Triple-negative breast cancer (TNBC) is associated with a poor prognosis due to insufficient molecular subtyping precision and limited actionable targets. Although metabolic reprogramming underlies TNBC chemotherapy resistance, establishing metabolic subtyping systems and investigating drug sensitivity across distinct metabolic subgroups could provide novel therapeutic avenues for breast cancer management. GSVA (Gene Set Variation Analysis) analysis of metabolic pathways reveals significant differences in TNBC (Triple-Negative Breast Cancer) patients. TNBC patients are classified into four metabolic subtypes through consensus clustering, based on their GSVA values of metabolic pathways. These subtypes are: MS_1, characterised by increased lipogenic activity; MS_2, characterised by increased carbohydrate and nucleotide metabolism; MS_3, a metabolism-active subtype with activation of all types of metabolism; and MS_4, characterised by suppressed metabolic activity across all types of metabolism. We next propose a novel method called MODIN (Multiomics-Driven Drug-Cell Interaction Network), which embeds multi-omics gene information (mRNA expression, copy number variation and DNA methylation) and drug SMILES data into a latent space, and then employs a multi-head attention-based interaction module to accurately predict the LN_IC50 values of 621 drugs in TNBC. Based on MODIN, noteworthy disparities in drug sensitivity emerge between the patient cohorts categorised as MS_2 and MS_3. MS_3 patients show a significantly higher sensitivity to chemotherapy regimens, especially for doxorubicin and docetaxel, while the MS_2 cohort displays marked resistance to these drugs. Our study reveals the metabolic heterogeneity of TNBC, and TNBC patients with increased carbohydrate and nucleotide metabolism exhibit the poorest prognoses and greater resistance to doxorubicin and docetaxel.

High-dose cisplatin (100 mg/m2 every 3 weeks for three cycles), administered with radiotherapy for locally advanced head and neck cancer, is associated with acute kidney injury (AKI) in up to 30% of patients and may compromise treatment intensity in 20%.

The advancement of nanotechnology and the growing demand for environmentally sustainable processes have fueled interest in green synthesis methods. In this research, copper-doped zinc oxide nanoparticles (Cu: ZnO NPs) were synthesized using a microwave-assisted approach, employing a bio-extract derived from Pistia Stratiotes (PS) leaves as a reducing agent. Comprehensive characterization through UV-Visible spectroscopy, PL, FTIR, SEM with EDS, TEM, DLS, XRD and XPS confirmed the formation, optical and structural features of the synthesized NPs. SEM and TEM images revealed spherical and nanorod-like morphologies, with particle sizes ranging from 15 nm to 65 nm and a tendency to agglomerate. Density Functional Theory (DFT) simulations using Quantum Espresso indicated a band gap narrowing to 3.0 eV after copper doping. Biologically, the Cu: ZnO NPs exhibited strong antibacterial activity against Candida albicans (16.3-17.5 mm), Staphylococcus aureus (18.4-21.5 mm), and Escherichia coli (19-21.6 mm). Additionally, the NPs showed promising anticancer potential against SK-MEL-28 melanoma cells, with an IC50 value of 30.53 µg/mL. Overall, this research demonstrates an eco-friendly and efficient route for fabricating Cu: ZnO NPs with significant antimicrobial and anticancer properties, emphasizing their potential for future biomedical applications.

The present study reports, the eco-friendly synthesis of gold nanoparticles (AuNPs) using Equisetum diffusum D. Don. extract, a medicinal plant known for its therapeutic properties. Phytochemicals present in the extract served as reducing and stabilizing agents for synthesizing stable AuNPs with an average size range of 68.8 nm. The biosynthesized AuNPs were characterized using UV-vis spectroscopy, FTIR, XRD, SEM, EDX, and dynamic light scattering (DLS) methods, confirming their stability, morphology, and crystalline nature. The green synthesized ED@AuNPs exhibited promising biological activities, including broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria, with inhibition zones from 24 to 37 mm. The anticancer activity was assessed through an MTT assay against hepatic carcinoma (HePG2) cells, revealing dose-dependent cytotoxicity with maximum inhibition at 200 µg/mL (47.62%). Antidiabetic activity was demonstrated by starch hydrolysis and enzyme kinetics, with significant α-amylase inhibitory activity up to 70.85%, comparable to the standard drug Acarbose. Moreover, antioxidant activity was conformed through FRAP and DPPH assays, indicating strong free radical scavenging activity and reducing ability. The study demonstrates the potential of biosynthesized ED@AuNPs as multifunctional agents with applications in biomedicine, particularly in antibacterial, anticancer, antidiabetic, and antioxidant therapies, offering an eco-friendly and sustainable approach for nanoparticle synthesis.

Hepatocellular carcinoma (HCC) presents a significant global health challenge, marked by high mortality and recurrence. This study investigated the synergistic potential of cisplatin and palbociclib (C + P) against HCC cell lines. RT-qPCR revealed that C + P significantly downregulated HCC-related genes, including Hsp90, β-catenin, and components of the PI3K/AKT/mTOR pathway, compared to cisplatin alone and controls. Western blotting confirmed a reduction in phosphorylated AKT (P-AKT) with palbociclib and C + P, while PTEN, a tumor suppressor, was upregulated in the C + P group. Annexin V-FITC assays demonstrated a substantial increase in apoptosis in palbociclib and C + P treated cells. Cell cycle analysis indicated S and G0-G1 phase arrest with C + P, suggesting a combined cytotoxic effect. Scratch wound assays showed that both palbociclib and C + P significantly inhibited cell migration compared to cisplatin and controls. These findings suggest a promising synergistic effect of C + P in overcoming cisplatin resistance in HCC. However, further research is needed to fully elucidate the complex interactions between these drugs.

Triple-negative breast cancer (TNBC) accounts for approximately 15% of breast cancers and lacks estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), rendering it unresponsive to hormonal or anti-HER2 therapies. Due to its poor prognosis and limited treatment options, there is an urgent need for targeted therapies. In this study, we developed highly adaptable polyamidoamine (PAMAM) dendrimer-based gel nanoparticles with dual-targeting capabilities against urokinase-type plasminogen activator receptor (uPAR) and ribonucleotide reductase R2 (R2). These nanoparticles were designed to target both TNBC cells and cancer-associated stromal cells by leveraging uPA-uPAR interactions and delivering the antisense oligonucleotide GTI-2040 (GTI) against R2. The resulting dual-functional dendrimer gel nanoparticles, GDP-uPA/GTI, demonstrated good biocompatibility, with an average size of ∼16.45 nm. GDP-uPA/GTI enhanced GTI delivery by 3.4-fold in TNBC cells (MDA-MB-231) and by 4.8-fold in stromal cells (HCC2218) compared to GTI alone. It reduced R2 expression by 83.1% and induced ∼30% TNBC cell death. In a TNBC xenograft model, GDP-uPA/GTI significantly inhibited tumor growth by 50.5%. These findings highlight the unique design of the dual-functional dendrimer gel nanoparticles and their dual-targeting efficacy, demonstrating their potential as a promising therapeutic strategy for TNBC.

ROR1 has garnered significant attention as a therapeutic target in oncology due to its critical involvement in cancer malignancy. Several biologics targeting ROR1 have advanced to clinical trials, but the development of selective small-molecule inhibitors remains limited. In our previous work, we identified the indole-based LDR102 as a novel ROR1 inhibitor with promising antitumor efficacy. However, subsequent studies revealed its off-target activity against kinases such as c-Kit, AblT315I, and PDGFRαV561D, alongside suboptimal pharmacokinetic (PK) profiles. To address these limitations, we pursued a systematic optimization campaign focused on LDR102's scaffold. This effort produced a series of 1-methyl-3-(pyridin-3-yl)-1H-indole derivatives, culminating in the discovery of compound 24d. This lead candidate demonstrates exceptional ROR1 inhibitory potency, high selectivity, robust antitumor activity in vitro and in vivo, and an optimized PK profile, marking a substantive advance toward selective ROR1 inhibitors.

Recent clinical trials have demonstrated that neoadjuvant administration of PD-1 + /- CTLA-4 inhibitor is superior to adjuvant PD-1 inhibitors in patients with resectable stage III and IV cutaneous melanoma. However, the generalizability of these results to an unselected patient population treated in routine clinical settings remains unclear.

Ponicidin, a diterpenoid derived from Rabdosia rubescens, exhibits potent antitumor activity. However, its mechanisms against esophageal squamous cell carcinoma (ESCC) remain obscure. This study aims to explore the effects of ponicidin against ESCC and reveal its molecular mechanisms.

Despite the use of therapeutic modalities such as surgery, chemotherapy, and radiotherapy, breast cancer remains a potentially fatal condition for humans. The primary problems with these treatments are their low efficacy and their inevitable side effects to the surrounding healthy tissues. Overcoming these challenges has been achieved through precision therapeutics, where personalized interventions have significantly improved treatment efficacy. However, the development of nanoparticles has largely remained focused on optimizing delivery platforms based on a one-size-fits-all approach. As lipid-based, polymeric, and inorganic nanoparticles are now being engineered with greater specificity, they are increasingly suited for customization-paving the way for truly personalized drug delivery in the era of precision medicine. In this line, the current study focuses on breast cancer, and recent developments in drug delivery. The first part of this review looks at practical difference between precision medicine and precision targeting. It describes breast cancer signaling pathways, highlighting the exciting potential of nanotechnology in cancer drug delivery using precision targeting - an approach closely linked to precision medicine. We also go over how nanostructures can improve the way drugs, genes, and immunotherapy are delivered in the treatment of breast cancer. Lastly, we discuss challenges, solutions, future directions, and possibilities for the practical use of nanotechnology in the treatment of breast cancer, while introducing nano-products based on clinical trials.

An interesting sunlight-driven photodynamic therapy (PDT) has been realized. In this study, we propose a strategy involving an intramolecular electron-donating ligand to develop a high-performance type-I photosensitizer. Specifically, an electron-rich core is flanked by two iridium atoms, facilitating electron transfer and promoting hydroxyl radical generation. The resulting Ir(III) photosensitizer, Q-T, boosts the rapid generation of reactive oxygen species (ROS) under low-intensity laser exposure. Moreover, the type-I ROS ideally suits hypoxic microenvironments, thus demonstrating remarkable PDT against various cell lines, under artificial and natural sunlight. In a skin squamous carcinoma (A431) organoid model, one cycle of treatment of dosing of Q-T followed by sunlight irradiation effectively induces cellular apoptosis and completely eradicates tumor organoids. This approach offers a promising avenue for the efficient PDT of skin cancer utilizing sunlight.

Older adults with advanced cancer are at risk for toxicities and declines in physical function, which can impact their ability to perform instrumental activities of daily living (IADLs, e.g., preparing meals, managing medications, and cleaning). This decline is a key predictor of treatment outcomes and survival in this population. To address this, we conducted a two-arm, randomized trial to evaluate the feasibility of a home-based chair exercise intervention (ChairEx), delivered in-clinic by oncology staff.

Epidermal growth factor receptor inhibitors (EGFRIs) and immune checkpoint inhibitors (ICIs) show promising efficacy in colorectal cancer and head and neck squamous cell carcinoma therapy, especially in combination. However, given the many cutaneous adverse effects (CAE) associated with each, there is concern for overlap and exacerbation of toxicities. EGFRIs are associated with acneiform rashes and paronychia, while ICIs are associated with lichenoid dermatitis and psoriasis. Xerosis, pruritus, and eczema are seen with both drugs. Understanding the CAEs of EGFRI-ICI combination therapy may guide the management of toxicities and improve adherence to life-saving therapy.

The pathogenesis of uterine carcinosarcoma (UCS) remains unclear due to a few mature cell lines. Herein, we established a new cell line, ESCA, from a Chinese woman. Especially, three sublines, named ESCA-2, ESCA-3, ESCA-5, were isolated based on the rate of cells' different sedimentation. All ESCA cells have been subcultured for more than 60 generations. ESCA sublines display different cell morphology and growth characteristics, as well as have different sensitivity to chemotherapeutic drugs. ESCA was most sensitive to paclitaxel and carboplatin, while ESCA-2 was most sensitive to ifosfamide. Besides, ESCA showed severe chromosome karyotype abnormalities and abnormal number of chromosomes. Whole exome sequence showed ESCA and its sublines, as well as tissue block shared similar single nucleotide variants, such as TP53, TRRAP mutations, while relatively large differences in mutational signature abundance. When all ESCA cells were xenotransplanted subcutaneously into BALB/c-nu mice, they developed into tumors that resembled the original tumor with positive AE1/3 and Vimentin in immunohistochemical staining. Interestingly, the transplanted tumor from ESCA-5 proliferated fastest with a relatively low level of glucose uptake evaluated by micro-PET/CT scanning. Taken together, ESCA and its sublines may be valuable tools to explore the molecular mechanism of UCS.

Anti-HER2 monoclonal antibody (mAb) is the standard first-line therapy for advanced HER2+ gastric cancer. However, resistance to anti-HER2 therapy remains a significant clinical challenge. In this study, we identified a novel resistance mechanism to anti-HER2 therapy in gastric cancer and proposed a strategy to enhance therapeutic efficacy by activating T cells. The association between intratumoral immune cells and clinical responses to anti-HER2 therapy in gastric cancer was investigated. Peripheral blood mononuclear cells (PBMCs) were co-cultured with HER2+ gastric cancer cell lines or organoids to study NK cell responses mediated by anti-HER2 mAb. T cells were depleted or activated to assess their impact on antibody-dependent cellular cytotoxicity (ADCC), and the mechanism by which T cells influence ADCC was examined. The combinatorial effects of anti-HER2 mAb and HER2 × CD3 T cell-engaging bispecific antibody (bsAb) in gastric cancer were evaluated. A total of 35 gastric cancer patients receiving anti-HER2 mAb treatment were enrolled. A higher number of intratumoral T cells were associated with greater tumor regression and improved overall survival following anti-HER2 mAb therapy. Mechanistically, T cells, mainly CD4+ T cells, influence NK cell functional and phenotypic changes via interleukin-2 (IL-2) production. Activating T cells by HER2 × CD3 T cell-engaging bsAb enhanced the anti-tumor effects of anti-HER2 mAb in gastric cancer. Our study identified the lack of T cell help as a novel resistance mechanism to anti-HER2 mAb in gastric cancer. Enhancing T cell help via the combination of HER2 × CD3 bsAb improved the therapeutic efficacy of anti-HER2 mAb in gastric cancer.

The side effects and resistance to treatments associated with platinum compounds, such as cisplatin, underscore the present need for novel anticancer agents with improved properties. The development of hybrid drugs, combining two bioactive units, offers a promising approach by synergistically enhancing the biological activity of the two fragments while reducing the resistance of classic drugs. This work presents the synthesis of a novel family of heterobimetallic compounds, featuring a monofunctional Pt(II) complex with amino groups and a p-ferrocenylaniline ligand. Cytotoxic assays reveal that the derivatives with methylated and isopropylated substituted amines exhibit remarkably higher activity against several tumor cell lines compared with cisplatin and the unsubstituted diamino complex. Notably, these methylated and isopropylated complexes demonstrate high selectivity and present high antitumor activity in cell lines where cisplatin is ineffective. Classical molecular dynamics simulations targeting DNA reveal a consistent relation between the extent of distortion of the duplex upon complex coordination and the cytotoxic activity observed in biological assays. According to our simulations, coordination of the heterometallic complexes can produce a significant disruption of the H-bond pattern of the platinated guanine. Moreover, the distortion mechanism induced by the voluminous substituents of the amino ligands entails either the intercalation of the ferrocene moiety, facilitating new hydrogen bonds between originally non-interacting base pairs and new weak attractive stacking interactions between the Pt(II) complex and neighboring nucleobases, or the displacement of adjacent nucleotides from the pairing region toward the solvent environment.

This study aims to evaluate the efficacy of compression therapy in preventing oxaliplatin-induced peripheral neuropathy (OIPN) in colorectal cancer patients.

Immunotherapy is an emerging and effective treatment for cancer. The mRNA-based cancer vaccines enhance the immune response to cancer cells by activating T cells. However, the cytotoxic T-lymphocyte antigen (CTLA-4) receptor signaling inhibits T-cell activation, thereby reducing the effectiveness of the mRNA-based vaccines. Fortunately, the anti-CTLA-4 monoclonal antibody therapy can block CTLA-4 signaling. Nevertheless, the use of anti-CTLA-4 antibodies is also accompanied by immunotoxic side effects. Therefore, an effective and safe medication regimen plays an essential role in the treatment of cancer. First, we develop a mathematical model to describe the interaction of mRNA-based cancer vaccines and anti-CTLA-4 antibodies under the tumor immune microenvironment. Secondly, by employing the method of Markov Chain Monte Carlo (MCMC), the model is parameterized using experimental data, and the simulations are in agreement with experimental results. Finally, the gradient descent method is designed to optimize the medication regimens to inhibit tumor growth and reduce the side effects. Additionally, we find that the anti-CTLA-4 antibody should be administered following vaccination, and the dose of the antibody should positively correlate with the dose of vaccine within a safe range. Our study provides a theoretical basis for the selection of treatment regimens for clinical trials from a mathematical perspective.

Recently, immunogenic cell death (ICD) activated by phototherapy has attracted increasing attention in anticancer immunotherapy. Pyroptosis, a lysogenic and inflammatory form of cell death distinct from apoptosis, is considered to enhance the ICD process in tumor cells. Endoplasmic reticulum (ER)-targeted pyroptosis induced by phototherapy is reported to promote the release of inflammatory cytokines and DAMPs and amplify ICD response as a result. However, specific and stable tracking of the ER is more difficult than that of other organelles. In this work, we introduce a dual-modulation strategy to regulate the effect of ER-targeting unit p-toluenesulfonamide and twisting conjugation motif on the modification of heptamethine cyanine. A dimer dye (T780T-ER) with twisting structure and four p-toluenesulfonamide molecules is ultimately optimized, which can specifically target ER with good stability and efficient Type I PDT capability. Under PDT/PTT stimulation, T780T-ER activates sufficient pyroptosis and causes the release of inflammatory cytokines and DAMPs. In vivo, promoted ICD response and strengthened antitumor immunity are confirmed against the growth of primary and distant tumors. Summarily, this study highlights the importance of a multiple-modulation strategy in developing ER-targeted photosensitizers and proposes a Type I PDT molecule (T780T-ER) as an ER stress-dependent pyroptosis inducer to enhance antitumor immunotherapy.

Sustained increase in intraocular pressure (IOP) following intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in the treatment of retinal disease has been theoretically attributed to aggregation of anti-VEGF in the iridocorneal angle. However, previous studies by our group showed full clearance of intravitreally injected bevacizumab, aflibercept, and ranibizumab. The objective of this study was to further analyze and compare the clearance of these anti-VEGF agents from the eye after a single injection in a rat model.