Photothermal nanomaterials enable precise tumor ablation but face limitations in biodistribution, tissue penetration, toxicity, and biodegradability. Here, we present a unique concept for nanoparticle-free photothermal therapy based on the lysosomal entrapment of cationic amphiphilic small molecular dyes for spatially controlled vapor bubble (VB)-mediated tumor cell ablation. This strategy, which exploits a universal biological and physical effect, uses intracellular pH gradients for extensive local dye enrichment in acidified organelles, transforming them into transient endogenous nanosized photothermal reactors for subsequent light activation. Using sunitinib, a clinically approved lysosomotropic anticancer drug, and the commercially available dye LysoTracker Deep Red, lacking intrinsic anticancer activity, we demonstrate pulsed laser-induced VB formation from dye-enriched lysosomal compartments, leading to selective photomechanical disruption of various ex vivo cancer cell models across two-dimensional (2D) cultures, 3D spheroids, patient-derived neuroblastoma tumoroids, and tumor fragments from a patient with ovarian carcinoma. This approach allows precise, low-fluence, and wavelength-tunable cancer tissue ablation without the need for synthetic photoresponsive nanoparticles.

Male breast cancer (MBC) is rare and remains largely managed using knowledge derived from female breast cancer. Here, we generated a multiplatform single-cell and spatial transcriptomic atlas integrating scRNA-seq, SeekSpace, Visium HD, Xenium In Situ, and multiplex immunohistochemistry data from male and female breast cancer cohorts, covering more than 660,000 cells. We identified male-specific tumor cells (MSTCs) that were enriched in MBC, rare in female breast cancer, and associated with poorer disease-free survival. MSTCs exhibited neural transcriptional programs, increased transcriptome-inferred copy number variation burden, and spatial coupling with fatty acid metabolism signals. MSTC-enriched regions showed reduced antigen-presentation signatures and spatial association with APOE⁺/CD163⁺ macrophages, with GRN-SORT1 emerging as a candidate macrophage-tumor interaction axis. These findings define an MBC-associated malignant state and its immune-metabolic spatial context.

The fecal lipidomic changes underlying the colorectal adenoma-carcinoma sequence remain incompletely characterized, particularly regarding the continuous metabolic trajectory and heterogeneity of precancerous adenomas. We aimed to use publicly available multi-omics data and an integrative computational framework to identify candidate lipidomic features associated with a CRC-like metabolic state in adenomas.

We developed an extreme-phenotype machine learning strategy using fecal lipidomics from healthy controls and colorectal cancer (CRC) patients (Study ID: ST003798) to build a diagnostic model, which was then blindly applied to adenoma patients to compute a Fecal Lipidomic Malignancy Risk Score (FL-MRS), interpreted here as a CRC-like lipidomic similarity score. SHAP analysis prioritized influential lipid features, and cross-sectional pseudotime trajectory inference reconstructed the metabolic continuum. Transcriptomic data from TCGA-COAD and single-cell RNA-seq (Broad Institute) were integrated to explore potential tissue-level correlates. Targeted single-molecule trend verification of the top lipid candidate was performed in an independent cohort (ST002787), as full model replication was not feasible due to limited inter-cohort feature overlap. Multiple sensitivity analyses were conducted to assess the robustness of the computational pipeline.

The Random Forest model showed robust performance on the independent test set (AUC = 0.864). When applied to adenomas, 51.7% of patients exceeded the FL-MRS threshold derived from extreme phenotypes; however, this proportion far exceeds the known clinical adenoma-carcinoma progression rate (approximately 5-10%), indicating that FL-MRS should be interpreted as a metabolic similarity metric rather than a direct cancer risk probability. SHAP analysis prioritized arachidonic acid-derived cholesterol ester CE(20:4) as the top predictive feature, with 100% bootstrap selection frequency. Integrative analysis of independent transcriptomic datasets identified upregulation of PTGS2 (COX-2) in tumor tissue and its predominant expression in stromal cells. External single-molecule targeted verification confirmed an accumulation trend of CE(20:4) and an early adenoma-phase peak of eicosanoid mediators (including oxidative stress and LOX-pathway metabolites). Notably, CE(20:4) levels did not differ significantly between adenoma and CRC (P = 0.055), consistent with its proposed role as an early event marker. Pseudotime trajectory inference was insensitive to root node assignment.

This computational study suggests that fecal CE(20:4) and the associated COX-2 pathway may represent candidate features of a CRC-like metabolic state in colorectal adenomas. FL-MRS is not proposed as a clinical diagnostic or risk-prediction tool; rather, it serves as a research instrument for quantifying CRC-like metabolic similarity and guiding future validation studies. All findings are derived from publicly available retrospective data without independent experimental validation and should be regarded as hypothesis-generating. The complete analysis code is publicly archived to ensure reproducibility and facilitate future validation.

Growing evidence links the gut microbiome to colorectal cancer (CRC) progression, with certain bacterial species enriched in specific molecular tumor subtypes. DNA mismatch repair deficiency in CRC, evidenced by the presence of microsatellite instability (MSI), has been consistently associated with a favorable prognosis, and may be related to certain aspects of the microbiome. Here, we examined the relationship between tumor microbial biodiversity and MSI status.

Diagnostic tumor tissue samples were obtained from the Seattle site of the Colon Cancer Family Registry (SCCFR) and a companion study; both recruited patients diagnosed with incident CRC from 1998 to 2007. MSI status assessment and prokaryotic 16S rRNA gene sequencing was performed on the tumor tissue samples. We used an adaptive test of alpha-diversity (aMiAD) to estimate the association between microbial biodiversity and MSI status. We performed differential abundance analysis with ANCOM-BC to identify enriched genera in tumor tissue, based on dichotomized MSI status. Analyses were adjusted for age, sex, smoking history, and tumor location (N = 632).

The adaptive aMiAD effect estimate was -1.08 (p = 0.29), suggesting that MSI-high tumors had lower estimated alpha-diversity, though this difference was not statistically significant. We identified 20 differentially abundant genera in CRC tumors according to MSI status, with 8 enriched genera and 12 depleted genera in MSI-high tumors. The most strongly enriched genera in MSI-high tumors were Gemella and Lawsonella, while Sporolactobacillaceae and Cloacibacterium were the most strongly depleted. Fusobacterium was enriched in MSI-high tumors only after subsetting the genus to Fusobacterium nucleatum specific sequences.

We did not detect a statistically significant association between the adaptive alpha-diversity measure and MSI status, though individual measures concordantly estimated a depletion of alpha-diversity in the MSI-high tumors. We found evidence of differential abundance of certain genera dependent on MSI status, including several novel associations.

Posterior fossa syndrome (PFS) is a common complication following surgical resection of paediatric posterior fossa tumours, characterised by mutism, ataxia, emotional disturbance, and cognitive impairment. Despite significant rehabilitation needs, there is limited evidence regarding effective therapeutic approaches, including the role of music therapy. Music therapy is uniquely positioned to address the multidimensional needs of children with PFS, yet the low incidence and clinical heterogeneity of the syndrome preclude traditional empirical research designs. International consensus guidelines are therefore needed to consolidate clinical knowledge and support consistent, high-quality practice. This protocol describes a two-phase study to develop international consensus guidelines for music therapy practice with children with PFS. Phase 1 involves a pre-Delphi consultation with three regional Advisory Panels (North America, Europe, Australia), each comprising family representatives, music therapists, allied health professionals, and medical practitioners. These panels will identify clinical priorities, family concerns, and interdisciplinary outcomes to inform the development of the survey instrument. Phase 2 uses an international Delphi process with a minimum of 30 experienced paediatric music therapists, proceeding through three to five iterative rounds of item generation, rating, and refinement. Consensus is defined a priori as ≥80% agreement. Quantitative analysis will be conducted in R; qualitative data will be analysed thematically. The study will be conducted and reported in line with DELPHISTAR recommendations. The resulting consensus guidelines will support developmentally responsive, family-centred music therapy assessment and intervention for children with PFS, while identifying priority areas for future research in paediatric neuro-oncology and neurorehabilitation.

Pancreatic functioning neuroendocrine neoplasms (PanNENs) are rare and characterized by variable and heterogeneous clinical manifestations, comprising both symptoms and signs of tumor growth and systemic manifestations of hormonal hypersecretion. The diagnosis is challenging due to their rarity, neoplasm localization and diverse secretory profile. A subset of these neoplasms may develop in the context of inherited syndromes and harbor specific genetic alterations requiring genetic counseling of other family members. These particular features make the management of patients with a functioning PanNEN syndrome requiring a multidisciplinary approach. Surgical resection of local disease, antisecretory medical treatment, locoregional treatment and systemic treatments are employed on an individualized basis. The treatment landscape of advanced NENs progressing after systemic treatment or after exhibiting intolerance to sequential lines of treatment is rapidly evolving supporting the introduction of additional therapies with promising results.

Zolbetuximab plus platinum-fluoropyrimidine chemotherapy has emerged as an approved first-line treatment option for patients with CLDN18.2-positive, HER2-negative gastric or gastroesophageal junction adenocarcinoma. However, its implementation in routine practice is frequently challenged by early gastrointestinal toxicities, particularly nausea and vomiting during the first infusion. A clinically important observation from the combined Japanese subgroup analysis of the phase III SPOTLIGHT and GLOW trials is that Japanese patients achieved a greater progression-free survival benefit (median 20.53 months; hazard ratio [HR] 0.482) than the overall trial populations (HR 0.69-0.75), alongside higher relative dose intensity (> 80% in 98.2% versus 88.9% of non-Japanese patients) and greater cumulative drug exposure. Notably, no Japanese patient discontinued zolbetuximab permanently due to nausea or vomiting. These observations are hypothesis-generating and suggest that systematic, proactive toxicity management and maintained drug delivery may contribute to clinical benefit, while alternative biological, clinical, and population-level explanations should also be considered. Accumulating real-world evidence suggests that zolbetuximab-related adverse events should not be viewed in isolation. Endoscopy-based data have shown early-onset gastritis in 89.7% of evaluated patients, with diffuse gastritis associated with more frequent anorexia and greater serum albumin decline. Pragmatic institutional protocols, real-world safety frameworks, and Delphi-based consensus guidance indicate that high-emetic-risk antiemetic prophylaxis, stepwise infusion-rate escalation, temporary interruption, rescue antiemetics, intravenous hydration, and education of patients and clinic staff can improve tolerability and reduce treatment interruption in subsequent cycles. Formal pharmacokinetic analyses further demonstrate an association between higher average zolbetuximab concentration throughout treatment (Cave) and longer progression-free and overall survival. These findings provide a plausible mechanistic link between dose delivery and clinical benefit, but they do not by themselves establish causality. This review proposes an integrated clinical framework in which nausea, vomiting, gastritis, anorexia, and hypoalbuminemia are understood as potentially interconnected on-target/off-tumor gastric toxicities requiring multidisciplinary management by physicians, nurses, and pharmacists. Throughout the review, we distinguish established evidence from hypotheses generated by clinical, endoscopic, real-world, and pharmacokinetic observations. Proactive toxicity management may preserve treatment continuity and effective drug exposure, thereby maximizing the likelihood of clinical benefit; however, prospective studies are required to determine whether supportive-care interventions directly improve efficacy outcomes.

This study aims to investigate whether Methyl-Transferase-Like Protein 16 (METTL16) promotes colorectal cancer (CRC) progression through regulating branched-chain amino acid (BCAA) transaminase 1 (BCAT1)-mediated metabolism to modulate CD8⁺T cell-mediated anti-tumor immunity. METTL16 levels were measured in clinical CRC samples and cell models using IHC, qPCR and western blot. Functional assays (CCK-8, EdU, wound healing, transwell) were performed to evaluate the impact of METTL16 knockdown on CRC cell behaviors. A co-culture system with CD8⁺T cells was established to assess immune evasion mechanisms. RIP, MeRIP, and mRNA stability assays were conducted to explore METTL16's regulation of BCAT1 via m6A modification. Metabolomics analysis using LC-MS/MS quantified branched-chain amino acids (BCAAs). In vivo experiments utilized a xenograft mouse model to validate findings. METTL16 was elevated in CRC. Knockdown of METTL16 suppressed malignant phenotype of CRC cell, while enhancing CD8⁺T cell proliferation and cytotoxic molecule secretion (IFN-γ, IL-2, and GzmB). METTL16 regulated BCAT1 expression through m6A-dependent mRNA stabilization, promoting BCAAs metabolism. Rescue experiments demonstrated that BCAT1 overexpression reversed the regulation of METTL16 knockdown on tumor cell malignancy and CD8⁺ T cell responses. In vivo, METTL16 depletion inhibited tumor growth, reduced Ki-67 expression, and enhanced CD8⁺T cell infiltration and effector molecule levels. METTL16 drives CRC progression by promoting BCAT1-mediated BCAAs metabolism and facilitating immune evasion through suppression of CD8⁺T cell function.

Evasion of ferroptosis has been increasingly recognized as an important mechanism underlying lenvatinib resistance in hepatocellular carcinoma (HCC). However, the roles of deubiquitinating enzymes in ferroptosis regulation and the post-translational control of key ferroptosis regulators in HCC remain poorly understood.

Public lenvatinib resistance-related and ferroptosis-related datasets were analyzed to identify candidate deubiquitinating enzymes associated with HCC therapeutic resistance and ferroptotic stress. Loss- and gain-of-function assays were performed to evaluate the effects of OTUD1 on lenvatinib sensitivity, erastin-induced ferroptosis, and HCC cell growth. Subcutaneous xenograft and orthotopic tumor models were used to assess the role of OTUD1 in tumor growth and ferroptosis resistance in vivo. Western blotting, RT-qPCR, co-immunoprecipitation, cycloheximide chase, MG132 rescue, ubiquitination, SLC7A11 rescue, and ERK1/2 pathway modulation assays were conducted to investigate the underlying mechanism. Clinical HCC specimens and public datasets were analyzed to determine OTUD1 expression and its association with patient prognosis.

OTUD1 was identified as a gene associated with lenvatinib resistance in HCC. Knockdown of OTUD1 sensitized HCC cells to lenvatinib, and this effect was abolished by ferroptosis inhibition. OTUD1 knockdown enhanced ferroptosis in HCC cells, whereas OTUD1 overexpression suppressed it. Moreover, OTUD1 promoted HCC growth and conferred ferroptosis resistance in mice. Mechanistically, OTUD1 interacted with solute carrier family 7 member 11 (SLC7A11) and removed its K48-linked polyubiquitin chains, thereby stabilizing SLC7A11 protein levels. In addition, ERK1/2-dependent phosphorylation of OTUD1 at Ser216 strengthened its interaction with SLC7A11, further enhancing SLC7A11 stability and promoting ferroptosis resistance. Analysis of clinical samples and public datasets further revealed that OTUD1 was upregulated in HCC tissues and correlated with poor prognosis.

Our findings identify the ERK1/2-OTUD1-SLC7A11 axis as a key mechanism mediating ferroptosis resistance in HCC. These results suggest that OTUD1 may serve as a potential therapeutic target for HCC.

Chemoresistance remains a major concern in combating cancer. Colorectal cancer progression is associated with augmented TGF-β serum level. The role of TGF-β2 in promoting doxorubicin resistance in Colo205 cell line was investigated by treating with dox ± TGF-β2 for 7-days. Cell viability, proliferation, cytotoxicity, rhodamine123 efflux, MDR1 expression at gene, surface, and total protein levels, apoptosis assay, induction of autophagy by acridine orange, monodansyl cadaverine staining, and LC3II/I protein ratio were examined. Expression of epithelial, mesenchymal, stem cell markers, regulation of Dab2 and HMGB1 (high mobility group box 1), activation of NF-κB (p65) were also evaluated. Cell proliferation was inhibited after day 1; while loss of viability and cytotoxicity occurred after day 3, with no comparable loss after 7 days. MDR1 protein and gene levels were significantly increased after day 1 in co-treated group alone while elevation in all treatments was noted after 3 and 7 days. Induction of autophagy, increased mesenchymal and stem cell markers, and downregulation of Dab2 protein was observed after 7 days. In TGF-β2 groups, HMGB1 level was significantly decreased, and arrest of NF-κB nuclear translocation was noted. Thus, the presence of TGF-β2 ligand might determine the dox resistance pathway in metastatic colon cancer cell line, Colo205 with smad4 mutation.