molecular docking analyzed diosgenin's binding affinities to target proteins. Histological evaluation of liver tissues and in silico ADMET profiling were also performed.

Results: Dio-AgNPs exhibited a mean diameter of 51.60 ± 1.54 nm, zeta potential of -19.5 ± 0.2 mV, and high encapsulation efficiency (84.98 ± 0.45%). Treatment significantly improved blood parameters (e.g., 39.4% increase in Hb, 41.5% reduction in WBCs), reduced liver enzymes (40.4% decrease in AST), and lowered oxidative stress (50.1% reduction in MDA). Synergy with γ-irradiation enhanced radiosensitivity (IC50: 24.55 μg/mL vs. 58.35 μg/mL alone). Molecular docking revealed strong binding to Nrf2 (-9.04 kcal/mol), ABCC1 (-10.05 kcal/mol), and NQO1 (-10.71 kcal/mol). Histology confirmed hepatoprotection, with minimal degeneration in combination-treated groups.

Discussion: Dio-AgNPs demonstrated multifaceted benefits, including anti-leukemic, antioxidant, and anti-inflammatory effects, amplified by γ-irradiation. The activation of the Nrf2 pathway and modulation of detoxification genes (ABCC1, NQO1) underpinned their therapeutic mechanism. Limitations include a single timepoint analysis and the need for human-relevant validation.

Conclusion: Dio-AgNPs are a promising dual-function therapy for leukemia and radiationinduced liver damage, combining targeted cytotoxicity with organ protection. Future research should optimize dosing and explore clinical translation.

Artemisinin, a natural compound derived from Artemisia annua, has significantly impacted the treatment of malaria and has shown promise in various other therapeutic applications. This review explores the molecular structure of artemisinin and its derivatives, as well as advancements in synthetic and semi-synthetic production methods, and their broader therapeutic effects beyond malaria, including potential uses in cancer, neurological disorders, and viral infections. It also discusses contemporary drug delivery innovations, such as nanoparticles and liposomal systems, which aim to enhance the bioavailability and targeted action of artemisinin, while addressing issues of drug resistance, particularly in parasitic diseases like malaria. The future of artemisinin research is expected to focus on the development of novel derivatives and innovative formulations that leverage nanomedicine, with significant implications for global health and improved therapeutic efficacy.

Introduction: Traditional cancer therapies like chemotherapy and radiotherapy frequently face challenges, such as systemic toxicity, the development of resistance, and poor tolerance among patients. Recently, there has been a growing interest in herbal bioactive compounds because of their wide-ranging anticancer properties and natural sources. Nonetheless, the clinical use of these compounds is restricted by their low solubility in water, limited bioavailability, and rapid metabolic clearance.

Methods: This review comprehensively assesses studies from 2010 to 2023 that investigate nanoformulation strategies aimed at enhancing the delivery of herbal bioactive agents in cancer treatment. The selection of studies was based on their examination of important nanocarrier systems, such as polymeric nanoparticles, liposomes, and lipid-based delivery platforms. The focus was on advancements in pharmacokinetics, drug targeting, and therapeutic outcomes.

Results: Research shows that nanoformulated herbal compounds show improved stability, solubility, and controlled release characteristics. Polymeric and lipid-based nanocarriers significantly enhance drug accumulation in tumor tissues, thereby improving antitumor effectiveness and reducing systemic side effects. Numerous studies also demonstrate increased cellular uptake and extended circulation times with nano-encapsulated phytochemicals.

Discussion: Nanoformulation technologies have effectively tackled numerous pharmacological challenges linked to herbal therapeutics. However, while laboratory and preclinical outcomes are promising, obstacles like obtaining regulatory approval, scaling up production, and ensuring consistent quality control impede clinical application. Additionally, the variability in plantderived compounds requires standardization to ensure reproducibility and safety.

Conclusion: Nanoformulations of herbal bioactive compounds mark a significant advance in cancer treatment, providing enhanced solubility, targeted delivery, and lower toxicity. Despite the progress made, additional research is required to refine these formulations, address manufacturing and regulatory challenges, and incorporate these strategies into personalized cancer therapy models.

Drug resistance (MDR) poses a significant challenge in breast cancer (BrCa) treatment, resulting in reduced efficacy and increased tumor recurrence. Resolving MDR in BrCa is necessary for improving the clinical efficacy of antitumor therapy. However, the molecular mechanisms underlying MDR are complex and involve various biological processes, including ABC drug transporter-mediated drug efflux, abnormal drug metabolism, and the development of the tumor microenvironment. The abnormal expression of ABC transporter proteins constitutes a critical mechanism driving MDR in BrCa. Factors like breast cancer stem cells (BCSCs), epigenetic changes, cell membrane lipids, and microenvironmental components affect the expression and function of ABC transporter proteins in BrCa. Here, we focus on the roles of Pglycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP) in relation to MDR. Additionally, we review the factors affecting the expression and function of these transporters, emphasizing strategies such as gene modification, drug development, and modulation of cell membrane lipids.

Introduction: Ependymoma is the third most common brain tumor in children, with a high recurrence rate and poor prognosis. The traditional treatment of ependymoma is surgery and radiation therapy. However, the effectiveness of conventional chemotherapy has been modest. Recent breakthroughs in molecular biology and genetics have opened doors to more targeted and effective therapeutic approaches. Complex mutations, such as CDK4 amplification in anaplastic ependymoma, are infrequently documented, warranting further investigation.

Case presentations: This case study presents a twelve-year-old girl with a WHO Grade III anaplastic ependymoma. She underwent two surgical procedures, followed by radiotherapy and chemotherapy. Despite this comprehensive treatment, she experienced a relapse after one year. Genetic testing identified CDK4 amplification in the tumor tissue. Subsequently, based on the genetic finding, she was treated with a CDK4/6 inhibitor, Dalpiciclib, in combination with bevacizumab. So far, she has survived for over 48 months following her surgery and continues to be monitored, underscoring the remarkable efficacy of the treatment.

Conclusions: This report represents the first use of the CDK4/6 inhibitor Dalpiciclib for the treatment of anaplastic ependymoma. The treatment was guided by insights from next-generation sequencing (NGS) analysis and has shown promising results in terms of patient survival.

Introduction: The CUGBP ELAV-like family member 2 (CELF2) gene is irregularly expressed in various types of cancer. However, the role of CELF2 in stomach adenocarcinoma (STAD) remains unclear. This study aims to elucidate its potential role in modulating tumor behavior in STAD, as well as its correlation with tumor-infiltrating immune cells.

Methods: Bioinformatics analysis methods were employed to investigate the CELF2 expression levels of CELF2 in STAD and its correlation with clinicopathological factors. CELF2 expression was quantified in STAD cells using qRT-PCR and Western blot. Immunohistochemistry confirmed CELF2 expression in STAD versus adjacent normal tissues. The effects of CELF2 expression on cell proliferation were evaluated using CCK-8 and colony formation assays, and migration and invasion assays evaluate cellular motility and invasiveness. Differential expression and protein-protein interaction (PPI) network analysis were conducted to predict the downstream targets of CELF2.

Results: Our findings revealed that CELF2 expression was significantly reduced in STAD tissues and was correlated with patient survival outcomes. Moreover, CELF2 overexpression demonstrated a notable inhibitory effect on cell proliferation, migration, and invasion in STAD cells. Importantly, CELF2 appeared to exert its effects through the regulation of the downstream target gene adiponectin (ADIPOQ). The knockdown of ADIPOQ effectively negated the inhibitory effects of CELF2 on cell proliferation and migration.

Discussion: This study underscores CELF2 as a tumor suppressor in STAD, whose downregulation promotes progression and correlates with poor prognosis. The CELF2/ADIPOQ axis represents a new regulatory pathway with therapeutic implications. The lack of deeper mechanistic insights into how CELF2 regulates ADIPOQ also warrants further investigation.

Conclusion: CELF2 acts as a tumor suppressor in STAD by inhibiting proliferation, migration, and invasion, partly through regulating ADIPOQ and influencing the immune microenvironment. It represents a promising prognostic biomarker and new therapeutic target, with the CELF2/ADIPOQ axis offering a specific pathway for future drug development.

The transcriptional enhanced associate domain (TEAD) family of transcription factors and their coactivators play pivotal roles in the Hippo-YAP/TAZ pathway, a critical regulatory axis involved in oncogenesis and tumor progression. To investigate the functional interactions of TEAD transcription factors, we performed comprehensive analyses of gene regulatory networks associated with TEADs. TEADs regulate oncogenesis and tumor progression through interactions with upstream oncogenic signaling pathways and the regulation of downstream target genes. As pivotal transcription factors, TEADs critically regulate multiple oncogenic processes, including epithelial-mesenchymal transition (EMT), proliferation, apoptosis, migration, invasion, metastasis, and aerobic glycolysis in cancer cells. TEADs are regulated by numerous non-coding RNAs [ncRNAs] through the Hippo, AKT, and TGF-β signaling pathways in cancers. These insights establish a strong molecular rationale for developing TEAD-targeted therapeutic strategies in cancer treatment.

Introduction: This study aims to explore the potential of LMNB1 and LMNB2 as prognostic risk factors in hepatocellular carcinoma (HCC) and investigate small-molecule drugs targeting both for therapeutic application.

Methods: LMNB1 and LMNB2 expression in HCC was assessed using TCGA data and validated in clinical specimens. Kaplan-Meier and Cox models evaluated prognostic relevance. Drug sensitivity screening using CTRP and GDSC databases highlighted GSK461364 (a selective PLK1 inhibitor), whose effects were validated in Hep3B and SK-HEP-1.

Results: LMNB1 and LMNB2 were aberrantly up-regulated in HCC tissues and contributed to the poor prognosis of HCC patients. Co-expression modules and enriched pathways of LMNB1 and LMNB2 were linked to nuclear architecture and cell senescence, indicating their roles in genomic stability and cell cycle progression. GSK461364 was validated to inhibit the cell viability of HCC cells. It suppressed the expression of LMNB1 and LMNB2 but not PLK1, suggesting its anti-HCC effect depends on inhibition of LMNB1/2 rather than PLK1.

Discussion: Our findings suggest that LMNB1 and LMNB2 could serve as prognostic biomarkers. GSK461364 likely exerts anti-HCC effects through suppression of LMNB1 and LMNB2 expression. Further in vivo validation and molecular mechanism studies are needed to establish its clinical utility.

Conclusion: LMNB1 and LMNB2 are prognostic factors for HCC. GSK461364 is a novel therapeutic candidate for HCC, with anti-HCC effects associated with LMNB1/2 suppression.