Exploration of targeted anti-tumor therapy最新文献

Immune checkpoint inhibitors (ICIs) are established treatments for various malignancies, including lung, kidney, and colorectal cancers. However, their broad use has led to an increase in immune-related adverse events (irAEs), with thyroiditis, colitis, and pneumonitis being the most common. Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe irAE characterized by excessive immune activation, leading to systemic inflammation and multi-organ dysfunction. We present three cases of ICI-induced HLH in patients with lung cancer who were treated with ICIs. All patients showed elevated inflammatory markers and responded to high-dose corticosteroids without the addition of etoposide. These cases underscore the importance of early recognition and treatment of HLH in patients receiving ICIs to mitigate morbidity and mortality. Large-scale studies are needed to establish standardized guidelines for diagnosing and managing ICI-induced HLH.

Cancer is one of the leading global causes of mortality and morbidity, so it needs early diagnosis and therapies. Traditional diagnostic and therapeutic strategies are inadequate due to several limitations, such as poor specificity, systemic toxicity, and delays, while metal-grafted Gr nanostructures have emerged as promising theranostic platforms due to their unique electronic, optical, and structural properties. Metals such as Fe₃O₄, Au, Ag, TiO₂, Pd, Pt, Bi, ZnO, and Cu grafted onto the Gr surface impart electronic modulation, enhance surface area, flexibility, conductivity, reactivity, biomolecular interactions, and biosensing, thereby enabling precise biomarker detection, targeted drug delivery, imaging, and photothermal/photodynamic therapy (PTT/PDT). Eco-friendly synthesis using plant extracts and microbes offers a sustainable and biocompatible alternative to conventional chemical synthesis. However, challenges remain, such as homogenous doping, synthetic complexity, long-term safety, and clinical scalability. Innovations such as scalable, cost-effective, biocompatible nanofibers, nanopapers, microfluidic, and wearable biosensors are being explored by incorporating AI and advanced diagnostic tools for advanced biomedical devices. In vitro, half maximum inhibitory concentrations (IC₅₀) studies show that size- and dose-dependent nanohybrids such as Fe₃O₄-Gr, γ-Fe₂O₃-Gr, Au-Gr, and Bi-Gr exhibited safer responses at lower concentrations 10-200 µg/mL across HBE, MCF-7, HeLa B, and LNCaP cell lines. Bi-Gr was tested on human liver cancer (HepG2) cell line, which exhibits higher reactivity despite a safer profile of Bi at ~53-88 µg/mL. Pd-Gr and Pt-Gr significantly reduced viability in prostate and ovarian cancer cells at 10-50 µg/mL, while ZnO-Gr, Ag-Gr, and Cu-Gr showed safer activity at lower concentrations on MCF-7. In vivo studies remain limited; median lethal dose (LD₅₀) values for Fe₃O₄-Gr and γ-Fe₂O₃-Gr were determined to be associated with rapid lethal biodistribution observed in the liver, lungs, and spleen. Metal-grafted Gr nanohybrids demonstrate immense potential for multifunctional cancer theranostics, though systematic in vivo toxicity studies still need to be explored by the intravenously administered route to lower the LD₅₀ of nanohybrids for their clinical translation.

Gynecological cancer remains one of the leading causes of mortality worldwide. Recent advances in genomic and molecular sequencing have significantly enhanced our understanding of the biological pathways that drive tumor progression and resistance to therapy. Targeted therapies, including monoclonal antibodies (mAbs), have revolutionized cancer treatment by selectively interfering with oncogenic proteins expressed on cancer cells. However, the long-term clinical benefit is often limited due to the emergence of drug resistance, frequently mediated by compensatory signaling pathways or immune escape mechanisms. To overcome these limitations, bispecific antibodies (bsAbs) represent an innovative class of therapeutic agents that have shown promising results across various medical fields. They have been developed to engage two distinct targets simultaneously, such as tumor antigens, immune effectors, or immunomodulatory checkpoints, thereby enhancing anti-tumor activity and reducing the risk of resistance. There are 17 bsAbs approved for clinical use in various countries, with numerous others currently in active development and over 600 bsAbs undergoing clinical trials worldwide. Among these, 11 have received FDA approval for the treatment of hematologic malignancies as well as solid tumors, including uveal melanoma, metastatic non-small cell lung cancer, small cell lung cancer, and biliary tract cancers. Although some studies have explored bsAbs in gynecological cancers, this area remains underdeveloped compared to other oncology fields. Most ongoing studies in this area are still in their early phases (phase I or phase II), and there is a need for optimization in terms of antibody design, efficacy, and safety profiles. Therefore, the purpose of this review is to present a comprehensive summary of the current research on bsAbs in gynecological cancers, with a focus on endometrial, cervical, and ovarian cancers. We will highlight ongoing clinical trials, discuss the mechanisms of action of these agents, and explore their potential benefits in enhancing treatment outcomes.

Aim: Hepatocellular carcinoma (HCC) displays both shared and ethnicity-specific molecular characteristics. Using transcriptomic data from The Cancer Genome Atlas (TCGA), we compared gene expression profiles between Asian and Caucasian HCC patients.

Methods: Gene expression profiles were analyzed using the PyDESeq2 implementation of DESeq2, applying size factor normalization and dispersion estimation. Differentially expressed genes (DEGs) were identified with thresholds of false discovery rate (FDR) of < 0.05 and |log₂FC| ≥ 1.0. Gene annotation, visualization, and pathway enrichment were conducted using Sanbomics, seaborn, and gene set enrichment analysis (GSEA) via the GSEApy package.

Results: A total of 387 and 250 genes were commonly upregulated and downregulated, respectively, in both populations, including the upregulations of GPC3 and PLVAP and the downregulations of FCN3 and OIT3, indicating their potential as universal HCC markers. Conversely, 16 genes were upregulated in Asians but downregulated in Caucasians, and 25 showed the reverse pattern. Asian-specific upregulation of AKR1B10, UBE2C, and S100P suggests links to viral etiology and immune modulation, while MDK, LCN2, and NQO1 were upregulated in Caucasians, implicating proliferative and metabolic roles. Functional enrichment analysis revealed distinct immune and metabolic pathways. Asians showed elevated ubiquitin ligase activity and suppressed inflammatory responses, while Caucasians exhibited enhanced cytokine signaling, complement activation, and xenobiotic metabolism.

Conclusions: These findings highlight key molecular differences in HCC across ethnicities and emphasize the value of TCGA data for identifying both shared targets and population-specific therapeutic strategies. Understanding these differences is crucial for advancing precision oncology and developing tailored interventions.

Aim: TNF-related apoptosis-inducing ligand (TRAIL) is a promising targeted anti-cancer agent for several types of cancer, including non-small cell lung cancer (NSCLC). The proteasome inhibitor bortezomib can further potentiate rhTRAIL-induced apoptosis in NSCLC cells. Here, the mechanisms underlying this sensitization were examined in TRAIL-sensitive H460 and TRAIL-resistant A549 and SW1573 NSCLC cells.

Methods: NSCLC cell lines were treated with rhTRAIL and bortezomib, and apoptosis was assessed through caspase activation assays, western blotting, and gene silencing of key apoptotic regulators, including Bid, XIAP, and cFLIP. Clonogenic assays were performed to evaluate long-term tumor growth suppression.

Results: Bortezomib sensitization mechanisms varied across NSCLC cell lines. Combined rhTRAIL/bortezomib treatment enhanced apoptosis across all cell lines. In TRAIL-sensitive H460 cells, rapid caspase activation was observed, with both extrinsic and intrinsic apoptotic pathways contributing to cell death. Sensitization in H460 cells was predominantly mediated via the caspase-8/Bid amplification loop. In A549 cells, the bortezomib sensitizing effect also relied on the caspase-8/Bid amplification loop. Additionally, the inhibition of Bid and XIAP emphasized the critical role of mitochondrial pathways in apoptosis. In SW1573 cells, limited caspase cleavage was detected, with distinct cleavage patterns suggesting cell-specific apoptotic mechanisms. In this cell line, bortezomib primarily enhanced the extrinsic apoptotic pathway, with XIAP depression further increasing apoptosis. Silencing cFLIP, a caspase-8 inhibitor, significantly improved rhTRAIL sensitivity, emphasizing the critical role of caspase-8 activation in overcoming resistance in SW1573. The clonogenic assay demonstrated that bortezomib combined with rhTRAIL significantly suppressed tumor growth, especially in resistant cell lines.

Conclusions: This study underscores bortezomib's ability to differentially enhance rhTRAIL-induced apoptosis by targeting multiple apoptotic regulators. The variety of effects that bortezomib can exert to enhance rhTRAIL-induced apoptosis makes it a very powerful combination for the treatment of NSCLC and various other types of cancer cells.

[This retracts the article DOI: 10.37349/etat.2025.1002332.].

The green synthesis of silver nanoparticles (AgNPs) has recently gained prominence as a sustainable and eco-friendly alternative to conventional physical and chemical methods. Utilizing biological entities such as plant extracts, bacteria, fungi, and biomolecules, the method acts by both reducing and stabilizing mechanisms. It does not use any harmful chemical substances, thus proving to be eco-friendly. Green-synthesized AgNPs exhibit enhanced biocompatibility, stability, and targeted delivery of the drug due to the use of naturally derived surface capping agents. These unique characteristics allow selective interference with cancer cells. The mechanism involved is the generation of reactive oxygen species (ROS), the induction of apoptosis, DNA damage, and cell cycle arrest. Green AgNPs also possess broad-spectrum antimicrobial, catalytic, antiparasitic, and anti-inflammatory properties, supporting the fact that they can be utilised in biomedical fields such as drug delivery, bioimaging, biosensing, tissue engineering, and regenerative medicine. Recent advancements have focused on controlling NP size, shape, and surface functionality to maximize efficacy while simultaneously minimizing cytotoxicity. This review provides a comprehensive analysis of the latest green synthesis strategies, their characterizations, and the molecular mechanisms by which they exert anticancer effects. Recent patents highlight the clinical potential of AgNPs in cancer therapy. US Patent 12201650 (2025) describes green synthesis using Caralluma sinaica, while other patents (WO2007001453, US7462753) outline adaptable biomedical formulations. Studies on biogenic AgNPs also show significant tumor inhibition and selective cytotoxicity against cancer cells. Furthermore, the article discusses current biomedical applications and critically evaluates the limitations, such as reproducibility, toxicity concerns, and scalability for clinical translation. Addressing these challenges is essential for the integration of green AgNPs into mainstream cancer therapeutics. The convergence of nanotechnology and biologically derived synthesis opens promising avenues for the development of safe, effective, and environmentally sustainable medical innovations.

Aim: The current study uses the depicted approach to synthesize curcumin-piperine loaded Poloxamer F-68 coated magnetic nanoparticles (CUR-PIP-F68-Fe₃O₄ NPs) to achieve a synergistic anti-cancer impact on an in vitro HCT-116 colon cancer cell. Integrating magnetic nanoparticle technology with phytoconstituents enhances the potential for targeted drug delivery with minimal systemic toxicity and facilitates therapeutic outcomes.

Methods: A Box-Behnken design was employed to optimize the CUR-PIP-F68-Fe₃O₄ NPs prepared by the co-precipitation method. Optimized formulation was evaluated for morphological characteristics, elemental composition, and magnetic properties. An in vitro cytotoxicity assay was conducted to observe the % viability of cells and to further calculate the IC50. Cellular uptake studies were investigated using confocal microscopy.

Results: Results showed that the optimised nanoparticles possessed a particle size of 158.7 ± 0.057 nm, zeta potential of -30.3 ± 0.1 mV, and encapsulation efficiency of 98.85 ± 0.066%. Analysis by vibrational sample magnetometer revealed that magnetic saturation was 75.6 emu/g and 50.7 emu/g for bare Fe₃O₄ nanoparticles and drug-loaded magnetic nanoparticles, respectively. Scanning electron microscopy (SEM) depicted the morphological characteristics; elemental composition of synthesized magnetic nanoparticles was confirmed by energy dispersive X-ray (EDX) analysis by illustrating the presence of C (13.50 ± 0.30%), Fe (78.81 ± 1.23%), and O (7.69 ± 0.29%). The MTT assay and cellular uptake studies unveiled that CUR-PIP-loaded magnetic nanoparticles possess a synergistic cytotoxic effect and the highest drug uptake against the HCT-116 colon cell line.

Conclusions: The combination approach of curcumin-piperine magnetic nanoparticles to HCT-116 cells enhanced the anticancer efficacy of the curcumin and further demonstrated the potential of this approach to conduct in vivo studies.

Lung cancer remains the leading cause of cancer mortality worldwide, with progress limited by tumor heterogeneity, drug resistance, and conventional therapy limitations. Nanotechnology-enabled drug delivery offers a transformative approach, enabling the precise engineering of nanocarriers for selective targeting, controlled release, and reduced toxicity. Recent innovations include inhalable systems that achieve localized pulmonary deposition, stimuli-responsive nanocarriers that release drugs in response to tumor microenvironment cues, and nano-immunotherapies that synergize with immune checkpoint blockade. Exosome-based vesicles further offer biomimetic advantages of low immunogenicity and natural tissue tropism. In parallel, theranostic platforms integrate treatment with imaging to enable real-time monitoring of drug delivery and tumor response. This review synthesizes mechanistic advances and translational developments in lung cancer nanomedicine, with emphasis on strategies that overcome biological barriers such as hypoxia, extracellular matrix density, and efflux pump activity. Clinical progress between 2020 and 2025 highlights next-generation antibody-drug conjugates, nanoparticle vaccines, and gene-loaded systems, several of which have reached regulatory approval or advanced trial stages. Together, these advances highlight the potential of nanocarriers to transform lung cancer therapy into more precise, personalized, and less toxic interventions.

Cancer immunotherapy has revolutionized oncology by harnessing the immune system to target tumor cells. Cancer vaccines that trigger immune responses specific to tumors are becoming more and more popular among new approaches. Nevertheless, traditional tumour-associated antigens are susceptible to immune tolerance and frequently show low immunogenicity. The revolutionary potential of cryptic and non-canonical antigens as new targets for precision immunotherapy is examined in this review. Due to their enhanced tumor selectivity and ability to evade central tolerance, these unconventional antigens present encouraging options for vaccine development. This review examines the mechanisms underlying their antigen production, advanced technologies for their discovery, and various vaccine platforms, highlighting their potential to drive the next generation of cancer vaccines.