Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis and resistance to temozolomide (TMZ). The role of downregulated circular RNAs (circRNAs) in GBM progression remains unclear.

Breast cancer remains one of the most prevalent and deadly cancers worldwide, affecting women. This review explores the potential of lipid-polymer hybrid nanoparticles (LPHNPs) as a next-generation drug delivery system for breast cancer therapy. The review categorizes LPHNPs and discusses their unique structure, preparation methods, and applications in cancer therapy. It delves into the various methods of preparing for LPHNPs. Furthermore, it examines the application of LPHNPs in treating various cancers, focusing on breast cancer, where they have shown promise in delivering single drugs, drug combinations, and nucleic acids like siRNA and miRNA. The ability of LPHNPs to overcome drug resistance and enhance therapeutic efficacy is emphasized, along with their potential for personalized medicine. The literature search was performed using PubMed, Scopus, and Web of Science databases to identify relevant studies published from 2009 to 2025. The review summarizes recent patents related to breast cancer treatment, showcasing advancements in drug delivery systems and therapeutic approaches. The conclusion underscores the transformative potential of LPHNPs in revolutionizing breast cancer treatment, provided that challenges in formulation, scalability, and long-term safety are addressed. Continued research and collaboration between researchers, clinicians, and regulatory bodies are essential to realize the benefits of LPHNPs in personalized cancer therapy. [Figure: see text].

Achieving better clinical outcomes in cancer research requires a deeper understanding of tumoral biology and the application of this knowledge within a clinic setting. The aim of this review is to briefly summarize the current knowledge on H3R molecular pharmacology, the clinical use of H3R antagonists, and the most recent findings reporting H3R role in cancer biology. We will discuss in detail the current landscape and clinical perspectives of the modulation of this H3R on cancer progression and treatment. We propose H3R as a promising molecular target for cancer drug repurposing and development.

Triple-negative breast cancer (TNBC) is a particularly aggressive and frequently recurring form of breast cancer, where chemotherapy is the primary treatment approach. Unfortunately, the development of resistance to chemotherapy poses a considerable challenge, restricting the already limited therapeutic alternatives for recurrent cases. Here, we generated two Taxol-resistant TNBC cell lines with a dose-escalation method to mimic chemotherapy resistance in vitro. These cells exhibited reduced growth rates, altered morphology and evasion of apoptosis. Transcriptome analysis uncovered elevated ABCB1 expression and multidrug-resistant phenotype in these resistant cells. To comprehensively investigate the key epigenetic regulators of Taxol resistance, we conducted chromatin-focused genetic and chemical screens and pinpointed Bromodomain and PHD Finger Containing 1 (BRPF1) as a novel regulator of Taxol resistance. Knockout of BRPF1, the reader protein in the MOZ-MORF histone acetyltransferase complex, but not the other complex members, sensitized resistant cells to Taxol. In addition, BRPF1 inhibitors, PFI-4 and OF-1, in combination with Taxol significantly reduced cell viability. Transcriptome analysis upon BRPF1 loss or inhibition revealed a negative impact on ribosome biogenesis-related gene sets, resulting in a global decrease in protein translation in Taxol-resistant cells. CUT&RUN-qPCR analysis demonstrated that BRPF1 directly binds to the ABCB1 promoter, enhancing its expression toward inducing a multidrug-resistant phenotype. Conversely, knockout or inhibition of BRPF1 leads to decreased ABCB1 expression. Our findings uncover a comprehensive molecular framework, highlighting the pivotal role of epigenetic reader protein BRPF1 in Taxol resistance and providing potential avenues for therapeutic intervention in TNBC.

Shikonin, a natural bioactive compound derived from medicinal plants, demonstrates extensive pharmacological properties in traditional Chinese medicine, and exhibits significant therapeutic potential for modern diseases such as cancers and immune-related disorders. Over the past decades, research has focused on its anticancer, anti-inflammatory, and immunomodulatory activities. In vitro and in vivo studies have elucidated its mechanisms at cellular and molecular levels. Shikonin exerts antitumor effects by inducing multiple cell death modalities through caspase-3 activation, ROS generation, modulation of ATF3 expression, modulation of RIP1/RIP3 signaling, and activation of the BAX/caspase-3/GSDME pyroptosis axis. Furthermore, it suppresses tumor cell proliferation, inhibits metastasis, and blocks cell cycle progression by downregulating oncogenic c-Myc and MMP2 while upregulating the cell cycle inhibitor P21. It also enhances chemosensitivity via β-catenin modulation. Furthermore, shikonin inhibits PD-L1 expression through the NF-κB/STAT3 and NF-κB/CSN5 pathways, and mediates tumor immunomodulation as a result. Its anti-inflammatory capacity is attributed to the regulation of immune cells, signaling pathways (e.g., TLR4/MyD88/NF-κB), and pro-inflammatory cytokines (e.g., TNF-α, IL-6). The regulation of these processes thereby enhances anti-inflammatory responses in target organs and mitigates autoimmune diseases. This review systematically deciphers shikonin's mechanisms in tumor suppression, inflammation resolution, and immune regulation, offering novel insights for interdisciplinary research bridging oncology, immunology, and inflammation biology, and laying a foundation for advancing immune-modulating cancer therapies and autoimmune disease management.

This paper comprehensively examines the anticancer mechanisms and therapeutic potential of β-sitosterol, a naturally occurring phytosterol found in various plants. β-Sitosterol has shown significant efficacy in inhibiting tumor growth and metastasis through various biological pathways, including inducing apoptosis, arresting cell cycle progression, and suppressing cell proliferation, invasion, and migration. We highlight the key mechanisms by which β-sitosterol exerts its effects, such as modulating apoptosis-related signaling pathways like those of the Bcl-2 family proteins and reactive oxygen species production. Furthermore, β-sitosterol's role in disrupting the epithelial-mesenchymal transition and its impact on tumor metabolism, particularly in cholesterol and glucose regulation, are discussed. The article also explores the potential of β-sitosterol to enhance chemotherapy sensitivity, making it a promising adjunct in cancer treatment. Additionally, we incorporate a bibliometric analysis and network pharmacology approach to identify potential therapeutic targets and pathways influenced by β-sitosterol, providing new insights into its multifaceted anticancer activities. These findings underscore the potential of β-sitosterol as a novel anticancer agent, warranting further research and clinical investigation to optimize its future therapeutic application.

Valeriana jatamansi Jones (V. jatamansi) has a long history of medicinal use owing to its significant therapeutic effects, particularly in the treatment of mental diseases such as depression, and on account of its cytotoxicity against various cancer cells. The chemical composition, pharmacological properties, and mechanisms of V. jatamansi have been extensively explored in various studies published between 2017 and 2023 on major databases such as Web of Science, PubMed, and CNKI[Formula: see text] Investigations have identified 128 compounds including iridoids, sesquiterpenoids, volatile oils, lignans, and miscellaneous compounds based on their structural characteristics. Pharmacological research has documented its impact on the central nervous system, and its antitumor, gastroprotective, antioxidant, and anti-inflammatory effects. In particular, iridoids stand out among these compounds, and iridoid-enriched fraction from V. jatamansi (IEFV), identified by several pharmacological experiments, exhibits notable protective properties against diseases of the central nervous system and several cancers. In summary, V. jatamansi holds potential as an adjunct in cancer treatment, enhancing its therapeutic efficacy.

Lung cancer is a serious threat to human health and has become a major challenge to global public health. Evodiamine, a naturally indole alkaloid extracted from Tetradium ruticarpum (A. Juss.) T.G. Hartley, has been found to have toxic effects on various tumor cells. Nevertheless, the mechanism by which evodiamine on lung cancer remains unknown. In this study, the effects and possible mechanisms of evodiamine on lung cancer were investigated. Our data demonstrated that evodiamine suppressed the proliferation and migration of A549 and H1299 cells. Mechanistically, evodiamine operated by downregulating the phosphorylated expression of focal adhesion kinase (FAK), signal transducer and activator of transcription 3 (STAT3), and protein kinase B (AKT), while concurrently reducing the expression of CyclinA2 and CyclinB1. Notably, evodiamine inhibited the proliferation of A549 and H1299 cells by blocking the phosphorylation of FAK/STAT3/AKT induced by epidermal growth factor (EGF). Furthermore, the subcutaneous tumor models found that evodiamine slowed the growth of lung cancer in vivo. Collectively, our results showed that evodiamine inhibited the cell proliferation and migration of NSCLC and slowed subcutaneous tumor growth probably by the EGF-mediated FAK/STAT3/AKT pathway. These findings suggested that evodiamine is a promising therapeutic candidate worthy of further exploration for NSCLC treatment.

In this study, sixteen novel 1,2,3-triazole-substituted salicylic acid phenolic-hydrazone hybrids were synthesized and characterized using NMR, IR, HRMS, and HPLC techniques. The compounds were evaluated for their anticancer potential against HCT-116, Caco-2 and HT-29 colorectal carcinoma cells and normal BEAS-2B epithelial cells. Among them, compound 10k exhibited potent antiproliferative effects on HCT-116, Caco-2 and HT-29 with IC50 values of 6.84, 10.21, and 9.47 μM, respectively, which were significantly lower than the reference drug sorafenib (IC50 = 18.25, 13.80 and 7.89 μM) for HTC-116 and Caco-2. Biological assays demonstrated that 10k effectively downregulated TGF-β2 receptor and cytokine expression in a dose-dependent manner, indicating its role in modulating the TGF-β signaling pathway. Apoptosis analysis suggested that cytotoxicity was mediated via non-apoptotic mechanisms. Molecular docking studies revealed a strong binding affinity for compound 10k with a docking score of -11.28 kcal/mol. Furthermore, 250 ns molecular dynamics simulations confirmed the stability of the ligand-receptor complex with an RMSD value stabilized around 1.15 Å. Key interactions included hydrogen bonds with Asn-332, π-π stacking, and halogen bonding. ADMET predictions confirmed favorable drug-like properties with good permeability and safety profiles. These findings position compound 10k as a promising lead candidate for colorectal cancer therapy, targeting TGF-β2 mediated pathways with high efficacy and selectivity.

Targeted inhibition of tubulin polymerization or histone lysine-specific demethylase 1 (LSD1) is considered as a promising therapeutic strategy for cancer treatment. In this work, we reported the discovery of novel 1,2,3-triazole arylamide derivatives bearing dithiocarbamate moiety as dual tubulin polymerization and LSD1 inhibitors through the pharmacophore hybridization strategy, which were derived from the natural product Erianin, and evaluated their anticancer activity through in vitro assays. Among them, compound L-6 was identified as a potent dual tubulin polymerization and LSD1 inhibitor with effective anticancer potency, which demonstrated broad-spectrum antiproliferative activity in vitro with IC50 values below 100 nM against 13 cancer cell lines. Notably, it displayed remarkable inhibitory potency on MGC-803 (IC50 = 33 nM) and HGC-27 (IC50 = 49 nM) gastric cancer cells, which surpassed those of Erianin and the LSD1 inhibitor ORY-1001. Mechanism explorations demonstrated that compound L-6 inhibited tubulin polymerization by targeting the colchicine binding site, thereby disrupting the microtubule network in gastric cancer cells. Additionally, it increased the methylation levels of H3K4me1/2 and H3K9me2/3 in a concentration-dependent manner, thus achieving epigenetic regulation. This dual mechanism involving microtubule depolymerization and epigenetic modulation enabled compound L-6 to effectively suppress colony formation, induce G2/M phase arrest, and promote apoptosis in gastric cancer cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. These findings suggested that compound L-6, as a novel dual-target inhibitor of tubulin and LSD1, exhibited potential for the treatment of gastric cancer.

Cancer remains a critical global health challenge, with conventional treatments such as chemotherapy, radiation, and immunotherapy often hindered by issues like poor selectivity, systemic toxicity, and drug resistance. Recent advancements in materials science, particularly in the field of nanotechnology and drug delivery systems, have opened new avenues for more effective cancer therapies. This review focuses on copper-doped polymer thin films-an emerging class of therapeutic materials with promising anti-cancer properties. Copper, a biologically essential trace element, contributes to cancer cell apoptosis by inducing oxidative stress and has also been shown to enhance the efficacy of chemotherapeutic agents, helping to overcome drug resistance in various cancers. The paper reviews a broad spectrum of recent literature, encompassing both experimental and theoretical studies related to the synthesis, structural characterization, and biomedical performance of these materials. Methodologies such as in vitro cytotoxicity assays, in vivo treatment models, and physicochemical analyses are discussed to provide a comprehensive understanding of their therapeutic potential. The review concludes by highlighting the advantages, challenges, and future prospects of integrating copper-doped polymer thin films into advanced cancer treatment strategies.

Breast cancer is the most common malignancy in women, with approximately 20-30% of all diagnosed cases characterized by HER2 overexpression. Several HER2-targeted cytotoxic conjugates have been developed, but their efficacy is limited. One of the main obstacles restraining the effectiveness of HER2-specific cytotoxic conjugates is their low internalization, as HER2 is immobile mainly on the cell surface. Therefore, there is a need to develop novel HER2-selective cytotoxic conjugates that will overcome HER2 immovability and, by this, ensure efficient drug delivery into HER2-overexpressing cancer cells. Here, we present a novel system for generating high affinity, self-assembling, inherently fluorescent, and multivalent HER2 ligands. The developed HER2-specific ligands largely overcome the innate stability of HER2 in the plasma membrane by triggering clathrin-independent aggregation-dependent endocytosis of the receptor. To exploit the pro-endocytic potential of developed proteins, we constructed the tetravalent fluorescent cytotoxic conjugate TetraFHER2-vcMMAE and demonstrated its high potency and selectivity against HER2+ breast cancer cells.

GBM is an aggressive primary malignant brain tumor that has a poor prognosis. Molecular characterization of GBM has shown that EGFR mutations are present in over 50% of tumors. However, EGFR inhibitors have not shown clinical efficacy in contrast to other EGFR-driven neoplasms due to the unique EGFR biology found in GBM. Upfront combinatorial therapy featuring EGFR tyrosine kinase inhibitors (TKI) may overcome these challenges. To identify combinatorial drug targets within the kinome, we temporally characterized drug-induced kinome rewiring in isogenic, genetically engineered Cdkn2a-deleted mouse astrocytes expressing human EGFRvIII. We utilize RNA sequencing and multiplex inhibitor beads, coupled with mass spectrometry, to demonstrate that kinome rewiring exhibits both shared and unique kinases after acquired resistance develops to EGFR TKI, despite using models with a common genetic background. Additionally, we noted that kinases altered in the acute setting are distinct from those in acquired resistance. By identifying kinome vulnerabilities throughout the acute, dynamic drug response process, we generated a kinase signature associated with EGFR inhibition. Further molecular interrogation of signature genes revealed that drug treatment induces an unexpected increase in Cdk6 protein, but not mRNA, despite live cell imaging and transcriptomic evidence indicating decreased proliferation. Survival experiments with orthotopic allografts show that upfront combination inhibition of Cdk6, using abemaciclib, and EGFR, using neratinib, significantly prolonged median survival compared to neratinib alone. Our findings suggest that identifying and inhibiting targets with synthetic lethality in the upfront combinatorial setting is a viable approach for precision oncology and may help provide an avenue to overcome the resistance mechanisms that contributed to the failures of EGFR as a molecular target in GBM.

Immune-related adverse events (irAEs) are recognized in oncology, particularly with immune checkpoint inhibitors and other targeted therapies. Brentuximab Vedotin (BV), is an anti-CD30 antibody-drug conjugate- its association with immune-mediated myositis remains unexplored. We report a case of an adolescent with Hodgkin lymphoma (HL) who developed neuropathy and myositis following BV therapy.

This research employed Ananas comosus (pineapple) peel waste (PPW) extract for producing selenium nanoparticles (SeNPs) using an ecologically feasible way, aimed at various medical uses. Our analysis demonstrated that the PPWextract was a significant supplier of several important phytochemicals. The synthesized SeNPs were comprehensively characterized via XRD, FTIR, SEM, EDX, UV-Vis, and HRTEM which exhibiting a spherical shape with dimensions between 33 and 73 nm. Additional experimental assessments of SeNPs were carried out to ascertain their suitability for usage in biology applications. The findings suggest that obtained SeNPs may effectively combat multiple bacteria, including S. aureus, E. coli, B. subtilis, E. faecalis, and K. pneumonia. Additionally, SeNPs exhibited antibiofilm capacity for both MRSA and E. coli with inhibition reported to be 64.8% and 54.4% at 100 µg/mL respectively. In the range of 62.5-31.25 µg/mL SeNPs reduced expression of two essential genes required for S. aureus to generate biofilms, cna (0.9 fold change), and quorum sensing gene LuxS of E. coli (4.2 folds of control to 3.4 folds of treated) in comparison to the RecA gene. The antioxidant capacity of SeNPs reported an IC50 value of 98.3 µg/mL. The formed SeNPs demonstrated anticancer efficacy in combating the HepG2 malignant cell line, with an IC50 value of 113.02 µg/mL.

Targeting cancer metabolism has emerged as an attractive therapeutic strategy in recent years, despite the "Warburg effect" phenomenon is discovered about a century ago. Based on this phenomenon, cancer cells rely on aerobic glycolysis and require higher rate of glucose consumption compared to normal cells and the hexokinase-2 (HK-2) enzyme catalyzes the first step of glucose metabolism. Consistent with the notion, HK-2 expression is highly elevated in most malignancies and that predicts poor survival in patients. Thus, inhibiting the HK-2 activity may be a potential metabolic target for cancer therapy. Lonidamine (LND) is known as a potential anti-cancer drug through HK-2 inhibition with varying degrees of efficacy in different malignancies. LND shows potency through voltage-dependent anion channel (VDAC) and HK-2 interaction on mitochondrial membrane. Therefore, we designed and synthesized novel LND analogs to improve its molecular and functional properties. We first performed chemical and structural characterization of these LND analogs and tested their biological activity by in vitro assays and in vivo in mouse xenografts. Among these potent HK-2 inhibitors, Compound 20 was identified as a promising lead compound with anti-tumor activity. Based on the three different cancer cell lines we investigated, our novel LND analogs proved to be more potent than the original molecule. Our findings provide convincing evidence for potentially designing novel analogs of LND and beyond to further improve biological and functional properties existing drugs. Further proven in preclinical settings, our approach may lead to development of more effective therapeutics benefiting patients.

Langdu is generally considered as the roots of Euphorbia fischeriana, Euphorbia ebracteolata and Stellera chamaejasme. However, whether these three plants can substitute for one another has always been a concern. This article aims to clarify the differences among the three Langdu species in chemical constituents and anti-tumor effects. This study provides a qualitative and quantitative analysis of eight diterpenoids and one flavonoid in Langdu samples and IC50 curves for these compounds, which can serve as a basis for identification and usage.

Bone tumors are rare and diverse neoplasms with local and systemic impacts. Current therapies like surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy have had mixed success; significant hurdles persist. Surgery may cause a series of complications and has limited applicability. Systemic chemotherapy notably has a narrow therapeutic window. Besides, the bone microenvironment is extremely complex. These aspects fuel tumor growth and hinder drug delivery. Innovations in drug delivery systems enable spatiotemporal drug control, enhancing tumor accumulation while minimizing systemic toxicity. Examples include bone-targeted nanoparticles (e.g., bisphosphonate-modified carriers), stimuli-responsive systems (pH/redox-sensitive release), and hybrid platforms (e.g., nanocarriers co-loading chemotherapeutics and immunomodulators). These strategies address tumor heterogeneity and microenvironmental barriers, demonstrating improved efficacy in preclinical models. In this review, we comprehensively summarize the most recent advancements in drug delivery systems designed for bone tumor therapy. The key approaches discussed are as follows: drug combination strategies, metal-organic frameworks and inorganic nanomaterials, specificity of bone tissue, bone-targeting strategies, organic combination of response strategies, nanocarrier-based delivery systems, and emerging technologies. Despite progress, challenges like scalability, biocompatibility, and regulatory hurdles limit clinical translation. Future directions include integrating AI for optimized drug delivery system design, developing personalized/patient-specific delivery methods, and exploring combinatorial approaches. This review synthesizes cutting-edge DDS technologies and addresses translational challenges, providing actionable insights to bridge laboratory discoveries and clinical applications.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma characterized by a myxoid matrix and a distinctive lobulated architecture, composed of cords and clusters of uniform round-to-rhabdoid cells. At the molecular level, EMC is defined by specific gene fusions involving NR4A3, most frequently EWSR1::NR4A3. The responses to conventional chemotherapy are limited, and the prognosis for patients with advanced or metastatic disease remains poor. We successfully developed the NCC-EMC1-C1 cell line using surgically resected tumor tissue from a patient with EMC. NCC-EMC1-C1 cells exhibited constant proliferation in monolayer culture, spheroid formation in low-attachment plates, and migration. High-throughput screening of 221 anticancer drugs using NCC-EMC1-C1 identified three candidates, brigatinib, panobinostat, and romidepsin, that demonstrated low IC50 values. These data indicated the utility of NCC-EMC1-C1 for the experiments based on screening. We conclude that NCC-EMC1-C1 is a valuable tool for preclinical and basic research on EMC.

Owing to its less oxygen-dependent mechanism, type I photodynamic therapy (PDT) has exhibited significant superiority over the more common type II PDT in the treatment of hypoxic tumors. Supramolecular coordination complexes (SCCs) have shown great potential in photodynamic cancer therapy; however, SCC-based photosensitizers which can achieve type I PDT have rarely been reported. Herein, we present the design and synthesis of a novel heteroleptic/trimetallic OsII-RuII-ZnII Sierpiński triangle ST-2 via coordination-driven self-assembly. The distinctive SCC ST-2 displayed high generation ability of reactive oxygen species (ROS) and boosted the production of O2-• involved in the type I mechanism. Detailed in vitro investigations demonstrated ST-2 exhibited excellent PDT efficacy against all tested cancer cell lines with low IC50 values in the subnanomolar range and high phototoxicity indexes (PI) up to 750 even under hypoxic conditions and induced cancer cell death mainly through type I PDT. The anticancer mechanism could be ascribed to the mitochondrial and lysosomal damages as well as cell apoptosis and cell cycle arrest. Further studies confirmed that ST-2 disintegrated 3D multicellular tumor spheroids and effectively inhibited the growth of solid hypoxic tumors in mice with minimal side effects. This work not only provides an alternative strategy for the development of highly efficient type I photosensitizers but also opens new possibilities for Sierpiński triangles in biomedicine.