Molecular characterization has become essential for the diagnosis and treatment of pediatric brainstem lesions. While frame-based stereotactic and robotic-assisted biopsies are well established, comparative data on frameless VarioGuide biopsy for pediatric brainstem lesions remain scarce. This study evaluated the diagnostic performance, safety, and workflow characteristics of frameless VarioGuide biopsy compared with frame-based stereotactic and ROSA-assisted techniques.

We retrospectively reviewed all pediatric patients (≤ 18 years) who underwent stereotactic biopsy of a brainstem lesion at a single tertiary neurosurgical center between 2016 and 2026. Patients were grouped according to biopsy technique (frameless VarioGuide, frame-based stereotaxy, or ROSA-assisted biopsy). Diagnostic yield, molecular diagnostic yield, complications, operative times, and workflow parameters were analyzed.

Twenty-two pediatric patients met inclusion criteria. Six underwent frameless VarioGuide biopsy, nine frame-based stereotactic biopsy, and seven ROSA-assisted biopsy. Overall diagnostic and molecular diagnostic yields were 95%. Diagnostic and molecular diagnostic yields were 100% with VarioGuide, 89% with frame-based stereotactic biopsy, and 100% with ROSA-assisted biopsy, without statistically significant differences between groups (p = 0.62). Median operative times were similar among groups (32, 36, and 25 min, respectively; p = 0.28). However, preoperative setup time differed significantly, with the shortest duration observed in the VarioGuide cohort (40.5 min) compared with ROSA-assisted biopsy (64 min) and frame-based stereotaxy (112 min; p = 0.002). Despite the absence of intraoperative neuropathological assessment, all VarioGuide procedures yielded diagnostically and molecular-pathologically informative tissue. No procedure-related hemorrhage, infection, permanent neurological deficit, or procedure-related mortality were observed.

In this exploratory single-center cohort, frameless VarioGuide biopsy achieved high diagnostic and molecular diagnostic yields without permanent procedure-related morbidity and was associated with shorter preoperative setup time. These findings support further evaluation of frameless VarioGuide biopsy as a workflow-efficient approach for tissue acquisition in pediatric brainstem lesions.

Biomarkers used to guide immunotherapy in non-small cell lung cancer (NSCLC) are invasive, variably available, and insufficient to capture clinical and regional heterogeneity, leaving many patients inadequately stratified for prognosis. We develop a clinical attribute-based framework that leverages routinely collected variables to estimate survival risk, even when baseline data are incomplete. We analyze 17 051 patients with NSCLC treated with immunotherapy, assembled from published cohorts and tertiary centers across multiple regions, and evaluate seventeen common clinical attributes using a two-stage survival modeling strategy with external validation in Western and East Asian populations. Clinical attributes exhibit context-dependent prognostic effects across variable-defined strata and survival endpoints, with performance status and disease stage emerging as the most consistent determinants of survival risk prediction, alongside region-specific modifiers. Here we show that this "start-anywhere" clinical risk matrix provides robust, population-aware prognostic stratification and complements biomarkers for assessing immunotherapy outcomes in patients with NSCLC.

As an anti-HER2 antibody-drug conjugate, SHR-A1811 has exhibited significant antitumor activity in patients with HER2-low advanced breast cancer. This trial aims to explore the efficacy and safety profile of SHR-A1811 as a neoadjuvant therapy for hormone receptor-positive, HER2-low (HR + /HER2-low) breast cancer. We conducted a single-arm, phase 2 study enrolling women aged 18 to 70 years with untreated HR + /HER2-low invasive breast cancer (cT2-3, cN0-3) and a Ki-67 proliferation index exceeding 14%. Eligible patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and received intravenous SHR-A1811 at a dose of 6.4 mg/kg every three weeks for eight cycles. The primary endpoint was the objective response rate, assessed in all patients who received at least one treatment cycle. Secondary endpoints included pathological complete response (pCR, residual cancer burden (RCB) 0-1 rate, event-free survival (EFS), disease-free survival (DFS), and distant disease-free survival (DDFS). In total, 66 of 101 screened patients (65.3%) were enrolled, with 65 included in the efficacy analysis and 66 in safety analysis. The objective response rate was 81·5% (95% confidence interval (CI), 70·0-90·1), exceeding the protocol-specified threshold of 66·0%. Pathological complete response (ypT0/Tis ypN0) was observed in 2 patients (3.1%; 95% CI, 0.4-10.8), while 6 patients (9.2%; 95% CI, 3.5-19.6) achieved a residual cancer burden class 0-1. Treatment-related grade ≥3 adverse events occurred in 37.9% of patients. The most common grade ≥3 adverse events were neutropenia (27.3%), leukopenia (16.7%), and anemia (13.6%). No treatment-related deaths or interstitial lung disease were reported. In summary, SHR-A1811 monotherapy achieved favorable response rates with manageable toxicity, suggesting a potential alternative neoadjuvant option for HR + /HER2-low breast cancer. Further randomized trials may be necessary to assess its clinical value more comprehensively. Follow-up continues for survival. ClinicalTrials.gov identifier: NCT05911958.

KRAS G12C (Gly¹²→Cys) inhibitors (G12Cis) have improved outcomes for patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC), but their clinical benefit is limited by the emergence of resistance mechanisms. Here, we demonstrate that combining the RAF/MEK clamp avutometinib and the focal adhesion kinase (FAK) inhibitor defactinib with a G12Ci enhanced antitumor activity by deepening mitogen-activated protein kinase (MAPK) pathway suppression and simultaneously inhibiting adaptive resistance pathways induced by G12Ci and avutometinib treatment, including FAK and PI3K signaling. In KRAS G12C NSCLC mouse models, the triplet combination produced greater tumor growth inhibition than either sotorasib alone or the sotorasib plus avutometinib doublet. Moreover, in KRAS G12C NSCLC mouse models resistant to sotorasib, the addition of avutometinib and FAK inhibition restored sensitivity to sotorasib and increased both the depth and durability of antitumor responses. Collectively, these findings demonstrate that concurrent targeting of KRAS G12C, RAF/MEK, and FAK signaling can overcome multiple resistance mechanisms and provide a strong rationale for the clinical evaluation of sotorasib, avutometinib, and defactinib in patients with KRAS G12C-mutated NSCLC (RAMP 203; NCT05074810).

Due to the substantial impact of brain tumors on human health, precise identification of tumor types is vital for patient prognosis and guiding treatment decisions. Magnetic Resonance Imaging (MRI) technology, owing to its non-invasive nature and high resolution, is indispensable in accurately classifying brain tumor types. However, manual interpretation of MRI images is not only time-consuming and labor-intensive but also susceptible to subjective bias. Hence, many automatic brain tumor diagnosis systems utilizing deep learning techniques have been developed. This paper introduces an advanced modularized Convolutional Neural Network (CNN) that incorporates ConvDAtt block, Complementary Information (CI) downsampling block, and Spatial Pyramid Pooling (SPP) block. Firstly, the ConvDAtt block combines convolution, depth-separable convolution and Coordinated Attention (CA) mechanism. The module alleviates the gradient vanishing problem in deep neural network training, enhancing the training stability and performance of the model. In the ConvDAtt block, the CA mechanism can not only capture information across channels, but also sense direction and position sensitive information, improving the accuracy of the model's identification of objects of interest. Secondly, the CI block is a downsampling block with convolution and pooling functions. In the CI block, there is a complementary relationship between the pooling layer and the convolution layer, which is mainly reflected in two aspects, feature extraction and dimensionality reduction, enlargement of receptive field. Moreover, the complementary relationship can solve the problem of information loss in the process of downsampling, while also significantly reducing computational cost. Thirdly, the SPP block extracts features from different scales of the input data and integrates these features, thus enhancing the performance of the network, and enhancing the robustness of the model. The combination of ConvDAtt block, CI block and SPP block can effectively extract the information features and discriminant features of brain tumor MRI images, which has the advantages of parameter reduction, stable training and clear structure.

Pancreatic cancer has a dismal prognosis and limited therapeutic options, highlighting an urgent need for effective treatments. Sophoricoside (SOP), a natural isoflavone glycoside, has exhibited anticancer activities in multiple malignancies, including lung cancer, glioblastoma, and hepatocellular carcinoma. We combined cellular assays, network pharmacology, machine learning, and multi-omics to investigate SOP's effects. SOP-inhibited proliferation of MIA PaCa-2, SW1990, and PANC-1 cells dose-dependently. Network pharmacology revealed 85 overlapping targets enriched in MAPK, apoptosis, and PD-L1/PD-1 pathways. Machine learning and differential expression identified PTPN1 as the core target. PTPN1 was markedly upregulated in pancreatic adenocarcinoma, and its high expression correlated with poor survival and immune infiltration. Functional enrichment linked PTPN1 to TGF-β, VEGF, and metabolic reprogramming. Molecular docking suggested a possible binding mode between SOP and PTPN1, involving four predicted hydrogen bonds. SOP reduced PTPN1 mRNA, and PTPN1 knockdown phenocopied SOP's antiproliferative effect with no additivity upon combination. Collectively, this first report demonstrates that SOP restrains pancreatic cancer cell proliferation, with PTPN1 identified as a key functionally required downstream mediator based on integrative computational and functional evidence. This work offers an integrated strategy for mechanistic exploration and highlights PTPN1 as a promising therapeutic biomarker and target for pancreatic cancer.

Fifteen new actinomycin analogs were obtained from the marine-derived Streptomyces polyantibioticus S4D258. Structural elucidation of these compounds was successfully achieved by comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HR-ESIMS), nuclear magnetic resonance spectroscopy (NMR), and Marfey's method. Notably, actinomycins H₁-H₅ (1-5) contain L-serine (L-Ser), D-2-aminobutyric acid (D-2-Aba), and L-2-methylaminobutyric acid (L-2-MeAba) residues, whereas actinomycin H₆ (6) comprises a 5H-oxazolo[4,5-b]phenoxazine chromophore. Actinomycins H₇-H₁₅ (7-15) are nine truncated actinomycin analogs only containing one pentapeptidolactone unit. Actinomycins H₁ (1) and H₉ (9) exhibited inhibitory activities against the proliferation of triple-negative breast cancer MDA-MB-231 cells with IC50 values of 28.00 nM and 4.34 µM, respectively. Mechanistic investigation revealed that the above two actinomycin analogs not only induce S-phase arrest, mitochondrial membrane potential depolarization, and apoptosis, but also trigger ferroptosis, as revealed by an increase in the level of reactive oxygen species, lipid peroxidation, and malondialdehyde. Collectively, our findings enriched the structural diversity of natural actinomycins and inspired the re-examination of actinomycin analogs as anticancer leads against triple-negative breast cancer.

Flow cytometry is the cornerstone for establishing the diagnosis of chronic lymphocytic leukemia (CLL), owing to its characteristic and well-defined immunophenotype that enables accurate distinction from other leukemias and lymphomas. Beyond diagnosis, flow cytometry provides essential prognostic information and allows sensitive detection of minimal residual disease (MRD), a strong predictor of clinical outcome. CLL MRD assessment is increasingly used to guide risk stratification, therapeutic decision-making, and treatment duration in the era of targeted therapies and immunotherapies. This chapter reviews best practices for specimen collection, processing, staining, and data analysis and summarizes the principles of flow cytometric MRD assessment in CLL.

Metastatic colorectal cancer (mCRC) is a leading cause of cancer-related mortality worldwide. FOLFOXIRI combined with targeted agents has shown promising outcomes in mCRC. This meta-analysis compares efficacy and safety of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab in patients with mCRC.

A literature search was conducted across PubMed, Cochrane, Embase, Scopus, and clinicaltrials.gov until February 2025. Analysis was performed using RStudio v4.5.0. Pooled estimates are reported as hazard ratios, odds ratios, risk ratios, and mean difference with 95% CIs using random-effects model. Heterogeneity was assessed using I² statistics.

Four studies (3 RCTs, 1 observational) comprising 561 patients were included. Overall survival did not differ significantly between FOLFOXIRI-cetuximab and FOLFOXIRI-bevacizumab (HR: 1.22; 95% CI: 0.78 - 1.90; p = 0.386). Progression-free survival also did not differ significantly (HR: 1.32; 95% CI: 0.76-2.31; p = 0.324). Objective response rate, complete response, and partial response did not differ significantly [(OR: 1.48; 95% CI: 0.50-4.37; p = 0.4772), (OR: 1.59; 95% CI: 0.66-3.86; p = 0.303), and (OR: 1.60; 95% CI: 0.52-4.93, p = 0.414) respectively]. Depth of response showed no significant difference (MD: 15.29; 95% CI: -1.35-31.94; p = 0.07). Hypomagnesemia and acneiform rash were significantly more frequent with cetuximab (p < 0.01). However, alopecia, anemia, neurotoxicity, and all-grade stomatitis showed no difference between the two arms.

FOLFOXIRI-cetuximab did not improve PFS, OS, or response rates in patients with mCRC compared with the bevacizumab combination; however, it was associated with significantly higher rates of hypomagnesemia and acneiform rash.

Poor penetration into tumor tissue remains a major barrier to effective nanomedicine delivery, particularly in glioblastoma multiforme (GBM). Here, nanoparticle transport was computationally studied to rationally design an ultrasmall chemotactic nanomotor that improves penetration into dense tumor tissue. The nanomotor comprises a targeting human heavy-chain ferritin (HFn) nanocage and a catalytic cerium oxide (CeO₂) component. Leveraging transferrin receptor‑1 overexpression on brain microvascular endothelial cells and GBM cells, HFn enables transport across an in vitro blood-brain barrier (BBB) model and accumulation in GBM spheroids. The CeO₂ domain catalyzes hydrogen peroxide decomposition in the tumor‑mimicking microenvironment, generating oxygen and imparting directional propulsion along H₂O₂ gradients. In chemotaxis assays, the nanomotors actively migrated toward localized H₂O₂ sources and GBM cells embedded in Matrigel. In large U87 spheroids (>400 µm), HFn@CeO₂ nanomotors penetrated deeply and distributed throughout the spheroid core, whereas non‑propelled HFn nanocarriers remained confined mainly to the periphery. Doxorubicin‑loaded nanomotors (HFn@CeO_2-DOX) achieved substantially enhanced intratumoral DOX distribution and reduced IC₅₀ (0.33 µM) compared with HFn-DOX (1.13 µM) and free DOX (1.75 µM) in GBM spheroids. These results provide a promising basis for future in vivo evaluation in brain tumor therapy.