Adjuvant endocrine therapy is a cornerstone in managing estrogen receptor-positive early breast cancer but may adversely affect metabolic health, including weight gain, insulin resistance, and dyslipidemia. These changes increase the risk of cardiovascular disease and may influence breast cancer outcomes. However, the timing and magnitude of early metabolic changes following endocrine therapy initiation remain poorly characterized. Conventional definitions such as metabolic syndrome rely on dichotomous thresholds and may lack sensitivity to detect early treatment-related metabolic changes, highlighting the need for refined assessment approaches.

Metabolic reprogramming is a fundamental hallmark of cancer progression. However, the oncogenic mechanisms underlying serine metabolism and its impact on chemotherapeutic sensitivity in gastric cancer (GC) remain poorly defined. Here, through integrated metabolomics and 13C-labeled metabolic flux analysis, we identify marked dysregulation of serine metabolism in GC, primarily driven by increased expression of phosphoglycerate dehydrogenase (PHGDH). Mechanistically, we show that with no lysine kinase 1 (WNK1) phosphorylates PHGDH at Ser349 and Ser371, enhancing its enzymatic activity and protein stability by preventing ubiquitin-mediated degradation. In vivo, WNK1 knockout mice exhibit significantly reduced gastric tumor burden, accompanied by decreased serine levels and disrupted redox balance, supporting the protumorigenic role of the WNK1-PHGDH axis. Clinically, enhanced PHGDH activity, elevated serine levels, and increased glutathione abundance are strongly associated with poor oxaliplatin response in GC patient cohorts, suggesting PHGDH as a potential predictive biomarker for chemotherapy resistance. Together, these findings delineate a WNK1-PHGDH-driven serine metabolic reprogramming axis that promotes redox adaptation and chemoresistance in GC, highlighting its dual value as a mechanistic driver and a therapeutic vulnerability in cancer treatment.

This study elucidates the antioxidant, anticancer, and antidiabetic properties of various extracts from Brassica oleracea var acephala (labeled K-29), specifically hexane (BraH), chloroform (BraC), ethyl acetate (BraE), and methanol (BraM) fractions. Antioxidant efficacy was determined through DPPH, ABTS, and FRAP assays, demonstrating a polarity-dependent increase in activity. Among the tested extracts, BraM exhibited most pronounced antioxidant activity, with IC50 values of 49.32 µg/mL, 60.10 µg/mL, and 67.73 µg/mL in DPPH, ABTS, and FRAP assays, respectively, achieving inhibition rates of 92.14%, 90.33%, and 88.35%. BraE displayed moderate antioxidant potential (71.25 µg/mL to 97.64 µg/mL), while BraH exhibited the lowest activity (170.88 µg/mL to 263.29 µg/mL). Antiproliferative activity was assessed against A549 and HeLa cell lines, with BraC showing the most potent cytotoxic effects, as reflected by GI50 values of 65.09 µg/mL and 37.00 µg/mL for A549 and HeLa cells, respectively. The antidiabetic potential of K-29 was further evaluated via α-amylase and α-glucosidase inhibition assays, where the aqueous extract demonstrated the highest inhibition rates of 85.08% and 89.55%, respectively, followed by BraM (71.52% and 81.86%), while BraE exhibited minimal inhibitory activity. These results underscore the therapeutic promise of Brassica oleracea extracts as potent natural antioxidants, anticancer agents, and antidiabetic interventions.

Spirooxindoles represent a distinguished category in medicinal chemistry. Their three-dimensional structure enhances interactions with many biological targets. They exhibit anticancer, antibacterial, antiviral, anti-inflammatory, antioxidant, and antidiabetic properties. Various methods were applied to synthesize spirooxindoles and their derivatives. This review focuses on different synthetic approaches, pharmacological activities, and molecular insights of spirooxindoles that have been published in the first quarter of the twenty-first century. Furthermore, research gaps were highlighted, such as the lack of in vivo validation, toxicity profiling, and standardized yield/replicability data. Twelve synthesis procedures were statistically compared. A total of 40 studies were pharmacologically summarized, and their molecular insights were highlighted.

The KRAS p.G12D variant occurs in 5% of patients with non-small-cell lung cancer (NSCLC) and is the most common substitution variant in pancreatic ductal adenocarcinoma, occurring in 40% of patients, but no targeted therapies directed against this variant are currently approved for clinical use. Setidegrasib (ASP3082) is a first-in-class KRAS G12D-targeted protein degrader.

This study aimed to investigate the anticancer, potential antiepileptic agents, and antioxidant potentials of 10 methyl-substituted halogenated and methoxy conduritols, which had been previously synthesized and characterized. The presence of active functional groups within their structures suggested their potential as bioactive molecules. Both in vitro and in silico approaches were employed to assess their biological activities and therapeutic relevance.

Liquidambaris Fructus can play an anti-tumor role by triggering cell cycle blockade and apoptosis and inhibiting cancer cell proliferation.

Limited data are available on the midterm outcomes of combination therapy with immune checkpoint inhibitors and VEGFR-TKIs (IO-TKI) for advanced renal cell carcinoma (RCC) in real-world settings.

Bleomycin (BLM) is a cytotoxic antibiotic used in veterinary oncology, primarily in electrochemotherapy (ECT), a local ablative therapy where electric pulses increase drug uptake in tumours. BLM is administered intravenously or intratumourally, with the standard intravenous dose for dogs being 15,000 IU/m², followed by electric pulses 8-10 minutes later. This protocol is derived from human oncology and lacks extensive pharmacological data in dogs. We studied BLM pharmacokinetics in 29 dogs with various tumours treated with intravenous BLM and ECT between 2017 and 2023. Samples were collected from serum of 15 dogs, serum and tumours of 8 dogs, and tumours of 6 dogs. The mean volume of distribution (Vd) of BLM was 224.5 ± 75.02 ml/kg, clearance (CL) was 7.04 ± 2.05 ml/kg/min, and area under the curve (AUC) was 65.87 ± 2.11 µg·min/l. The half-life (t₁/₂) of BLM in dogs was 22.03 ± 0.88 minutes. No significant difference was found in tumour BLM concentrations between 8 minutes post-administration and 2 minutes after pulse completion. These results support the recommended 8-28-minute window for applying electric pulses following intravenous BLM administration and may indicate no need for dose adjustments based on body weight or age.

Cancer prognosis has steadily improved over recent decades. In 2025, approximately 85% of patients with cancer were in remission. The growing complexity of oncologic treatments has led to substantial gains in progression-free survival, albeit at the cost of increased cardiotoxic risk. Cardiotoxicity most commonly manifests as heart failure or left ventricular dysfunction. Consequently, the cardiovascular mortality of individuals treated for childhood cancers, as well as of older women treated for breast cancer, now equals or even exceeds oncologic mortality.In response, the European Society of Cardiology has issued its first cardio-oncology guidelines, establishing precise thresholds for left ventricular ejection fraction, longitudinal function (as assessed by echocardiographic strain parameters), and selected cardiac biomarkers. Within this framework, it is crucial to develop robust strategies to predict, enable early detection of, and ideally prevent treatment-related adverse cardiac effects. Rigorous control of traditional cardiovascular risk factors remains the cornerstone of preventing oncology-treatment-induced cardiotoxicity.

Belinostat (PXD101), a hydroxamate-class histone deacetylase inhibitor (HDACi), was approved by the US FDA for patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This review covers belinostat's pharmacological characteristics (including its mode of action), pharmacokinetics, toxicity, drug interactions, and analytical methods. Belinostat inhibits HDACs from Classes I and II, which then raises the acetylation of both histone and nonhistone proteins, resulting in growth cycle arrest and ultimately leading to the death of the malignant cells. The pharmacokinetics of belinostat include a brief elimination half-life and substantial first-pass metabolism in the liver, mostly via UGT1A1. Belinostat's efficacy has been proven in numerous clinical trials, which also revealed a certain level of cytotoxicity specific to tumor cells. Belinostat and its potential metabolites have often been qualitatively and quantitatively estimated and tracked using several analytical methods including UPLC-MS/MS, HPLC-UV, FTIR, TLC, NMR, and ESI-MS. In terms of therapeutic use of belinostat, this review demonstrates how important it is to understand the metabolism and degradation pathways of belinostat, as well as possible drug-drug interactions.

Post-marketing evaluation of lower-dose regimens is critical for optimizing individualized oncology therapy. Venetoclax (VNX) is approved for the treatment of hematological malignancies at doses of ≥400 mg once daily following a ramp-up schedule. However, favorable clinical responses have been observed in Chinese patients receiving lower doses (≤200 mg/day), prompting further investigation.

Histone deacetylase 8 (HDAC8) plays a role in glioblastoma progression, making it a promising therapeutic target. While HDAC8 inhibitors (HDAC8is) suppress glioblastoma growth and prolong survival in animal models, they do not eliminate HDAC8. In contrast, HDAC8-targeting proteolysis-targeting chimera (PROTAC), a selective HDAC8 degrader, induces proteasomal degradation of HDAC8 and thus eliminates all of its functions.

Immune exclusion is a major barrier to immune checkpoint inhibitor (ICI) efficacy in gastric cancer, yet the spatial mechanisms by which m6A regulators drive this phenotype remain unclear.

This study aimed to develop and evaluate acidic pH- and reactive oxygen species (ROS)-sensitive triblock copolymer nanoparticles, composed of poly(ethylene glycol) (PEG), poly(doxorubicin) (DOX), and hyaluronic acid (HA), for targeted anticancer drug delivery.

Pancreatic cancer (PC) is an aggressive malignancy that has become one of the leading causes of cancer-related death worldwide. Remarkably, phytochemical-based nanoformulations have demonstrated great potential in combating cancer progression. Therefore, the objective of this scoping review is to analyze the most recent advances in the application of nanoformulated phytochemicals against PC.

Ginkgolic acid (GAC), one of the major active constituents of Ginkgo biloba L. (Ginkgoaceae) extract, has been reported as a potential anticancer agent.

Curcumin, a natural compound with broad pharmacological effects, suffers from low bioavailability due to its unstable β-diketone structure. To address this, we designed novel indole-based curcumin analogs via molecular hybridization, replacing the β-diketone with a monocarbonyl bridge to enhance stability. A series of symmetric (1a and 1b) and asymmetric (3a-3i) compounds were synthesized. The antioxidant assays (DPPH method) revealed a concentration-dependent radical scavenging effect, with compound 3e exhibiting 23.1% inhibition at 64 μM. In vitro antitumor screening using the MTT assay across four human cancer cell lines (Eca109, SMMC7721, A549, and MGC803) revealed promising inhibitory effects. Among them, compound 1a displayed the most potent activity against Eca109 cells, with an IC50 value of 6.84 μM, being markedly lower than those of curcumin (29.5 μM) and cisplatin (10.4 μM), indicating superior cytotoxicity. Molecular docking analysis of 1a predicted strong binding to EGFR (-10.9 kcal/mol) and CDK6 (-11.2 kcal/mol), stabilized by hydrogen bonds and hydrophobic interactions. These results validate the novelty of indole modification and correlate in vitro activity with in silico mechanisms.

A series of 1,3,4-oxadiazole-benzimidazole/acetamide derivatives (7a-r) was designed, synthesized, and evaluated for their anticancer activity. NCI-screening results at 10 µM against the 60 human tumor cell line panel revealed a broad-spectrum of antiproliferative effects of the tested compounds. Compounds 7b, 7e, 7f, 7g, 7h, 7k, 7l, and 7r were further tested in a five-dose assay, and they exhibited half-maximal growth inhibitory (GI50) values ranging from 0.90 to 43.50 µM. Focused studies in MDA-MB-231 triple-negative breast cancer (TNBC) cells demonstrated that compounds 7b, 7g, 7h, 7k, and 7l possessed potent antiproliferative activity, with half-maximal inhibitory concentration (IC50) values between 1.92 and 3.69 µM. Mechanistic investigations using cell death pathway inhibitors indicated that compounds 7b, 7k, and 7l did not induce necrosis, apoptosis, or autophagy. Instead, these compounds significantly increased intracellular ferrous iron (Fe2+) and malondialdehyde (MDA) levels and induced lipid peroxidation in MDA-MB-231 cells. In parallel, GPX4 expression was markedly reduced at both the mRNA and protein levels, supporting ferroptosis as the primary mechanism of action. In addition, molecular docking studies and molecular dynamics simulations were performed for derivatives 7b, 7k, and 7l in order to confirm the mechanistic study. Collectively, these findings suggest that the 1,3,4-oxadiazole-benzimidazole/acetamide scaffold represents a promising chemotype for developing ferroptosis-inducing therapeutics targeting TNBC.

The clinical application of doxorubicin (DOX) is severely restricted by its dose-dependent cardiotoxicity. This study aimed to investigate the protective mechanisms of traditional Chinese medicine-derived natural compounds (TCM-NCs) against DOX-induced cardiotoxicity. A systematic analysis was performed on 104 preclinical studies (encompassing in vivo and in vitro models) retrieved from PubMed, Web of Science and Embase, summarising the cardioprotective effects and mechanisms of 65 TCM-NCs. These compounds exert multitarget protective effects by modulating six core pathways: oxidative stress/ferroptosis, apoptosis, inflammation/pyroptosis, mitochondrial homeostasis, autophagy and endoplasmic reticulum stress. Target validation further identified Nrf2, Sirt1, mTOR and AMPK as potential central hub nodes underlying their protective actions. These findings offer a theoretical foundation and promising drug candidates for the prevention of chemotherapy-related cardiac injury, with future research directions focusing on clinical translation and druggability optimisation.