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.

To develop and qualify a physiologically based pharmacokinetic (PBPK) modeling strategy for mithramycin (MTM) and its analog, MTMSA-Trp, with the aim of projecting first-in-human plasma pharmacokinetics and supporting the translational development of MTMSA-Trp for Ewing sarcoma treatment.

Sorafenib remains a systemic treatment option for advanced hepatocellular carcinoma (HCC), but its clinical efficacy is limited by rapid development of adaptive cellular responses that promote cell survival and phenotypic plasticity. Store-operated calcium entry (SOCE) is a key regulator of intracellular calcium signaling and has been implicated in proliferation, apoptosis, migration, and epithelial-mesenchymal plasticity in cancer. This study investigated the association between SOCE and early adaptive responses to sorafenib in Huh7 HCC cells.

Cetuximab sarotalocan is an innovative photoimmunotherapy agent for cancer treatment, with an unclear safety profile. We analysed the clinical adverse event profile of cetuximab sarotalocan in photoimmunotherapy.

Despite major advances in nanomedicine, therapeutic efficacy remains constrained by unfavorable host responses that influence nanotherapeutic retention, biodistribution, and activity. Biological strategies capable of enhancing nanomedicine performance through modulation of host-response pathways, rather than additional nanoparticle engineering, remain largely unexplored. Herein, we investigated whether a microbial levan produced by Weissella paramesenteroides could potentiate the therapeutic activity of a PEGylated β-cyclodextrin-capped benzimidazole-curcumin nanocomplex (BMPE-Cur) in an Ehrlich ascites carcinoma (EAC)-induced hepatic tumor model. Pharmacokinetic, biochemical, histopathological, angiogenic, immunological, molecular, and computational analyses were performed to evaluate therapeutic efficacy and explore underlying mechanisms. The co-administration of levan increased hepatic BMPE accumulation by 2.3-fold and significantly enhanced the therapeutic efficacy of BMPE-Cur, improving survival to 95.45% compared with 60.66% mortality in untreated tumor-bearing mice. Combination therapy produced 86% inhibition of angiogenesis, markedly suppressed tumor-associated biomarkers, oxidative stress, inflammatory mediators, and immunosuppressive cell populations, and restored hepatic function. These effects were accompanied by reduced expression of components of the TLR2/MyD88/NF-κB pathway, including an 80.05% reduction in MyD88 and a 78.93% reduction in NF-κB, together with 6.59-fold and 7.45-fold increases in FXR and FGF15 expression, respectively. Molecular docking supported potential interactions of BMPE, curcumin, and levan-derived structural motifs with TLR2, while isobolographic analysis demonstrated predominantly synergistic interactions across multiple biological endpoints. These findings support the potential of microbial levan as a promising biological potentiator of nanotherapeutic efficacy, with concurrent enhancement of hepatic nanocomplex retention and coordinated immunometabolic remodeling. More broadly, microbial exopolysaccharides may represent a promising class of host-response modulators, supporting a therapeutic paradigm in which optimizing the biological environment may complement conventional nanocarrier engineering to improve the performance of cancer nanomedicine.

Orally administered small-molecule programmed death ligand 1 (PD-L1) inhibitors may have the potential to improve patient outcomes in the treatment of a range of cancers compared with their antibody-based counterparts. A small molecule might achieve better tumor tissue penetration, and oral administration could significantly improve convenience and access for patients.

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.