Immune checkpoint inhibitor (ICI)-related pneumonitis (ICI-pneumonitis) is a serious complication, whose clinical course and optimal management strategies remain inadequately elucidated. This study clarified whether post-pneumonitis ICI continuation is safe and feasible, identified risk factors for fatal outcomes or successful continuation, and assessed whether findings from patients with lung cancer can be generalized to those with other malignancies.

The degradation of overexpressed proteins has emerged as a promising strategy for halting disease progression, particularly in cancer. Traditional small-molecule drugs often face limitations in the elimination of pathogenic proteins, leading to the development of targeted protein degradation (TPD) approaches. A prominent strategy for TPD is the proteolysis targeting chimaera (PROTAC) which harnesses the ubiquitin proteasome system, the cell's innate degradation machinery, to degrade proteins of interest (POIs). In this review, we will focus on the design and synthetic strategies that led the advancements of PROTACs as a cancer therapy for the targeted degradation of poly ADP-ribose polymerases (PARPs), glutathione peroxidase 4 (GPX4) and epigenetic regulators. We also aim to address the prevailing challenges in PROTAC development and clinical translation, namely target diversification, oral bioavailability, stability, degradation efficiency, and optimising multivalent binding.

Immune checkpoint inhibitors (ICIs) can induce immune system activation and cause immune-related adverse events (irAEs). This study aimed to assess the incidence and management of irAEs in thymoma patients with preexisting MG who received ICI therapy.

The properties and meridian affinities of Chinese herbal medicine are closely associated with their therapeutic efficacy. This review focuses on approved antitumour Chinese medicines listed in the Pharmacopoeia of the People's Republic of China (2020 Edition, Volume I), highlighting their key components. Statistical methods were used to analyse the properties, flavours and channel tropisms of antitumour traditional Chinese medicine (TCM), including both proprietary formulations and commercially available individual herbs. Distinctive patterns were identified by comparing herb profiles with contemporary experimental studies on antitumour TCM. Analysis revealed that bitter-cold herbs represented the highest proportion of antitumour TCM, with most showing tropism towards the liver channel. These findings provide a reference framework for antitumour drug development, indicating that bitter-cold herbs merit priority as candidate ingredients.

Diabetic macular edema (DME) remains a leading cause of vision loss in the working-age population, yet its management is undergoing a fundamental paradigm shift from high-frequency anti-VEGF monotherapy toward more durable and multi-mechanism therapeutic strategies. This narrative review provides an up-to-date overview of the pharmacological landscape of DME as of 2025, synthesizing evidence from pivotal clinical trials, recent regulatory approvals, and available real-world outcomes. We examine the transition toward injection-sparing approaches and discuss the clinical rationale for targeting alternative biological pathways beyond VEGF inhibition, including angiopoietin-2 (eg, faricimab), the plasma kallikrein-kinin system, and tyrosine kinase-mediated signaling. Collectively, emerging evidence suggests that the future management of DME will be defined by a paradigm shift toward injection-sparing, multi-pathway therapeutic strategies, extending beyond short-term fluid suppression toward a more personalized, precision-medicine framework that prioritizes long-term durability, safety, and functional outcomes.

This retrospective study was to identify the outcomes and safety of anlotinib combined with PD-1 blockades in patients with metastatic esophageal squamous cell carcinoma (ESCC).

Acute myeloid leukemia (AML) remains the most aggressive form of leukemia, underscoring the urgent need for novel treatment strategies. Drug repurposing offers a promising approach to accelerate drug development process. Cardiac glycosides (CGs), traditionally used for heart conditions, have shown potential for AML therapy. As leukemic stem cells (LSCs) are key contributors to AML relapse and chemotherapy resistance, this study aims to elucidate the potential shared mechanisms of proscillaridin (PSN) and ouabain (OUA), two CGs with anti-LSC activity, focusing on their multitarget effects-an emerging strategy in cancer therapy.

Venetoclax (VEN), a selective B-cell lymphoma 2 (BCL-2) inhibitor, is used in pediatric hematologic malignancies. Research on individualized VEN therapy in Chinese pediatric patients remains limited. This study aimed to develop a population pharmacokinetic (PPK) model in Chinese pediatric patients, identify covariates influencing pharmacokinetics, support personalized dosing, and explore exposure-efficacy relationships in pediatric acute myeloid leukemia (AML).

Chemodynamic therapy (CDT) has emerged as a promising cancer treatment strategy leveraging tumor microenvironment conditions to generate reactive oxygen species (ROS) through Fenton-type reactions. This study reports the synthesis, in-depth characterization, and biological evaluation of novel manganese-based zeolitic imidazolate framework (ZIF) nanoparticles, ie, Mn-rods, as a carrier-free potential CDT platform with exceptionally high manganese loading.

Chemotherapy-related toxicity has been associated with body composition, yet there is no consensus on which CT-derived muscle parameter or handgrip strength (HGS) best predicts toxicity in pediatric cancer patients. This study evaluated whether CT-derived body composition parameters and nutritional status independently predict early chemotherapy-related infections and hematologic toxicity in children and adolescents with cancer. In this prospective observational cohort, patients aged 7-18 years undergoing chemotherapy with available CT/PET-CT scans were included. Anthropometric data (weight, height, arm circumference, triceps skinfold thickness) and HGS were collected. At the third lumbar vertebra (L3), skeletal muscle mass (SMM), skeletal muscle index (SMI), total adipose tissue, and muscle radiodensity were measured; psoas area was assessed at L4. Associations were analyzed using χ2 tests and logistic regression adjusted for sex, age, tumor stage, and type. Forty-eight patients were included (mean age 12.6 ± 3.3 years; 64.6% male); 64.6% had hematologic malignancies and 53.6% had advanced disease. Most were classified as having normal nutritional status (50-64.6%). Hematologic (100%) and gastrointestinal (85.4%) toxicities were most frequent. Low SMM and SMI were correlated with a higher risk of infection (OR 4.20; 95% CI 1.23-14.27 and OR 3.92; 95% CI 1.17-13.20, respectively) and fever (OR 4.05; 95% CI 1.21-13.54 and OR 5.82; 95% CI 1.67-20.25, respectively). After adjustment, only low SMI remained independently associated with fever (OR 4.74; 95% CI 1.09-20.61; p = 0.038).

LINKER-MM1 (NCT03761108) is a Phase 1/2 study of linvoseltamab, a human BCMA×CD3 bispecific antibody for patients with relapsed/refractory multiple myeloma (RRMM) who are triple-class exposed (TCE) with ≥ 3 prior lines of therapy (3L+), or triple-class refractory (TCR). To contextualize efficacy data from LINKER-MM1, the Phase 2 linvoseltamab 200 mg cohort (N = 105) was compared with an international external control arm (ECA) comprising 203 patients from participating International Myeloma Working Group sites who met LINKER-MM1 eligibility criteria based on chart reviews. The ECA reflected real-world standard-of-care (RW SOC). An independent data review committee assessed data relevance, quality, and cohort comparability, while a separate independent central review committee evaluated response data. Inverse probability of treatment weighting was used to balance baseline characteristics between the linvoseltamab arm and the ECA. Linvoseltamab had a higher objective response rate (weighted odds ratio 3.0 [95% confidence interval (CI): 1.9-4.1]) and longer median progression-free survival (weighted hazard ratio [wHR] 0.33 [95% CI: 0.28-0.40]), time to next treatment (wHR 0.34 [95% CI: 0.29-0.44]), and overall survival (wHR 0.72 [95% CI: 0.58-0.98]) than RW SOC. These findings highlight linvoseltamab's potential as an effective treatment for 3L+ and TCE/TCR RRMM.

In this study, we investigated the anticancer activity of cedrol, a sesquiterpene alcohol, in the human epidermoid carcinoma cell A431 and in epidermal carcinoma 3D skin. Although various physiological activities of cedrol have been reported, the anticancer effect of cedrol in epidermal carcinoma and its molecular mechanisms still remain unclear. Cedrol exhibited significant cytotoxicity in A431 cells in a concentration-dependent manner and reduced the expression of minichromosome maintenance (MCM) proteins. To elucidate the underlying anticancer mechanisms, cell cycle and apoptosis analyses were performed. Cedrol induced dose-dependent G0/G1 phase arrest in A431 cells after 24 h of treatment, accompanied by induction of p53 and p21 and reduction of cyclin E and CDK2. After 48 h of cedrol treatment, apoptosis was observed, as demonstrated by the increase in SubG1 population and Annexin V-positive apoptotic cells using flow cytometry. Cedrol-induced apoptosis was further confirmed by increased expression of the death receptor Fas and the pro-apoptotic protein Bax, decreased expression of the anti-apoptotic protein Bcl-2, release of cytochrome c, and PARP cleavage following caspase activation, indicating apoptosis occurred via both intrinsic and extrinsic pathways. In addition, the cytotoxic effect of cedrol was also observed in an epidermal carcinoma 3D skin constructed using A431 cells, but not in a normal 3D skin constructed using HaCaT cells. Taken together, these findings suggest that cedrol may serve as a novel anticancer therapeutic candidate for epidermal carcinoma and propose that the epidermal carcinoma 3D skin model can be utilized in nonclinical trials.

Poly(ADP-ribose) polymerase (PARP) inhibition (PARPi) is a precision medicine strategy in advanced prostate cancer, with the greatest benefit seen in a subset of patients with homologous recombination repair (HRR) gene alterations. Combination approaches may expand activity beyond HRR-altered disease. We conducted a phase 2 study of the PARP inhibitor olaparib in combination with the anti-PD-L1 antibody durvalumab in an HRR-unselected population of men with metastatic castration-resistant prostate cancer (mCRPC).

Poly-ADP ribose polymerase inhibitors (PARPi) are well-known to treat tumors that are deficient in homologous recombination (HR) DNA repair. However, PARPi can treat breast cancer gene (BRCA) wild-type tumors, the mechanisms behind which are not fully elucidated. We previously reported that tumor-intrinsic programmed death ligand-1 (PD-L1) signals promote HR, and that genetic tumor PD-L1KO impairs HR and sensitizes tumors to PARPi. Despite significant PARPi efficacy in PD-L1KO tumors, US Food and Drug Administration (FDA)-approved anti-PD-L1 antibodies did not improve PARPi. Thus, additional clinically translatable approaches to target tumor-intrinsic PD-L1 signals to elicit PARPi sensitivity are needed.

Standard adjuvant chemotherapy for stage III colon cancer consists of a fluoropyrimidine-plus-oxaliplatin regimen. Whether the addition of atezolizumab (an anti-programmed death ligand 1 agent) to a modified FOLFOX6 regimen (fluorouracil, oxaliplatin, and leucovorin; called mFOLFOX6) would improve outcomes in patients with stage III colon cancer with mismatch repair-deficient (dMMR) status is unclear.

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.

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.

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.