Immune checkpoint inhibitor-related myocarditis (ICI-M) is increasingly recognized, but real-world data in thymic epithelial tumors (TET) remain limited.

Higher concentrations of human epidermal growth receptor 2 (HER2) may cause chronic kidney disease. We sought to determine if trastuzumab (a HER2 inhibitor) may be kidney protective.

To evaluate the feasibility of incorporating both standard and novel audiological and vestibular assessments into routine oncology care. A secondary objective was to characterize audiovestibular status prior to platinum-based chemotherapy and identify potential risk factors for cochleotoxicity and vestibulotoxicity.

Immune checkpoint inhibitors (ICIs) are an important treatment option in bladder cancer, but clinical trials have demonstrated that they are associated with immune-related adverse events (irAEs), such as rash, hypothyroidism, hyperthyroidism, and others. This study aimed to evaluate real-world evidence of these irAEs using the FDA Adverse Event Reporting System (FAERS).

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal solid malignancies, characterized by aggressive biology and a paucity of effective treatments. Activating mutations in KRAS occur in more than 90% of cases and are fundamental to tumor initiation, progression, therapeutic resistance, and immune exclusion, establishing KRAS as the dominant oncogenic driver in PDAC. Long considered undruggable, KRAS has recently become a viable therapeutic target with the development of allele-specific inhibitors as well as pan-RAS(ON) agents capable of broadly suppressing mutant RAS signaling. Preclinical models and early-phase clinical trials demonstrate meaningful antitumor activity, with emerging evidence of tumor microenvironment remodeling and delayed resistance. Combination strategies integrating KRAS-directed therapies with chemotherapy, vertical pathway inhibition, immunotherapy, and emerging approaches such as KRAS degradation and RNA-targeted approaches are being explored to improve the depth and durability of response. Together, these advances signal a paradigm shift toward molecularly guided treatment strategies in PDAC and offer a promising path forward in a disease with substantial unmet clinical need.

Cantharidin (CTD) is a natural anticancer compound whose clinical application is limited by poor water solubility, low bioavailability, and significant toxicity. To develop a more effective and safer therapeutic strategy, we proposed a synergistic combination therapy by integrating CTD with staurosporine (STS), a protein kinase inhibitor that shares complementary mechanisms of action targeting the mTOR/HIF-1α/VEGF pathway. We further developed an aptamer-guided liposomal nanosystem for the co-delivery of CTD and STS (Apt/CTD-STS/NL), aiming to enhance tumor targeting, improve bioavailability, and reduce the systemic toxicity of both drugs.

Vascular dementia (VD) is a cerebrovascular disease-associated cognitive disorder characterized by chronic neuroinflammation. Cinnamic acid (CA), a natural aromatic carboxylic acid, has been demonstrated to mitigate neurological dysfunction. In this study, a two-vessel occlusion (2-VO) rat model was established, and the rats were treated with CA at doses of 45 mg/kg and 90 mg/kg via intragastric gavage. CA treatment significantly restored cognitive function in 2-VO rats, which was attributed to the reduction of neuronal apoptosis. Furthermore, CA administration downregulated the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the hippocampal tissues, while upregulating the expressions of arginase-1 (Arg-1), found in inflammatory zone 1 (Fizz1), and chitinase 3-like 3 (YM-1). These observations suggest that CA promotes the alternatively activated (M2) polarization of microglia in hippocampal tissues. To simulate the neuroinflammatory environment in vitro, BV2 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) treatment. CA pretreatment promotes M2 polarization in OGD/R-induced BV2 cells, opposing OGD/R-driven M1 polarization in these cells. Importantly, network pharmacology analysis identified poly (ADP-ribose) polymerase 1 (PARP1) as a downstream target of CA. PARP1 expression was upregulated in the hippocampal tissues of 2-VO rats and OGD/R-induced BV2 cells, while CA treatment significantly reduced PARP1 expression. Notably, exogenous PARP1 reversed the CA-induced promotion of the microglial M2 phenotype, as evidenced by increased iNOS expression and decreased Arg-1 expression. In conclusion, CA targets PARP1 to promote the M2 polarization of microglia, thereby alleviating neuroinflammation and contributing to the recovery of neurological function in 2-VO rats.

A series of unsymmetrical azine-linked thiazolo[3,2-a]benzimidazole derivatives (4a-r) was synthesized and structurally characterized. Density functional theory (DFT) calculations, including frontier molecular orbital (FMO) analysis and global reactivity descriptors, supported the preferential formation of the E-isomeric forms. In silico target prediction prioritized cyclin-dependent kinase 2 (CDK2), and molecular docking of representative active members (4b, 4 d, 4p, and 4r) revealed key contacts around Arg83/Pro84 and favorable binding energies ( - 3.91 to -6.20 kcal/mol). In vitro antiproliferative activity against human colon carcinoma (HCT-116) and human hepatocellular carcinoma (HepG2) cell lines identified 4r as the most potent compound (half-maximal inhibitory concentration, IC50 = 5.26 ± 0.37 and 5.03 ± 0.42 µM, respectively), surpassing doxorubicin (IC50 = 7.05 ± 0.49 and 6.42 ± 0.31 µM). Absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction indicated high gastrointestinal (GI) absorption, no blood-brain barrier (BBB) permeation, no P-glycoprotein (P-gp) substrate liability, a bioavailability score of 0.55, and zero pan-assay interference compounds (PAINS) alerts. Overall, the integrated synthetic, computational, and biological results highlight azine-linked thiazolo[3,2-a]benzimidazoles, particularly 4r, as promising CDK2-directed anticancer leads.

A L-type amino acid transporter 1 (LAT1)-compatible, anticancer-active tyrosine-naphthoquinone (NQ) conjugate was successfully developed. The conjugate was designed to exploit LAT1 overexpression in cancers with the goal of achieving selective cytotoxicity for cancerous over noncancerous cells. The tyrosine-NQ molecule was subjected to cell viability, imaging, docking and in silico pharmacological studies along with structure-activity relationship (SAR) assessment. Cell viability investigations included IC50 and substrate-competition studies. Cells of cancerous (PC3) and noncancerous (HEK293) origin with high and minimal expressions of LAT1, respectively, were employed for biochemical investigations. The tyrosine-NQ assembly showed significant cytotoxic selectivity toward PC3 over HEK293, with activity comparable to that of the parent molecule NQ and doxorubicin (DOX), an approved drug. Docking studies demonstrated that the conjugate is LAT1-compatible as it interacts with key residues along the protein's transport pathway. Cell viability competition studies verify a LAT1-facilitated uptake. SAR studies revealed that the conjugate's anticancer activity is due to its aryloxy-naphthoquinone motif. In silico pharmacological investigations determined that the conjugate is leadlike and therefore, well-suited for structural modifications for further drug development. Finally, imaging investigations showed that, with PC3, the conjugate caused drug-induced stress-responses in nuclear morphology. Overall, findings demonstrate that the tyrosine-NQ conjugate is a promising lead for the design of LAT1-targeting, NQ-based chemotherapeutics.

In Japan, amrubicin hydrochloride (AMR) is occasionally administered to patients with recurrent small cell lung cancer (SCLC). AMR therapy can induce febrile neutropenia (FN), a complication that may be fatal or compromise therapeutic efficacy due to treatment interruption or dose reduction. Identifying risk factors for FN is therefore critical to ensuring safe and effective AMR administration. Current evidence on this issue remains limited to small case series, underscoring the need for more robust studies. We conducted a multicenter retrospective analysis to examine predictors of FN during AMR treatment for recurrent SCLC. Patients who received AMR between April 1, 2013, and March 31, 2023, were included. The cohort comprised 256 patients, divided into 192 without FN and 64 with FN. Multivariate analysis demonstrated that performance status (PS) >2 (odds ratio: 5.8, 95% confidence interval: 1.70-19.80, p=0.005) and hematocrit (HCT) (odds ratio: 0.93, 95% confidence interval: 0.877-0.994, p=0.033) were significantly associated with FN development. These findings suggest that PS and HCT may serve as key indicators for predicting FN during AMR therapy in patients with recurrent SCLC.

Myrsine linearis (Lour.) is a medicinal plant in Vietnam that was used to treat various diseases. However, the phytochemical and biological activities of this plant have not been extensively investigated. Therefore, this study extracted the essential oil from Myrsine linearis leaves (MLEO), followed by the identification of phytochemical components and the evaluation of anti-inflammatory and anticancer activities in vitro and in silico. The results showed that major constituents in MLEO were β-caryophyllene (11.3 %), α-humulene (10.3 %), caryophyllene oxide (4.6 %), and spathulenol (4.3 %). MLEO inhibited the protein denaturation (IC50 =34.01±5.64 µg/mL) and inhibited nitric oxide release in LPS-induced macrophage with the value of 33.19±1.78 %. The main compounds in MLEO bound to cyclooxygenase-2 and nitric oxide synthase, with binding energy values ranging from -6.1 to -7.5 kcal/mol, similar to those of positive controls. Additionally, MLEO demonstrated cytotoxicity against different cancer cells, with IC50 values ranging from 20.26±1.1 µg/mL to 21.11±1.41 µg/mL. Therefore, MLEO is a promising candidate for supporting the treatment of diseases relating to inflammation and cancer.

Peritoneal metastasis (PM) from gastric cancer (GC) is associated with poor prognosis and limited treatment options. We investigated a novel peritoneal-targeted therapy using CF33-human sodium iodide symporter (hNIS), a chimeric orthopoxvirus, combined with anti-PD-L1 immune checkpoint blockade in an immunocompetent mouse model of GCPM.

Neuro-ophthalmic complications associated with immune checkpoint inhibitors (ICIs) are rare. These involve adverse events primarily affecting the optic nerve, other cranial nerves, and the neuromuscular junction. Myasthenia gravis-like syndrome (often with concomitant myositis) is the most commonly reported immune-related adverse event, followed by optic neuropathy, of which the most notable is optic neuritis. Symptoms typically present within 6 months of exposure. Prompt and comprehensive evaluation is essential. Diagnostic work-up may include MRI brain and orbits, lumbar puncture, serum, and cerebrospinal fluid antibody testing.

Oral systemic anti-cancer therapies improve convenience, but also shift responsibility for treatment management to the patient. Education, communication, and models of care must adapt to support safe, equitable, and sustainable oral anti-cancer treatment.

Current aromatase inhibitors (AIs) are limited by poor bioavailability and high toxicity, underscoring the need for the development of new therapeutics. In the present study, a series of 12 benzimidazole-pyrazole hybrids was designed, synthesized, and structurally characterized using infrared spectroscopy, mass spectrometry, nuclear magnetic resonance spectroscopy, and elemental analysis. Their anti-breast cancer potential was evaluated against the MCF-7 cell line using the MTT assay. Notably, compounds 5g and 5i exhibited the highest cytotoxicity, reflected by the lowest IC50 values, while showing minimal toxicity toward the normal cell line, NIH3T3. Aromatase inhibitory activity, assessed using the fluorometric assay, further identified compound 5g as the most potent inhibitor. Complementary molecular docking studies demonstrated that compounds 5g and 5i form favorable interactions with the aromatase enzyme, showing higher binding affinity compared to letrozole, providing mechanistic insight into their inhibitory activity. ADMET analysis further confirmed the drug-likeness and pharmacokinetic suitability of the synthesized derivatives. Collectively, these results establish compound 5g as a promising lead for aromatase inhibition, necessitating further in vivo evaluation.

The key epigenetic regulator polycomb repressive complex 2 (PRC2) is dysregulated in multiple cancers. While most therapeutic strategies target its catalytic EZH2 subunit, inhibition of its allosteric EED subunit offers a potential strategy for overcoming emerging drug resistance. Here, we identify and characterize AN-329/11627212, a novel EED-targeting compound, through structure-based virtual screening. Biochemical and biophysical analyses confirm its direct binding to EED. Strikingly, x-ray crystallography reveals that AN-329/11627212 induces dissociation of the pre-bound EED-H3K27me3 complex, consistent with a "hit-and-run" inhibitory mechanism. Detailed molecular docking revealed that AN-329/11627212 embeds itself within EED's allosteric H3K27me3-binding pocket. Functionally, AN-329/11627212 exhibited anti-proliferative activity in PRC2-dependent cancer cell lines, most potently against HCT116 colon cancer cells. Our work identifies AN-329/11627212 as a novel chemotype that acts by dissociating the EED-H3K27me3 complex, providing a foundation for developing next-generation anti-tumor agents targeting PRC2.

Despite the remarkable success of immune checkpoint inhibitor (ICI) therapy in solid tumors, immune-related adverse events (irAEs) have posed great challenges in the whole-course management of ICI immunotherapy. Reliable biomarkers helping to predict irAEs are still limited and lacking.

Tumor dynamic models are vital for evaluating oncology treatments and guiding clinical drug development decisions. However, few studies rigorously assess their predictive capabilities, especially when forecasting tumor trajectories from clinical trials with short or inconsistent follow-up across treatment arms. Poor predictive performance or biases related to follow-up time could potentially limit the general utility of tumor growth inhibition (TGI) models. This study quantitatively evaluates prediction bias across several established tumor dynamic models, comparing five classical pharmacometric TGI models with the deep learning-based Tumor Dynamic Neural-ODE (TDNODE) framework. Using time-truncated clinical trial data from 3106 patients with non-small cell lung cancer (NSCLC) across four completed atezolizumab phase III studies, we consistently observed moderate-to-high positive bias in the predictions from pharmacometric models, particularly with more limited follow-up. By examining the structures of these models and comparing them to observed data, we highlight how the assumed kinetic patterns potentially lead to biased parameter estimation and systemic overestimation of tumor size when applied to immature datasets. In contrast, the TDNODE framework, using deep learning, demonstrated promising early results, exhibiting improved predictive performance in the same evaluations. These findings underscore the critical need to address prediction bias in tumor dynamic modeling with immature data and to consider alternative approaches to established paradigms for certain drug development applications. This study also generally demonstrates the potential of novel methods, such as deep learning, to potentially enhance the reliability of tumor dynamics modeling, especially in challenging early-phase clinical decision-making scenarios.

Chemotherapy-induced nausea and vomiting (CINV) is a common and severe adverse effect of breast cancer (BC) treatment that compromises treatment adherence and quality of life. This meta-analysis aims to assess the prevalence and risk factors of CINV in BC patients, thereby providing clinical insights for its prevention and improvement. Patient/material and methods: Relevant literature was identified through an extensive search of electronic databases from their inception up to July 10, 2025: PubMed, Web of Science, Embase, Cochrane, CNKI, Wanfang, and VIP databases on prevalence rates, odds ratios (OR), and corresponding 95% confidence intervals (CI) were extracted for analysis.

Anticancer peptides (ACPs) are increasingly recognized as promising therapeutic candidates due to their ability to selectively target cancer cells. However, the systematic discovery of novel ACPs, particularly from high-throughput sequencing datasets, remains hindered by technical and methodological limitations. Current prediction frameworks require pre-extracted peptide sequences, involve manual preprocessing, and yield variable results, which restricts their applicability for large-scale, data-driven discovery.