Triple-negative breast cancer (TNBC) remains a therapeutic outlier, with limited targeted options and frequent relapse despite chemotherapy. While platinum therapy can benefit some TNBC cases, including BRCA1/2-mutant tumors, toxicity and limited tumor-selective exposure often restrict its impact. To address these barriers, we applied a lipid-metallodrug prodrug approach and synthesized an oxaliplatin-oleic acid (OXA-OA) conjugate that coupled OXA's cytotoxicity with OA-associated anticancer activity. The prodrug was encapsulated into genipin-crosslinked albumin nanoparticles (OXA-OA Alb NPs) to improve tumor targeting, yielding a uniform size of 140.52 ± 4.35 nm, a PDI of 0.25 ± 0.05, and an encapsulation efficiency of 84.55 ± 4.49%. Spectrometric analysis confirmed successful OXA-OA conjugation. The nanoparticles demonstrated enhanced cellular uptake and tumor targeting. In vitro, OXA-OA Alb NPs reduced the IC50 to 0.19 ± 0.36 µg/mL (4T1) and 0.20 ± 0.16 µg/mL (MDA-MB-231). This corresponded to 25 to 30-fold higher cytotoxicity than free OXA and > 50-fold than OA. Furthermore, apoptosis indices reached 1.47 (4T1) and 1.42 (MDA-MB-231), which were 4.19- and 4.50-fold higher than OA and 2.43- and 2.53-fold higher than OXA. In vivo, OXA-OA Alb NPs achieved ~ 90% tumor inhibition in a TNBC mouse model, with minimal systemic toxicity, stable liver and kidney function, and reduced organ damage compared with other treatment groups. These findings suggest that OXA-OA Alb NPs offer a promising and safer approach for TNBC, with potential for further exploration in preventing metastasis and recurrence.

To mitigate the severe adverse effects associated with the systemic administration of doxorubicin (DOX), this study developed a dissolving microneedles (MN) patch loaded with doxorubicin hydrochloride (DOX-MN) for the local treatment of breast cancer. It specifically investigated the influence and underlying mechanisms of drug loading and application force on drug bioavailability. DOX-MN with intact structure and drug enrichment at the needle tips were successfully fabricated using a centrifugal micro-molding technique. Characterization confirmed the excellent mechanical strength and skin insertion capability of the MN, which dissolved rapidly and released the drug within 30 min. In vivo pharmacokinetic studies identified drug loading and application force as critical determinants of bioavailability. A high drug loading potentially created a local supersaturated state, enhancing drug penetration and achieving a relative bioavailability of 65.25%. Increasing the application force to 25 N effectively minimized drug residue on the skin surface, improving bioavailability by approximately 1.5-fold. In a 4T1 tumor-bearing mouse model, DOX-MN administration facilitated efficient drug enrichment and sustained retention at the tumor site, yielding a tumor inhibition rate (90.61%) comparable to intravenous injection. Safety assessments indicated that using a dedicated applicator significantly reduced skin irritation. This study demonstrates that optimizing drug loading and application force enables efficient local DOX delivery via MN, ensuring potent antitumor efficacy while minimizing systemic toxicity, thereby presenting a promising novel strategy for breast cancer therapy.

We describe a case of febrile neutropenia in a patient with metastatic non-small cell lung cancer, occurring after 36 cycles of nivolumab therapy. A bone marrow aspirate was performed which showed myeloid maturation arrest without a clear alternative cause, supporting an immune-mediated mechanism. The patient responded well to broad-spectrum antibiotics and granulocyte colony-stimulating factor (G-CSF), with successful rechallenge until other immune-related toxicities led to discontinuation. While uncommon, haematological immune-related adverse events are potentially life-threatening, with neutropenia reported in <1% of patients treated with immune checkpoint inhibitors. This case demonstrates three important points: (1) neutropenia may occur even late in the course of treatment with immunotherapy, highlighting the persistent need for vigilance; (2) bone marrow biopsy and the careful review of medications are essential to differentiate immune-mediated from chemotherapy or other drug-related cytopenias; and (3) management requires urgent recognition, antimicrobial cover, and G-CSF, and caution in the consideration of rechallenge.

Increasing survival rates following cancer diagnoses, combined with demographic aging, have resulted in a growing population of long-term survivors. Many of these individuals face persistent and late-onset effects of oncological treatments. This article examines the most common sequelae associated with traditional treatment approaches, presents emerging evidence on innovative therapies, and explores their impact on patients' quality of life.

Accurate prediction of peptide-protein interactions (PepPI) is crucial for advancing peptide-based anticancer drug design. In this study, we introduce ProVenTL, a computer-aided molecular design framework that leverages transfer learning and protein language model embeddings to enhance PepPI prediction accuracy and interpretability. Two complementary strategies were explored: (i) fine-tuning a CAMP model pretrained on large-scale PepPI data from the Protein Data Bank (PDB) using a curated dataset of Calloselasma rhodostoma venom peptides and cancer-related proteins, and (ii) integrating ProtT5 embeddings with stacked autoencoder-deep neural networks (SAE-DNN) and TabNet classifiers. Models were comprehensively benchmarked against baseline configurations and representative deep-learning approaches using standard classification metrics, while biological relevance was evaluated through functional enrichment and pathway analysis of top-ranked predictions. Compared with baseline configurations and conventional deep-learning approaches, the ProtT5-based SAE-DNN model achieved the best performance (accuracy = 0.78; ROC-AUC = 0.86), demonstrating improved generalization capability on a small, domain-specific venom peptide dataset. The model identified key targets such as TRBC2, CD274, HIF1AN, PCSK9, and PLAU, which are associated with pathways involved in immune suppression, hypoxia regulation, lipid metabolism, and metastasis. This study highlights the utility of transfer learning and protein language models for PepPI prediction in data-limited scenarios and establishes a computational framework for prioritizing snake-venom-derived peptides for anticancer drug discovery and future experimental validation.

Activation of the T cell receptor (TCR) complex is fundamental to initiating adaptive immune responses, particularly in CD8⁺ cytotoxic T lymphocytes that mediate anti-tumor immunity. However, the immunosuppressive tumor microenvironment often impairs TCR signaling, limiting the efficacy of T cell-based cancer immunotherapies. Here, we report the identification of rosmarinic acid (RA), a naturally occurring polyphenolic compound, as a potent small molecule enhancer of TCR signaling. RA significantly augments IL-2 and IFN-γ production, promotes T cell proliferation, and enhances cytotoxicity of CD8⁺ T cells in vitro. Mechanistically, RA directly binds to MEK1, a key kinase in the MAPK/ERK pathway, with high affinity, leading to reduced MEK1 phosphorylation and downstream signaling activation. Transcriptomic and metabolic profiling of RA-treated CD8⁺ T cells revealed upregulation of genes associated with TCR signaling, calcium flux, PPAR signaling, and oxidative phosphorylation, indicating a broad remodeling of T cell effector function and metabolism. In vivo, RA treatment significantly suppressed tumor growth, increased tumor-infiltrating lymphocyte (TIL) frequency, and improved survival in MC38 tumor-bearing mice. These effects were abrogated upon CD8⁺ T cell depletion, confirming their central role. Furthermore, RA synergized with anti-PD-1 therapy and enhanced the efficacy of adoptively transferred OT-I T cells in colorectal tumor-bearing hosts. Collectively, our findings reveal RA as a novel immunomodulatory agent that boosts CD8⁺ T cell responses via MEK1-mediated TCR signaling enhancement, providing a promising strategy for drug repurposing in cancer immunotherapy.

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.