The elevated mortality associated with ovarian cancer arises from delayed detection, recurrent disease, and the rapid emergence of chemoresistance. This study assesses the anticancer efficacy of two synthetic curcumin analogues, B-143 and B-155, in comparison to natural curcumin, employing SKOV3 ovarian cancer cells as the experimental model.

Recent studies have shown that while chemotherapy kills tumor cells, it may also induce adaptive changes in cells within the tumor microenvironment, particularly cancer-associated fibroblasts (CAFs), which could paradoxically promote tumor progression. This study aimed to investigate the role of CAFs exposed to paclitaxel (PTX) or doxorubicin (DOX) in tumor progression and explore the underlying mechanisms.

Cancer remains one of the leading causes of mortality worldwide. Dysregulated cellular signaling pathways play a pivotal role in tumorigenesis, tumor progression, and metastasis. Among these, tyrosine kinases (TKs) constitute a critical class of enzymes that catalyze the phosphorylation of tyrosine residues on target proteins, thereby regulating key cellular processes including growth, differentiation, and survival. TKs have revolutionized cancer therapy by selectively targeting these enzymes, resulting in suppressed tumor growth and improved clinical outcomes for patients. Urea-containing motifs represent one of the most important bioactive functional groups in medicinal chemistry. In particular, unsymmetrical alkyl- and benzylureas are widely employed as key structural components in numerous approved drugs. This structural feature enables versatile modifications that enhance physicochemical properties, including solubility, metabolic stability, and bioavailability. This review explores the current landscape of antineoplastic urea-based tyrosine kinase inhibitors, presenting an exhaustive examination of contemporary urea-containing compounds that inhibit TKs while elucidating their mechanisms of action and molecular targets. In recent years, computational technologies have become indispensable in modern drug discovery. They significantly accelerate the identification of new TKIs and support the repurposing of established pharmaceuticals. Ultimately, the review addresses the prevailing challenges and future opportunities in the advancement of urea-containing tyrosine kinase inhibitors.

This study aimed to identify the incidence rate, severity and distribution characteristics of symptoms in ovarian cancer patients during first-line maintenance therapy, and to determine the composition of symptom clusters, so as to provide evidence for clinical medical staff to optimize symptom management strategies for ovarian cancer patients receiving first-line maintenance therapy.

Irinotecan (CPT-11) is a cornerstone chemotherapeutic for advanced colorectal cancer (CRC), but its clinical use is limited by dose-dependent gastrointestinal (GI) toxicity. Xiao-Chai-Hu-Tang (XCHT), a classical traditional Chinese medicine formula, alleviates CPT-11-induced adverse effects, yet its mechanism remains unclear. This study established a CPT-11-induced intestinal toxicity model in CRC rats, using multi-omics analyses (16S rRNA sequencing, fecal metabolomics, SCFA quantification) and an antibiotic depletion model to explore XCHT's mechanism via the gut microbiota-metabolite axis. XCHT significantly alleviated intestinal toxicity, reduced inflammation, and restored intestinal barrier integrity. It also enhanced antitumor immunity, as evidenced by an increased CD4⁺/CD8⁺ ratio and promoted Th1 polarization, and potentiated CPT-11's antitumor effects. XCHT alleviated CPT-11-induced dysbiosis of key bacterial genera and substantially restored the disturbed metabolome, with the restored metabolites primarily enriched in unsaturated fatty acid biosynthesis and linoleic acid metabolism. It also restored SCFA levels and upregulated colonic SCFA receptors/transporter. Correlation analysis revealed that these microbial and metabolic shifts were closely associated with the improvement of intestinal toxicity and antitumor immunity, and XCHT's protective effects depended on an intact gut microbiota. In conclusion, XCHT mitigates CPT-11-induced intestinal injury and enhances immunity by restoring gut microbiota balance and metabolic reprogramming, providing scientific evidence for its clinical use as a complementary therapy for CRC patients on CPT-11.

Fusobacterium nucleatum (Fn) drives chemotherapy resistance in colorectal cancer (CRC) by activating hypoxia-mimicking signaling pathways, yet the molecular mechanisms linking Fn to 5-fluorouracil (5-FU) resistance remain unclear. We investigated how Fn-induced hypoxia-related gene expression contributes to 5-FU resistance and identified a pharmacological strategy to overcome it.

Chemotherapy scheduling poses a challenging control problem due to the need to suppress tumour growth whilst maintaining systemic toxicity within clinically acceptable limits. This study develops a double Q-learning-based controller for optimising daily dosing of a three-drug regimen consisting of cisplatin, docetaxel and irinotecan. A pharmacokinetics-pharmacodynamics (PK/PD) tumour model with eight resistance states is used as the simulation environment. The controller aims to minimise tumour burden whilst enforcing strict toxicity constraints aligned with clinical dosing guidelines. Simulation results show that double Q-learning substantially outperforms classical Q-learning, achieving near-complete tumour suppression within the simulation framework, corresponding to a residual tumour fraction on the order of 10-6 (approximately six orders of magnitude reduction) whilst maintaining toxicity within predefined constraints. Robustness analyses under physiological parameter variations of up to ±50% and under abrupt disturbance events further demonstrate that the double Q-learning policy preserves stable closed-loop behaviour within the simulation environment and exhibits strong resilience to uncertainty. Overall, the results indicate that double Q-learning provides a proof-of-concept framework for adaptive chemotherapy optimisation, with potential for future investigation in reinforcement learning-based chemotherapy optimisation frameworks.

Bispecific antibodies (BisAbs) have transformed the management of relapsed and refractory multiple myeloma (MM), achieving high response rates in heavily pretreated patients. However, these therapies induce profound immune perturbation, including plasma cell aplasia, hypogammaglobulinemia, and T-cell exhaustion, predisposing patients to serious infections. Progressive multifocal leukoencephalopathy (PML) has rarely been reported in this setting.

Gastric cancer is among the most common cancers and represents a major public health problem worldwide. New therapeutic strategies and drugs are needed. Anti-angiogenic agents targeting the Vascular Endothelial Growth Factor (VEGF) are used in combination therapy in the clinic, although their efficacy remains modest. We believe that these large anti-VEGF antibodies could be advantageously replaced by smaller peptides with better tissue penetration. In this study, we evaluate the efficacy of a previously described dimer peptide ligand of VEGF, D6, in inhibiting the proliferation of gastric cancer cells and the growth of the corresponding murine xenograft. The activity of the D6 peptide in these assays was comparable to that of bevacizumab, the positive control antibody, although the peptide required repeated injections at higher molar concentrations. These promising results justify the continued optimization of the peptide dimer, currently under investigation in our laboratory.

This review examines cardiovascular complications of multiple myeloma and anti-myeloma therapy, emphasising integrated systems-based cardiovascular management and the institutional model developed at the University College London Hospital Cardio-Oncology (CO) Centre of Excellence.

Dihydropyrimidine dehydrogenase (DPD), which is encoded by the DPYD gene, plays an important role in the metabolism of fluoropyrimidine (FP) drugs, including tegafur, in S-1. A decrease in DPD activity can cause severe FP-related toxicity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for FP and DPYD polymorphisms recommend FP dose adjustments based on the four major DPYD polymorphisms. However, multiple rare variants of DPYD have been reported. We present the case of a man in his 50s with cT3N0M0 tongue squamous cell carcinoma who developed severe myelosuppression and diarrhea after the initiation of S-1 (tegafur/gimeracil/oteracil) despite appropriate dosing. On day 20 of treatment, the patient developed grade 4 neutropenia and septic shock and required ICU admission. Genetic testing identified a rare heterozygous DPYD variant (c. 812delT) that causes a frameshift and a presumed loss of enzyme function, suggesting an underlying cause of the severe adverse events. Although severe toxicity occurred, marked tumor shrinkage allowed for less invasive surgery. This case highlights the need for expanded genetic screening beyond the guideline-listed variants, particularly in Asian populations, where common variants differ. Combining genotypic and phenotypic evaluations of DPD activity may improve the prediction and prevention of FP-related toxicities, supporting safer and more effective use of FP drugs.

We reported LINGO1 as a potential marker on Ewing sarcoma cells that could enable targeted drug delivery, improving treatment effectiveness while reducing side effects.

BRAF inhibitors have advanced treatment for patients with BRAF-altered high and low-grade glioma (HGG and LGG, respectively). Clinically-available therapies are effective but require selection by mutation type and careful, proactive toxicity management to maximize patient quality of life and treatment duration. While pediatric LGG patients often experience durable responses, adults with LGG and patients with HGG frequently develop treatment resistance and disease progression while on treatment. Strategies to prevent or overcome resistant disease are under active preclinical and clinical investigation. This review serves as a primer to BRAF-altered therapy in glioma, outlines best practices for using available BRAF inhibitors, and highlights emerging therapeutic approaches aimed at improving outcomes in resistant disease. It serves as a forward-looking, practical guide for clinicians treating patients with BRAF-altered glioma.Article highlightsBRAF inhibitors are effective in both pediatric and adult low- and high-grade gliomas (LGG and HGG), but treatment should be tailored to the specific BRAF alteration (Table 1).Dabrafenib combined with trametinib is FDA-approved for BRAF V600E-mutant gliomas, while tovorafenib is approved for pediatric LGGs harboring BRAF V600 mutations or BRAF fusions.Proactive management, including anticipatory guidance and dose reduction for some patients, is essential to mitigate toxicity and avoid treatment interruptions.Tumor progression can occur during treatment interruptions or drug cessation; however, some patients may respond to BRAF inhibitor rechallenge.Emerging strategies focus on combination with other therapies including radiation, autophagy inhibitors, additional targeted agents, and others to overcome acquired resistance.Next-generation BRAF inhibitors-including paradox breakers, dimer disruptors, and protein degraders-are under clinical investigation (Table 2).

FTA is a new FT derivative developed by our team by modifying FT with aspirin, and it has been shown to boost anti-breast cancer activity.

Breast cancer is often treated with tamoxifen, a drug that can cause ocular side effects, including toxic retinopathy. Multimodal imaging, particularly optical coherence tomography (OCT), has improved the detection of early lesions such as foveal pseudocysts, thus increasing the prevalence of this complication. We present a case of tamoxifen-induced retinopathy in a patient treated for four years who developed decreased visual acuity with irreversible retinal lesions in the right eye despite discontinuation of the treatment. OCT was essential in characterizing the lesions. The pathophysiology remains poorly understood, but involvement of Müller cells and glutamate accumulation in the retinal pigment epithelium are suspected. Toxicity depends on cumulative dose, duration of treatment, and individual factors. Initial ophthalmologic screening and regular OCT monitoring are recommended to detect retinal damage early. In case of lesions, substitution with an aromatase inhibitor is often considered to limit lesion progression and preserve vision.

Childhood cancer survivors (CCSs) are at increased risk of cancer therapy-related cardiac dysfunction following anthracycline chemotherapy. Although left atrial (LA) strain assessed by speckle-tracking echocardiography has emerged as a sensitive marker of diastolic dysfunction, it remains unclear when during survivorship LA dysfunction becomes detectable in CCSs treated with anthracyclines.In this retrospective observational case-control study, 92 CCSs (aged 4-32 years) and 96 age-matched healthy controls underwent echocardiography. Participants were stratified into three age groups (4-12, 13-18, and 19-32 years). LA reservoir, conduit, and pump strains were measured using two-dimensional speckle-tracking echocardiography from the apical four-chamber view. Conventional echocardiographic parameters, including mitral inflow velocities (E and A waves), E/A ratio, and tissue Doppler-derived e' and E/e', as well as left ventricular longitudinal strain (LVLS), were assessed.Conventional diastolic parameters did not significantly differ between CCSs and controls within corresponding age groups. However, in young adult CCSs (19-32 years), all three components of LA phasic strain (reservoir, conduit, and pump strains) were significantly reduced compared with age-matched controls. LVLS was also significantly lower in this group, whereas younger CCSs showed no significant differences in LA strain.LA phasic dysfunction was most evident in young adult CCSs despite preserved conventional diastolic indices, suggesting that age-stratified LA strain assessment may help identify survivorship stages at which atrial dysfunction becomes detectable.

Patients diagnosed with metastatic or recurrent cancer experience uncertainty and distress; however, their consultation needs remain insufficiently quantified. We conducted a web survey in Japan (January 23-29, 2025) among adults (≥18 years) with a history of metastatic or recurrent cancer (n=522). Participants selected concerns from 21 items across four domains, and for each endorsed concern, they indicated whether they wished to consult hospital and/or community pharmacists; consultation intention was calculated among those endorsing each item. Hospital-community differences were evaluated using McNemar's test or Mid-P exact test using a significance threshold of p<0.001. The mean age was 58.9±12.9 years; cancers were colorectal (22.2%), breast (18.2%), lung (11.9%), and gastric (11.1%). 88.7% reported at least one concern. The most common concerns were treatment-related side effects (51.0%), anticancer drug mechanism/efficacy (46.9%), treatment costs (42.1%), mental distress (35.1%), and medications used to alleviate cancer- or treatment-related physical discomfort (34.7%). Consultation intention was higher for hospital than community pharmacists for issues including side effects (43.2 vs. 16.2%), mechanism/efficacy (42.9 vs. 18.0%), and symptom-relief medications (48.6 vs. 24.9%). Although concerns regarding medications other than cancer treatment were uncommon (<10% each), consultation intention exceeded 40% when present. These findings indicate that patients with metastatic or recurrent cancer may perceive different consultation roles for hospital and community pharmacists, particularly according to the type of concern. Because these results are based on self-reported consultation intentions rather than actual consultation behavior, they should be regarded as hypothesis-generating and as a basis for future studies on coordinated pharmacist support.

Managing adverse events is important for optimizing cancer treatment and ensuring high patient satisfaction. Studies have assessed (1) anti-epidermal growth factor receptor (EGFR) monoclonal antibody-induced skin toxicities, (2) development of severe neutropenia by renally excreted anticancer drugs in patients with renal impairment (RI), and (3) pharmaceutical care in the treatment of immune checkpoint inhibitors (ICIs). We identified liver metastasis as a risk factor and preemptive systemic antibiotic administration with anti-inflammatory effect as a preventive factor for grade ≥2 overall skin toxicities in anti-EGFR treatment for metastatic colorectal cancer (mCRC). Additional prophylactic topical steroids to systemic minocycline significantly prevented grade ≥2 rashes, but did not mitigate overall skin toxicities. Patients receiving trifluridine/tipiracil (FTD/TPI)-based chemotherapy for mCRC were assessed, resulting in significantly higher early severe neutropenia development among patients with RI. Additionally, we assessed the impact of RI on severe neutropenia development in carboplatin+pemetrexed-based chemotherapy for thoracic cancer. Consequently, severe neutropenia in the first cycle and all-treatment cycles was significantly more confirmed in patients with RI. We assessed the usefulness of pharmaceutical interventions in ICI treatment, which suggested that pharmaceutical care may improve quality of outpatient ICI treatment, and pharmaceutical intervention during the first three months after initiation of ICI treatment is crucial. Our studies have found clinically important outcomes that support the provision of less onerous chemotherapy.

Five undescribed nupharidines, namely amidonupumones A-C (1-3), amidonupumol A (4), and dinupharolutine (7), along with twelve known analogues (5, 6, 8-17) were isolated from Nuphar pumila. Their structures were elucidated by extensive spectroscopic data, ECD, NMR calculations, and X-ray diffraction. Among them, compounds 1-4 represent the first alkaloids containing an amide structure isolated from N. pumila. In vitro bioassays revealed that compounds 7 and 11 exhibited broad-spectrum cytotoxic activity at a concentration of 40 μM.

Melanoma remains one of the most aggressive forms of skin cancer, with limited therapeutic options and significant treatment-related toxicity. In this study, we evaluated the biological activity of a novel dibenzoylmethane derivative, IDPIP, focusing on its cytotoxic, anti-migratory, and pro-apoptotic effects in melanoma cells. IDPIP exhibited pronounced and selective cytotoxicity in murine and human melanoma cell lines, with significantly lower toxicity to non-tumor cells. Notably, IDPIP demonstrated greater potency and selectivity than a clinically used chemotherapeutic agent, with a selectivity index of 23.44, indicating a more favorable therapeutic window. Morphological and flow cytometric analyses revealed that IDPIP induces apoptosis in a dose-dependent manner (up to 90% mortality), involving activation of both intrinsic and extrinsic pathways, as evidenced by caspase-9 and caspase-8 activation assay, respectively. In addition to its cytotoxic effects, IDPIP impaired melanoma cell migration and invasion in vitro, as demonstrated by PMA-induced wound-healing and transwell assays. Treated cells exhibited morphological alterations consistent with reduced adhesion and cytoskeletal disruption. IDPIP treatment was also associated with the accumulation of autophagy-related vesicular structures in this process. Furthermore, using optical tweezers, we demonstrated that IDPIP is capable of interacting with the minor groove of double-stranded DNA. This interaction may contribute to cellular stress responses associated with apoptosis and impaired cell motility. In summary, IDPIP exhibits selective cytotoxicity, promotes apoptosis, and impairs melanoma cell migration in vitro, supporting its potential as a promising candidate for further investigation. Additional studies, including evaluation of DNA damage response pathways and in vivo models, will be necessary to fully elucidate its mechanism of action and therapeutic relevance.