In this study, we engineered pH/glutathione dual-responsive nanoparticles (LP/CC-Cu-Cur NPs) based on a poly-γ-glutamic acid (γ-PGA)/chitosan (CS) core-shell architecture for synergistic chemo/chemodynamic therapy of glioma. The nanoparticles feature a core of CC-Cu-Cur NPs, formed via Cu2+-coordinated self-assembly of caffeic acid-grafted CS and curcumin (Cur), encapsulated within a phenylboronic acid-conjugated γ-PGA shell through pH-sensitive borate ester bonds. Surface modification with lactoferrin conferred brain-penetrating and glioma-targeting capabilities. The resulting spherical nanoparticles had a uniform size of 235.89 nm, a zeta potential of -22.66 mV, and high Cur loading (6.02%) and encapsulation efficiency (83.09%). Upon exposure to the acidic tumor microenvironment, the nanoparticle shell detaches, reversing surface charge from negative to positive, thereby enhancing cellular uptake and mitochondrial targeting. Intracellular glutathione then triggers core degradation, releasing Cur and Cu2+. Cur induces mitochondrial apoptosis, while Cu2+ catalyzes a Fenton-like reaction, converting endogenous hydrogen peroxide into highly cytotoxic reactive oxygen species. In vitro, the nanoparticles showed enhanced blood-brain barrier penetration, efficient lysosomal escape, and potent cytotoxicity against GL-261 cells (IC50 = 18.34 μg/mL) via a synergistic action of Cu2+ and Cur (CI = 0.28). In vivo, LP/CC-Cu-Cur NPs achieved superior brain accumulation and antitumor efficacy, highlighting their potential as a promising strategy for glioma therapy.

A man in his 70s with lung adenocarcinoma (cStage IVA) received POSEIDON-based therapy with durvalumab, tremelimumab and chemotherapy. After six cycles, progressive disease prompted a switch to carboplatin plus nab-paclitaxel. Nineteen weeks after the final immune checkpoint inhibitor (ICI) administration, he developed fatigue and anorexia. Adrenocorticotropic hormone (ACTH) and cortisol were below assay detection limits, and a corticotropin-releasing hormone stimulation test showed no ACTH response, consistent with ICI-related isolated ACTH deficiency. Symptoms improved with hydrocortisone replacement. Five weeks later, he developed diabetic ketoacidosis, with a glucose level of 30.4 mmol/L (reference range, 3.9-6.1 mmol/L) and a ketone level of 6.3 mmol/L (<0.6 mmol/L). HbA1c and urinary C-peptide excretion were 6.9% (4.6%-6.2%) and 1.8 nmol/day (7.5-51.4 nmol/day) respectively. These findings supported a diagnosis of fulminant type 1 diabetes mellitus, considered ICI-related. This case highlights the need for continued vigilance, as immune-related adverse events may develop sequentially even after ICI therapy has ended.

Glioblastoma (GBM) remains a lethal primary brain tumor, in part because therapeutic efficacy is limited by the blood-brain barrier (BBB) and the complex tumor microenvironment (TME). Sonodynamic therapy (SDT), i.e., use of ultrasound to activate chemical sensitizers and generate cytotoxic stress, offers a non-invasive strategy for treating deep-seated intracranial disease, but progress is constrained by the scarcity of validated sonosensitizers and the inefficiency of conventional in vitro screening methods. Here, we introduce a New Approach Methodology (NAM) that couples a neural network-based positive-unlabeled (PU) learning framework with a high-throughput, magnetic field-guided 3D bioprinting platform to accelerate identification and experimental validation of SDT-sensitizing agents. Using curated drug and small-molecule data and RDKit-derived molecular descriptors, the PU classifier identifies candidate ultrasound-responsive compounds without requiring reliable negative labels. We then validate the AI-based predictions in physiologically relevant U-87 MG glioblastoma spheroids that reproduce key TME features, including spatial heterogeneity and a hypoxic core. The NAM identifies two FDA-approved drugs, carboplatin (advanced ovarian cancer) and memantine hydrochloride (Alzheimer's disease), as effective ultrasound-responsive agents. In 3D spheroids, combining low-intensity pulsed ultrasound with either drug significantly reduces viability compared with drug-only controls, and both combinations outperform temozolomide (TMZ), the current standard chemotherapeutic. Time-resolved responses reveal distinct kinetics: memantine produces strong early cytotoxicity (24 h) enhanced by ultrasound, whereas carboplatin shows delayed but pronounced cytotoxicity (72 h), also improved by ultrasound. Together, these results establish an integrated computational-experimental NAM that enables rapid repurposing of approved drugs as SDT sensitizers and provides a scalable framework for advancing GBM therapeutic discovery while reducing reliance on animal studies.

Poor aqueous solubility and low permeability limit the oral bioavailability of Nilotinib, a second-generation tyrosine kinase inhibitor used in chronic myeloid leukemia. Nanosponges prepared using cyclodextrin derivatives offer a scalable and efficient platform for enhancing solubility, controlling release, and improving bioavailability. Therefore, this study aimed to formulate Nilotinib-loaded hydroxypropyl β-cyclodextrin nanosponges to enhance oral absorption.

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Tumor angiogenesis plays a crucial role in breast cancer progression, making angiogenesis-associated pathways attractive therapeutic targets. Computational drug discovery approaches, including virtual high-throughput screening (VHTS), molecular docking, molecular dynamics simulations, and binding free energy calculations, have emerged as valuable tools for identifying and optimizing anticancer compounds. This review evaluates the application of these computational techniques in the discovery of antiangiogenic therapeutic candidates for breast cancer.

Light-activated control over drug activity offers a powerful strategy to improve therapeutic selectivity, yet most photoresponsive systems rely on ultraviolet or short-wavelength visible light with limited tissue penetration. Here we report two ruthenium(II) polypyridyl complexes bearing extended donor-π-acceptor ligands and a photocaged kinase inhibitor, imatinib, that enable efficient drug release under deep-red light (660 nm) irradiation. Systematic photophysical and photochemical studies demonstrate that π-conjugation engineering red-shifts metal-to-ligand charge-transfer absorption while preserving clean photoinduced release of coordinated imatinib from the ruthenium center. In BCR-ABL-positive leukemia cells, these complexes exhibit minimal dark toxicity but pronounced light-dependent cytotoxicity, accompanied by apoptosis and suppression of oncogenic BCR-ABL phosphorylation. Effective activity in 3D tumor spheroids was also observed, confirming efficient penetration and photoactivation in a physiologically relevant model. Together, these results establish a molecular design strategy for developing deep-red-light-activated Ru(II) photocages and highlight their potential for spatiotemporally controlled kinase inhibition in cancer therapy.

Programmed cell death protein-1 (PD-1) inhibitors have transformed cancer therapy, but evidence suggests PD-1 signaling modulates µ-opioid receptor activity, potentially attenuating opioid analgesia. This study evaluated the effect of PD-1-based neoadjuvant chemotherapy (NAC) on perioperative opioid use and pain outcomes following mastectomy with immediate reconstruction.

Preclinical studies suggest that tamoxifen (TAM) may interact with the efflux transporter P-glycoprotein (P-gp); however, its effect on intestinal P-gp activity in vivo remains poorly characterized. This study evaluated intestinal P-gp activity in women receiving tamoxifen therapy using fexofenadine (FEXO) as a probe substrate. Sixteen women receiving tamoxifen (20 mg/day for ≥80 days) and 12 healthy women were enrolled. All participants received a single oral dose of fexofenadine (120 mg), and serial plasma samples were collected over 12 h. Pharmacokinetic parameters were determined by noncompartmental analysis, and plasma fexofenadine concentrations were quantified by LC-MS/MS. Systemic exposure to fexofenadine was lower in women receiving tamoxifen than in healthy women. Geometric mean (95% confidence interval [CI]) AUC0-12h was 646.55 ng.h/mL (523.50-798.52) in the tamoxifen group and 994.77 ng.h/mL (832.21-1189.07) in healthy women, whereas AUC0-∞ was 715.40 ng.h/mL (588.92-869.05) and 1123.66 ng.h/mL (919.98-1372.43), respectively (P < .05). Apparent oral clearance (CL/F) was higher in women receiving tamoxifen (167.74 vs 106.79 L/h; P < .05), whereas elimination half-life was unchanged between groups. The observed pharmacokinetic profile is consistent with reduced oral bioavailability and suggests modulation of intestinal transporter-mediated drug disposition during tamoxifen therapy. These findings may have implications for the disposition of concomitantly administered orally administered P-gp substrates and warrant further investigation in dedicated clinical pharmacology studies.

Hepatocellular carcinoma (HCC) is an aggressive malignancy with frequent recurrence and strong immune evasion. Programmed death ligand-1 (PD-L1) facilitates immune evasion by suppressing T-cell activity. Andrographolide (AD), a natural diterpenoid with anti-inflammatory, antiviral, and immunomodulatory properties, has demonstrated antitumor potential.

To evaluate whether prophylactic oral Lactobacillus supplementation reduces chemotherapy- and radiotherapy-associated diarrhea and helps preserve quality of life (QoL) in adults starting anticancer treatment.

The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase that plays a central role in regulating cell growth, differentiation, and survival. In non-small cell lung cancer (NSCLC) and several other malignancies, activating mutations within the EGFR kinase domain lead to persistent receptor activation and uncontrolled downstream signalling. Over the past two decades, X-ray crystallographic studies and structural data deposited in the Protein Data Bank have significantly enhanced our understanding of EGFR activation mechanisms, mutation-driven conformational changes, and inhibitor binding interactions. This review provides a critical evaluation of structural insights obtained from crystal structures of wild-type and mutant EGFR, with particular focus on clinically important mutations such as L858R, T790M, and C797S. These mutations induce specific alterations in activation loop positioning, αC-helix orientation, and ATP-binding pocket architecture, thereby influencing drug binding affinity and therapeutic response. The structural basis for the evolution of EGFR tyrosine kinase inhibitors-from first-generation reversible inhibitors to mutant-selective covalent agents-is discussed in relation to emerging resistance mechanisms. Although structural characterisation has substantially contributed to rational drug design, the ongoing development of resistance mutations highlights the need to integrate crystallographic data with tumour biology and resistance pathways to achieve more durable therapeutic strategies.

The ubiquitin-proteasome system (UPS) plays a central role in regulating protein homeostasis and degradation. Its dysregulation is closely associated with various diseases, including cancer. S-phase kinase-associated protein 2 (SKP2) is a key E3 ubiquitin ligase component of the UPS. It induces proteasome-mediated protein degradation or modulates substrate function by conjugating K48-linked or K63-linked ubiquitin chains to diverse target proteins. Recent studies have shown that the overexpression of SKP2 in several cancer types is correlated with poor clinical outcomes, underscoring its potential as a therapeutic target. Notably, emerging evidence has expanded the functional repertoire of SKP2 beyond cell cycle control to encompass metabolism, DNA repair, stemness, tumor microenvironment (TME) and immunotherapy response, positioning it as an increasingly attractive target for intervention. In this review, the oncogenic properties of SKP2 and its underlying mechanisms were elucidated in multiple cancer types. Moreover, we systematically summarized future directions for SKP2-targeted therapy.

The decision to rechallenge a patient with immune checkpoint inhibitor-associated acute kidney injury (ICI-AKI) remains one of the most challenging dilemmas in onco-nephrology. Although major guidelines affirm that rechallenge may be considered in selected patients, they uniformly acknowledge a critical gap: no validated tool currently exists to estimate an individual's risk of recurrence. Reported recurrence rates range from 16.5% to 44%, and the survival benefit of rechallenge is inconsistent across studies. In this review, we synthesize recent evidence on risk factors for ICI-AKI recurrence, including clinical parameters (acute kidney injury (AKI) severity, renal recovery status, extra-renal immune-related adverse events (irAEs), concomitant medications, and immune checkpoint inhibitor (ICI) regimen), pathological findings (acute tubulointerstitial nephritis (ATIN) with Banff scoring, and glomerular diseases), emerging biomarkers (urinary C-X-C motif chemokine ligand 9 (CXCL9)-to-creatinine ratio with an optimal cutoff of 269.5 ng/g, and serum soluble interleukin-2 receptor alpha (sIL-2Rα) with a cutoff of ≥1.75× the upper limit of normal (ULN)), genetic markers (the propionyl-CoA carboxylase subunit alpha (PCCA) variant rs16957301), and acute kidney disease (AKD). We translate this evidence into a practical, stepwise risk stratification framework that classifies patients into low-, intermediate-, and high-risk tiers through the sequential integration of clinical, pathological, and biomarker information. The biomarker cutoffs included in this framework-derived from diagnostic studies-are hypothesis-generating in the context of recurrence prediction and require prospective validation before clinical application. For each tier, we provide corresponding recommendations regarding rechallenge decisions, monitoring intensity, and prophylactic immunosuppression, while acknowledging the limited evidence supporting prophylactic corticosteroids in this setting. Finally, we discuss current controversies-including the optimal timing of rechallenge, racial differences that challenge model generalizability, and the unresolved role of prophylactic glucocorticoids-and outline future research priorities organized around clinical validation, biomarker development, mechanistic exploration, and integration of emerging technologies. This framework is designed for immediate clinical application across diverse settings, ranging from resource-limited primary hospitals to tertiary centers. By transforming empirical decision-making into evidence-based, individualized risk assessment, this review aims to guide precision rechallenge management for patients recovering from ICI-AKI.

This study aimed to assess the efficacy and safety of integrating programmed death-1 (PD-1) inhibitors with chemoradiotherapy (CRT) in the treatment of locally advanced nasopharyngeal carcinoma (LA-NPC), explore the optimal sequencing of immunotherapy, and to compare the short-term efficacy of different combination regimens during the induction phase.

For patients with locally advanced esophageal squamous cell carcinoma (ESCC) ineligible for surgery, definitive radiotherapy (RT) is the primary curative-intent treatment, yet outcomes remain suboptimal. The benefit of adding induction immunotherapy combined with chemotherapy prior to RT in this setting is unclear. This real-world study compared survival and safety between induction chemoimmunotherapy followed by RT and RT alone.

Bacillus Calmette-Guérin (BCG) is the standard adjuvant therapy for high-risk non-muscle-invasive bladder cancer (NMIBC); however, a substantial proportion of patients develop BCG-unresponsive disease with limited bladder-preserving options. The objective of this study was to determine whether combination immunotherapy provides superior clinical efficacy and safety compared with single-agent immunotherapy for patients with BCG-unresponsive NMIBC.

Previous studies have shown that locoregional therapy combined with systemic treatment provides survival benefits with manageable safety in patients with intermediate-to-advanced large hepatocellular carcinoma (HCC). However, the optimal treatment strategy for HCC beyond the up-to-7 criteria remains unclear because of the high tumor burden and recurrence risk. This study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) plus microwave ablation (MWA) followed by targeted immunotherapy in patients with HCC beyond the up-to-7 criteria.

In this study, we used Mendelian randomization analysis to explore the causal relationships between drug targets and cutaneous melanoma (CM) and subsequently screened for new drug targets for CM. In addition, we verified whether targeted drugs could inhibit the development of CM in CM cells by suppressing the expression of target genes.

The increasing resistance and adverse effects associated with conventional chemotherapeutic agents such as cisplatin have prompted the investigation of natural compounds that act synergistically with chemotherapy to combat cancer. This study investigates the cytotoxic effects of an aqueous extract of Artemisia vulgaris L. in conjunction with cisplatin on A549 human lung cancer cells. The research analyzes the phytochemical composition of the extract and its potential mechanisms of action by assessing apoptosis and autophagy. Cytotoxicity studies demonstrated a synergistic interaction between A. vulgaris and cisplatin. We utilized molecular docking to examine the interactions of the extract components with critical proteins involved in these processes.

Safety evaluation in first-in-human (FIH) Phase 1 oncology trials is largely descriptive and provides limited quantitative insights. This study characterized the dynamics of platelet count (PLT) and alanine aminotransferase (ALT) concentration in the LP-184 FIH study and explored statistical modeling to support personalized dosing strategies.