Photodynamic therapy (PDT) is a promising therapeutic modality based on the combined use of light and photosensitizers (PSs) and approved for treating several types of cancers. Thio-heterocyclic naphthalimide-based PSs are particularly attractive as phototheranostic agents, combining fluorescence imaging for diagnosis with reactive oxygen species (ROS)-mediated cytotoxicity for treatment. However, no effective conjugation strategy for simultaneously endowing naphthalimides with water solubility and efficient ROS production ability currently exists. Herein, novel water-soluble, heavy atom-free thioxanthene-fused naphthalimide-polyamine conjugates 1-4 have been developed. Structural variation in the polyamine moiety, including chain length and nitrogen content, allowed the fine-tuning of key properties. Conjugates 2 and 3 exhibited (i) favorable photophysical and fluorescent properties, (ii) enhanced water solubility, (iii) improved photodynamic efficacy against MCF-7 breast cancer cells, and (iv) negligible dark toxicity. This novel class of thioxanthene-fused naphthalimide-polyamine conjugates provides a promising conjugation strategy for improving the drug-like properties of PSs.

Drug sensitivity prediction is an important issue within the precision medicine field. IC50, which is the molar drug dose needed to decrease the viability of cells by half compared to the drug-free control, is the main pharmacodynamics parameter used for drug sensitivity analysis in large-scale pharmacogenomics screenings. Computational estimation of IC50s based on molecular and genomic factors significantly reduces costs associated with experiments for measuring cell viability and allows for accelerating the process of drug discovery. Traditional methods of IC50 calculation do not allow integrating the three-dimensional chemical structure of drugs and the biological context of particular cell lines, resulting in suboptimal model performance when using different pharmacogenomics data sources. In this work, we propose an innovative dual-branch approach based on Graph Isomorphism Network (GIN) drug representations coupled with a Multilayer Perceptron (MLP) for 50-dimensional ssGSEA pathway activities calculated from CCLE gene expression. After training on cell-line-drug pair combinations from the Genomics of Drug Sensitivity in Cancer 2 (GDSC2) dataset across various cancers, the proposed GIN+Pathway MLP model attains an R2 of 0.8553 and a Pearson Correlation Coefficient (PCC) of 0.9249 on the testing split of the same dataset. In a variant ablation study of six variants, we find that eliminating the pathway MLP component lowers the R2 value by more than 0.15, thus proving the importance of biological features in the two-branch model. The performance of our proposed model exceeds benchmark scores for models such as GraphDRP (PCC = 0.870, R2 = 0.756) and DeepCDR (PCC = 0.847, R2 = 0.720) when tested on the same GDSC2 dataset.

Innovations in therapeutic modalities and targeted drug delivery are two key approaches to improving the effectiveness of cancer treatment. With the development of therapeutic concepts and nanotechnology, recent research has shifted from tissue- or cell-level drug delivery to organelle-specific delivery to amplify therapeutic effects. Among these organelles, the endoplasmic reticulum (ER) has emerged as a particularly promising target because of its extensive membrane network, which serves as a major site for protein synthesis, lipid metabolism, calcium homeostasis, and intracellular signaling. The disruption of ER function can trigger severe cellular stress and apoptosis, providing a rationale for ER-targeted cancer therapy. However, traditional small-molecule drugs often exhibit poor ER specificity, rapid degradation, and limited intracellular accumulation, significantly restricting their therapeutic potential. In contrast, ER-targeting multifunctional nanoplatforms have demonstrated superior advantages, including enhanced stability, precise localization, controlled drug release, and multimodal therapeutic capabilities. In this Review, we systematically summarize the recent advances in ER-targeting nanotherapeutics and their applications in chemotherapy, phototherapy, immunotherapy, biotherapy, and combination therapy. Furthermore, we discuss the advantages, challenges, and mechanistic insights of these strategies, aiming to provide perspectives on accelerating the clinical translation of ER-targeting precision drugs.

Epithelial-mesenchymal transition (EMT) mediated metastasis remains the primary contributor to cancer-related mortalities worldwide, highlighting the critical need for therapeutic strategies that simultaneously eradicate primary tumors and suppress metastatic progression. However, conventional photodynamic therapy (PDT), particularly oxygen-dependent type-II photosensitizers, suffers from hypoxia-limited efficacy and may even induce EMT under suboptimal treatment conditions. Herein, we report enhanced type-I reactive oxygen species (ROS)-generating nanoparticles (NPs) based on the coassembly of two structurally similar small molecules (TQTT-NO and TQTT-NH), integrating light-controlled nitric oxide (NO) release to synergistically inhibit tumor growth and EMT. By leveraging precise molecular structure matching, the coassembled NPs (TQTT-NO/NH NPs) enable efficient intermolecular electron transfer, as revealed by the photocurrent results and Gibbs free energy calculations, thereby favoring type-I ROS generation under white-light irradiation while simultaneously triggering on-demand NO release. The developed TQTT-NO/NH NPs effectively suppress transforming growth factor-β (TGF-β)-induced EMT, inhibit cancer cell migration and invasion in vitro, and markedly reduce primary tumor growth and lung metastasis in a murine tumor model under light activation. Overall, this work establishes a generalizable molecular coassembly strategy for enhancing type-I PDT and EMT regulation, offering a promising paradigm for next-generation antimetastatic phototherapeutic platforms with translational potential.

Among 15-20 cases of breast cancer, triple-negative breast cancer (TNBC) is the deadliest form of the disease. The most effective form of treatment for this type of cancer is still targeted chemotherapy because it lacks hormone receptors. Myristicin, an active aromatic compound with anticancer properties, is mostly found in nutmeg. Antitumor, antioxidant, and antimicrobial activity are among few of the numerous properties of myristicin. On TNBC cells, the exact modes of action are mostly unidentified. This study shows that myristicin triggered the mitochondria-mediated apoptosis in MDA-MB-231 cells. The MTT assay assessed the anti-proliferative potential of myristicin on TNBC cells (IC50 0.65 mM ± 0.98). Flow cytometry analysis was used to evaluate the myristicin's effects on cell apoptosis using annexin V/PI (46.4 ± 2.31%). After evaluating the protein expression, myristicin significantly decreased the expression of Bcl2 and HSP60 while enhancing the expression of proteins such as caspase 9, caspase 3, bid, bad, caspase 7, P53, cytochrome c, and SDHA. Furthermore, our research confirmed that myristicin has a lower toxicological profile and greater in vivo therapeutic efficacy. In BALB/c mice, 4T1 cells were injected subcutaneously to develop breast tumors, and the mice subsequently received myristicin. According to in vivo results, myristicin treatment reduced tumor weight and volume when compared to the breast cancer control group. Besides, the enzyme analysis, gene, and protein expression showed significant apoptotic properties on myristicin treated group. According to these results, myristicin may be used as a therapeutic approach for the management of TNBC.

Acquired temozolomide (TMZ) resistance remains a major challenge in glioblastoma and may involve the emergence or enrichment of cancer stem cell (CSC)-like characteristics. However, whether stem-like characteristics differ across increasing levels of acquired TMZ resistance remains unclear. This study compared stem-like characteristics among parental TMZ-sensitive glioblastoma cells and two sequentially generated TMZ-adapted populations with different levels of acquired TMZ resistance.

Tumor-resident pathogenic bacteria can promote cancer progression and reduce chemotherapy efficacy, yet strategies to simultaneously target both tumor cells and intratumoral microbes remain limited. Here, we report a poly(2-oxazoline) micelle (POx) platform co-encapsulating paclitaxel (PTX) and metronidazole benzoate (MB) to achieve concurrent delivery of anticancer and antibacterial agents. The POx/PTX/MB micelles produced monodisperse populations with high drug loading efficiency and capacity and remained stable in physiological conditions. In vitro, the co-loaded formulation retained cytotoxic activity against two triple-negative breast cancer (TNBC) cell lines and bactericidal activity against Fusobacterium nucleatum. POx/PTX/MB micelles were well-tolerated at pharmacologically relevant doses in a murine model. This work provides a feasible strategy to integrate antimicrobial therapy with chemotherapy, highlighting the potential of POx micelles as a versatile platform for targeting both cancer cells and tumor-associated pathogens. These findings support further development of combination chemotherapeutic-antimicrobial strategies for tumors harboring pathogenic bacteria.

Aurora-A is a potential therapeutic target in prostate cancer. In this study, virtual screening identified four Aurora-A-targeting peptides, among which Peptide-1 showed the most favourable profile. Molecular docking and MST assays demonstrated that Peptide-1 had the lowest predicted binding free energy and the strongest binding affinity towards Aurora-A (Kd = 0.72 ± 0.04 μM). MD simulation, MM/PBSA, and free-energy landscape analyses indicated that the Aurora-A-Peptide-1 complex was conformationally stable and mainly driven by electrostatic interactions. MTT assays showed that Peptide-1 inhibited the proliferation of PC3, DU145, and NCI-H660 cells, with weaker activity in RWPE-1 cells. Aurora-A knockdown reduced cellular sensitivity to Peptide-1, supporting its target-dependent activity. qRT-PCR further showed increased p53 and p21 mRNA expression after Peptide-1 treatment in PC3/p53WT cells. These findings suggest that Peptide-1 may act as an Aurora-A-targeting peptide with antiproliferative activity in prostate cancer cells.

Extensive-stage small cell lung cancer (SCLC) carries a poor prognosis and has limited therapeutic options. The addition of immune-checkpoint inhibitors (ICIs) to platinum-etoposide (PE) chemotherapy has become an important first-line treatment strategy. However, the comparative benefits and harms of different first-line chemotherapy-based regimens, including ICI-containing combinations, remain unclear.

Cytotoxic chemotherapy remains integral to contemporary uro-oncology despite the rapid expansion of targeted therapy, antibody-drug conjugates, and immunotherapy. Its role is especially critical where therapeutic success depends on maintaining adequate dose intensity, most notably in metastatic testicular germ cell tumours and in cisplatin-based perioperative treatment for muscle-invasive bladder cancer. In metastatic prostate cancer and selected penile squamous cell carcinoma, taxane- and platinum-based regimens also retain clinical value but are constrained by hematologic, neurologic, renal, pulmonary, and gastrointestinal toxicities. This narrative review summarises current evidence and guideline recommendations for Common Terminology Criteria for Adverse Events (CTCAE)-guided management of chemotherapy toxicity across major uro-oncologic disease settings. A practical emphasis is placed on pretreatment risk stratification, cycle-by-cycle surveillance, supportive care, and intent-adapted treatment modification. Across tumour types, early recognition of grade 2 toxicity, urgent management of febrile neutropenia and organ toxicity, and thoughtful preservation of dose intensity when cure is realistic are the central management principles. In older, frail, immunosuppressed, heavily pretreated, or organ-limited patients, CTCAE grades must be interpreted against baseline reserve and cumulative toxicity.

CX-5461 (pidnarulex) is the most clinically advanced small-molecule ligand associated with G-quadruplex (G4) targeting and shows activity in DNA repair-deficient tumors, yet its clinical use is associated with dose-limiting phototoxicity. Here, we repurpose this intrinsic photoreactivity to investigate CX-5461 as a G4-associated, light-activated antitumor scaffold. In solution, CX-5461 produces both Type I and Type II reactive oxygen species (ROS), whereas complexation with G4 DNA markedly decreases detectable singlet oxygen (1O2) formation and favors radical-associated Type I oxidation. This G4-modulated photochemical shift drives oxidative remodeling and destabilization of G4-containing DNA. In cancer cells, photoactivation enhances cytotoxicity by up to two orders of magnitude relative to the dark state and is accompanied by elevated intracellular ROS, increased 8-oxoG formation, γ-H2AX accumulation, and changes in BG4-detected nuclear G4 structures. In vivo, light-activated CX-5461 suppresses tumor growth and extends survival in immunocompetent syngeneic models, eliciting hallmarks consistent with immunogenic genome stress. Collectively, these findings reposition CX-5461 as a clinically relevant scaffold for G4-associated photogenomic cancer therapy, while supporting a model in which broader oxidative DNA damage may also contribute to the biological response.

Autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), affect approximately 2-5% of the global population. They are the most common organ-specific autoimmune disorders worldwide. Growing epidemiological and immunological evidence indicates that AITDs frequently coexist with immune-mediated dermatological diseases. These include atopic dermatitis (AD), psoriasis, alopecia areata (AA), vitiligo, and chronic spontaneous urticaria (CSU). Targeted immunotherapies have become central to the treatment of many immune-mediated skin diseases. Although these therapies are designed to act on specific immune pathways, they may also exert broader systemic immunomodulatory effects. However, thyroid function and thyroid autoantibodies are not routinely assessed in patients with immune-mediated dermatological conditions. This is also true for some patients with known or suspected AITDs. In this narrative review, we summarize the immunological overlap between cutaneous inflammation and autoimmune thyroid disease. We also discuss thyroid-related evidence for IL-4Rα inhibitors, IL-17 inhibitors, JAK inhibitors, IL-12/23 inhibitors, and immune checkpoint inhibitors (ICIs). Current evidence suggests that ICIs have the strongest established association with thyroid dysfunction. In contrast, the thyroid-related effects of dupilumab and ustekinumab are supported mainly by rare case reports. IL-17 inhibitors and selective IL-23p19 inhibitors may theoretically attenuate thyroid inflammatory pathways. However, this possibility has not yet been confirmed in clinical studies. Based on the available evidence, we propose a risk-stratified approach to thyroid surveillance across targeted immunotherapies. Routine thyroid monitoring is most strongly supported for ICIs. For patients at increased thyroid risk, selective assessment of thyroid function and thyroid autoantibodies may also be considered during treatment with dupilumab or ustekinumab. For oral JAK inhibitors, monitoring may be particularly relevant before treatment, during therapy, and after discontinuation because of the potential for immune rebound. Prospective studies are needed to define which patient subgroups would benefit most from thyroid surveillance during targeted immunotherapy.

Leptomeningeal metastases (LM) from melanoma are rare and associated with dismal outcomes. Intrathecal PD-1 antibody therapy has shown encouraging activity in LM. Radiotherapy may enhance tumor immunogenicity and potentially augment immune checkpoint blockade within the central nervous system. The efficacy and safety of combining intrathecal PD-1 antibodies with whole-brain radiotherapy (WBRT) in melanoma LM remain unclear.

Thyroid dysfunction is among the most frequent endocrine immune-related adverse events (irAEs) during PD-1/PD-L1 blockade, but whether baseline thyroid function and treatment-emergent thyroid dysfunction (TeTD) predict pathological response and survival after neoadjuvant immunochemotherapy in locally advanced gastric or gastroesophageal junction adenocarcinoma (LAGC/GEJC) remains unclear.

To analyze the characteristics of adverse drug reaction (ADR) in a specialized stomatology hospital and thus provide references for clinical rational drug use and risk management.

Chemotherapy-induced sensory alterations are common and may negatively affect nutritional status, treatment adherence and quality of life in people with cancer. However, inter-individual variability in these alterations remains poorly understood. This study examined whether personality traits, food neophobia, disgust sensitivity, and sensitivity to reward, contribute to variability in self-reported sensory alterations during chemotherapy.

Echium angustifolium is traditionally valued for its therapeutic properties; yet comprehensive studies on its biological activities are limited. Aerial flowering parts were sequentially extracted with solvents of varying polarity. Extracts were analyzed for yield, phytochemical composition, and total phenolic and flavonoid contents and HPLC. LC-MS/MS analysis in negative ion mode was performed for detailed compound identification. Antioxidant activity was measured using the DPPH assay. Antibacterial activity against Gram-positive and Gram-negative bacteria was evaluated via agar diffusion and MIC/MBC methods. Anti-inflammatory potential was determined in vitro through RBC membrane stabilization (hemolysis) assay. Cytotoxicity and antiviral activity were examined using MTT and cell-based assays on HepG2 and Vero cells. The molecular mechanism of anticancer activity was investigated through qPCR analysis of apoptosis-related genes (Bax, Caspase-3, Caspase-9, and Bcl-2) in HepG2 cells. Antiviral efficacy against Hepatitis A virus (HAV) and Coxsackievirus B4 (CoxB4) was further validated by RT-qPCR quantification of viral RNA copy numbers. The ethanolic extract showed the highest yield (14.23%) among the tested solvents and richest phytochemical profile, with rutin as the predominant compound. LC-MS/MS identified 24 compounds including threonic acid, hypoxanthine, indole-3-carboxylic acid, N-methyllysine, 4-methyl-2-oxovaleric acid, 4-isopropylbenzoic acid, methionine, N-2-fluorenylacetamide, arachidic acid, N-methylanthranilic acid, carbocysteine, fructose-1,6-bisphosphate, lumazine, 5-aminoimidazole-4-carboxamide, and 3-isochromanone. It exhibited significant antioxidant activity (IC50 = 21.08 µg/mL) and antibacterial effects against both Gram-positive and Gram-negative bacteria. It exhibited in vitro anti-inflammatory effects via RBC membrane stabilization (95.5% inhibition at 1000 µg/mL) and dose-dependent cytotoxicity against HepG2 cells (IC50 = 94 µg/mL), while showing low toxicity toward Vero cells (IC50 = 632.24 µg/mL). Mechanistically, qPCR analysis revealed that the extract at IC50 concentration significantly upregulated pro-apoptotic Bax (4.21-fold), Caspase-3 (5.02-fold), and Caspase-9 (4.08-fold), while downregulating anti-apoptotic Bcl-2 (0.33-fold) compared to untreated controls, confirming apoptosis induction through the intrinsic mitochondrial pathway. Antiviral assays revealed significant inhibition of HAV and Coxsackievirus B4 replication at non-toxic concentrations. RT-qPCR quantification demonstrated that the extract at MNTC (250 µg/mL) reduced HAV and CoxB4 viral RNA copies by 50.6% (from 1.22 × 106 to 6.03 × 105 copies/mL for HAV; from 2.47 × 105 to 1.22 × 105 copies/mL for CoxB4), providing direct evidence of viral inhibition. The ethanolic extract of E. angustifolium exhibited multifunctional in vitro bioactivities, including antioxidant, antimicrobial, anti-inflammatory, anticancer, and antiviral effects. LC-MS/MS identified a diverse array of bioactive compounds, while mechanistic studies revealed apoptosis induction via the mitochondrial pathway (upregulation of Bax, Caspase-3, and Caspase-9; downregulation of Bcl-2) and direct antiviral activity through inhibition of viral replication (confirmed by RT-qPCR). These findings validate the traditional medicinal uses of E. angustifolium and highlight its potential as a promising source of bioactive compounds that warrant further in vivo and mechanistic investigations.

The BCL-2 inhibitor venetoclax has transformed outcomes for older or frail patients with acute myeloid leukemia (AML), and its resistance mechanisms are becoming better defined, including compensatory and lineage-associated switches toward MCL-1 or BCL-xL dependence, oncogenic signaling activation, blast phenotype, and differentiation stage. Additional putative mechanisms-such as emerging BAX mutations, mitochondrial structure remodeling, integrated stress response, and metabolic adaptations, including enhanced amino acid uptake and fatty acid oxidation to sustain oxidative phosphorylation-require further validation.

Immune checkpoint inhibitor (ICI)-related parkinsonism is an exceedingly rare neurologic immune-related adverse event (irAE).

Cancer drug response (CDR) prediction is crucial for advancing precision medicine. Advanced computational predictors extracted CDR patterns from multimodal features of cell lines and drugs under the guidance of known CDRs. However, most existing methods struggle to extract biologically meaningful and generalizable CDR representations due to insufficient semantic alignment among the multimodal features. In addition, semantic inconsistencies between multimodal and topological features further hinder the predictive accuracy of CDRs. To address the challenges, a novel Reinforcement Learning-driven Adaptive Synergistic Optimization Network-CDR (RLASON-CDR) is put forward for CDR prediction. RLASON-CDR first constructs multimodal CDR representations aligned within and across drugs and cell lines. Next, it captures high-order topological representations of CDRs from the cell line-drug response network. Finally, a reinforcement learning-based network is proposed to adaptively explore potential CDR patterns by synergistically optimizing these representations instead of semantic fusion. Extensive evaluations demonstrate that RLASON-CDR consistently outperforms existing methods and is robust for predicting unknown CDRs. Gradient attribution analysis further reveals that RLASON-CDR identifies key modality contributions and uncovers biologically response patterns. Furthermore, biological significance analysis indicates that RLASON-CDR can effectively reveal mechanisms of drug response and provide valuable guidance for precision therapy in clinical applications.