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Scaffold-free 3D-cell co-culture model system for the study of metastatic cancer in the brain TME.

Cancer involves complex and dynamic interactions among tumor, stromal, immune cells, and the surrounding matrix, however, the protected micr … vant tool for studying cancer-endothelial crosstalk and key biological processes that unfold in the tumor microenvironment, to ultimately improve diagnostic capabilities and patient outcomes.

Understanding tumor adaptations and resistance to MET inhibitors in MET-altered non-small cell lung cancer.

AIM: Type Ib MET inhibitors are clinically active in selected MET-altered non-small cell lung cancer, particularly tumors with MET exon 14 skipping or MET amplification, but acquired resistance remains incompletely understood. Here, we investigated resistance across biologically distinct MET-altered contexts, including MET exon 14 skipping, MET amplification, and MET overexpression. METHODS: Paired baseline and progression samples from seven patients treated with tepotinib or capmatinib were analyzed using spatial transcriptomics, whole-exome sequencing, RNA sequencing, CRISPR screening, and

A multi-omic machine learning approach deconstructs the role of amino acid metabolism in the immune microenvironment and prognosis of colon adenocarcinoma.

BACKGROUND: The clinical heterogeneity of colon adenocarcinoma (COAD) complicates patient prognosis and treatment. While metabolic reprogramming is a key driver of tumor progression, the role of histidine metabolism in the COAD immune microenvironment remains unclear. METHODS: Through an integrated analysis of public single-cell and bulk transcriptomic data, we mapped the COAD cellular atlas and assessed histidine metabolism activity. A prognostic Histidine Metabolism-related Model (HRM) was constructed using an ensemble of 101 machine learning algorithms, and its biological underpinnings wer

Evaluation of NANOG/HDAC1 Expression in Predicting Outcomes of BCG Therapy in Non-Muscle Invasive Bladder Cancer.

Urinary bladder cancer includes non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). While patients with NM … ggested to directly increases HDAC1 expression, which could suppress lymphocyte infiltration in the tumor microenvironment by altering immune-related gene expression. These findings suggest that the NANOG/HDAC1 axis plays a key role in predicting resistance to intravesical BCG therapy in NMIBC.

Toyaburgine, a Synthetic N-Biphenyl-Dihydroisoquinoline Inspired by Related N,C-Coupled Naphthylisoquinoline Alkaloids, with High In Vivo Efficacy in Preclinical Pancreatic Cancer Models.

Pancreatic cancer is a highly aggressive and lethal malignancy, with a 5-year survival rate below 10%. Traditional chemotherapy, including gemcitabine, has limited efficacy due to chemoresistance and a unique tumor microenvironment characterized by hypovascularity and nutrient deprivation. This study reports on the discovery of a new N-biphenyl-dihydroisoquinoline, named toyaburgine (4), inspired by naturally occurring N,C-coupled naphthylisoquinoline alkaloids. Developed through systematic structural optimization, toyaburgine is a potent anticancer agent, showing promise for pancreatic cancer…

Integrated multiomics revealed adenosine signaling predict immunotherapy response and regulate tumor ecosystem of melanoma.

Extracellular adenosine is extensively involved in regulating the tumor microenvironment. Given the disappointing results of adenosine-targeted therapy trials, personalized treatment might be necessary, tailored to the microenvironment status of individual patients. Here, we introduce the adenosine signaling score (ADO-score) model using non-negative matrix fraction identified patient subtypes using publicly available melanoma dataset, which aimed to profile adenosine signaling-related genes and construct a model to predict prognosis. We analyzed 580 malignant melanoma samples and demonstrated…

Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets.

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third in cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, and genetic factors. No specific genetic alterations are unequivocally linked to HCC tumorigenesis. Current standard therapies include surgical options, systemic chemotherapy, and kinase inhibitors, like sorafenib and regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint inhibitors, such as atezolizumab and pembrolizumab, s

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… Immune checkpoint inhibitors are drugs able to modify the tumor microenvironment, turning inactive immune cells into cells able to actively fight the tumor itself. … Tumor Microenvironment-Mediated Immune Evasion in Hepatocellular Carcinoma Front. Immunol. 2023 14 1133308 10.3389/fimmu.2023.1133308 36845131 PMC9950271 9. Wang Z. Wang Y. Gao P. Ding J. …

Genome-Wide DNA Methylation and Gene Expression Profiling Characterizes Molecular Subtypes of Esophagus Squamous Cell Carcinoma for Predicting Patient Survival and Immunotherapy Efficacy.

BACKGROUND: Immunotherapy is recently being used to treat esophageal squamous cell carcinoma (ESCC); however, response and survival benefits … o molecular subtypes of ESCC (S1 and S2) that are associated with distinct immune-related pathways, tumor microenvironment and clinical outcomes. Accordingly, S2 subtype patients had a poorer prognosis. A 15-gene expression signature is developed to classify molecular subtypes with an overall accuracy of 94.7% (89/94, 95% CI: 0.880-0.983). The response rate of immunothe …

Extracellular ATP is increased by release of ATP-loaded microparticles triggered by nutrient deprivation.

Rationale: Caloric restriction improves the efficacy of anti-cancer therapy. This effect is largely dependent on the increase of the extracellular ATP concentration in the tumor microenvironment (TME). Pathways for ATP release triggered by nutrient deprivation are largely unknown. Methods: The extracellular ATP (eATP) concentration was in vivo measured in the tumor microenvironment of B16F10-inoculated C57Bl/6 mice with the pmeLuc probe. Alternatively, the pmeLuc-TG-mouse was used. Caloric restriction was in vivo induced with hydroxycitrate (HC). B16F10 melanoma cells or CT26 colon carcinoma c…

Emerging drugs for the treatment of triple-negative breast cancer: a focus on phase II immunotherapy trials.

Introduction: Triple-negative breast cancer accounts for 10-20% of invasive breast cancers and is characterized by an aggressive phenotype a … g ICIs, next-generation ICIs, combination treatments with targeted agents and drugs that target the tumor microenvironment. Potential development issues are also discussed.Expert opinion: The field of immunotherapy is developing rapidly and holds great promise for patients with TNBC. Promising avenues of research currently in phase II trials include targeting multiple i …

Explicating the Pivotal Pathogenic, Diagnostic, and Therapeutic Biomarker Potentials of Myeloid-Derived Suppressor Cells in Glioblastoma.

Glioblastoma (GBM) is a malignant and aggressive central nervous tumor that originates from astrocytes. These pathogenic astrocytes divide rapidly and are sustained by enormous network of blood vessels via which they receive requisite nutrients. It well proven that GBM microenvironment is extremely infiltrated by myeloid-derived suppressor cells (MDSCs). MDSCs are a heterogeneous cluster of immature myeloid progenitors. They are key mediates in immune suppression as well as sustenance glioma growth, invasion, vascularization, and upsurge of regulatory T cells via different molecules. MDSCs are

Metformin Treatment for Diabetes Mellitus Correlates with Progression and Survival in Colorectal Carcinoma.

BACKGROUND: Diabetes mellitus is unfavorably associated with cancer risk. The purpose of this multidisciplinary project was to evaluate a po … TNM stage, coexistence of selected endocrine disorders, and metabolic abnormalities may change the tumor microenvironment and impact survival in colorectal cancer, although mechanism of these observations yet to be explained. Patients with diabetes mellitus type 2 treated with metformin may represent the altered microenvironment with specifically tuned metabolic molecu …

The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation.

There is growing appreciation of the importance of the mechanical properties of the tumor microenvironment on disease progression. However, the role of extracellular matrix (ECM) stiffness and cellular mechanotransduction in epithelial ovarian cancer (EOC) is largely unknown. Here, we investigated the effect of substrate rigidity on various aspects of SKOV3 human EOC cell morphology and migration. Young's modulus values of normal mouse peritoneum, a principal target tissue for EOC metastasis, were determined by atomic force microscopy (AFM) and hydrogels were fabricated to mimic these values. …

EphB2 activation is required for ependymoma development as well as inhibits differentiation and promotes proliferation of the transformed cell.

Our intracranial implantation mouse model of ependymoma clearly demonstrates overexpression of the ephrin receptor EphB2 in Ink4a/Arf((-/-)) supratentorial embryonic neural stem cells (STeNSCs) to be essential for transformation and disease development; however the requirement for and consequence of receptor activation on transformation and neural stem cell function were not examined. We definitively illustrate the necessity for receptor activation in cellular transformation and the importance of implantation site and microenvironment in directing ependymoma development. In vitro assays of Eph

Exosomal shuttling of miR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells.

BACKGROUND: Recent findings indicate that exosomes released from cancer cells contain microRNAs (miRNAs) that may be delivered to cells of tumor microenvironment. RESULTS: To elucidate whether miRNAs secreted from chronic myelogenous leukemia cells (CML) are shuttled into endothelial cells thus affecting their phenotype, we first analysed miRNAs content in LAMA84 exosomes. Among the 124 miRNAs identified in LAMA84 exosomes, we focused our attention on miR-126 which was found to be over-overexpressed in exosomes compared with producing parental cells. Transfection of LAMA84 with Cy3-labelled m…

Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes.

Ovarian clear cell carcinoma (OCCC) shows unique clinical features including an association with endometriosis and poor prognosis. We previo … the contents of endometriotic cysts, indicating that the OCCC signature is largely dependent on the tumor microenvironment. Induction of OCCC signature genes is at least in part epigenetically regulated, as we found hypomethylation of HNF-1beta and VCAN in OCCC cell lines. This genome-wide study indicates that the tumor microenvironment induces specific gene expression …

[Cinobufagin inhibits CD244+ macrophages to enhance T-cell activity and chemosensitivity in colorectal cancer].

Objective To investigate the effects of Cinobufotalin (Cino) on the tumor microenvironment (TME) of colorectal cancer (CRC) and the chemosensitivity to Oxaliplatin (OX). Methods We explored the clinical expression differences of CD244 in the TCGA-COAD cohort. Through UMAP dimensionality reduction analysis of single-cell sequencing data, we clarified the cellular localization of CD244 and analyzed its interaction characteristics with immune cells. In vivo experiments, a CRC tumor-bearing mouse model was established and randomly divided into 4 groups: Tu group, Cino group, OX group, and Cino com…

Decoding Sarcoma Drug Resistance: From Molecular Mechanisms to Precision Interventions.

INTRODUCTION: This study aims to systematically synthesize current knowledge on the molecular and microenvironmental mechanisms driving sarcoma drug resistance, and to evaluate emerging precision strategies for overcoming these obstacles. METHODS: We conducted a comprehensive literature review (PubMed, Web of Science, Embase; inception- 31 July 2025) using MeSH and free-text terms relating to sarcoma, drug resistance, biomarkers, and precision medicine. Inclusion criteria were peer-reviewed original or review studies in human or pre-clinical sarcoma models reporting resistance mechanisms or c

Patient-derived organoids for precision oncology in colorectal cancer: from tumor modeling to clinical translation.

Precision oncology in colorectal cancer (CRC) has been profoundly informed by genomic and transcriptomic profiling, yet molecular stratification remains only partially predictive of therapeutic benefit. This reflects a broader challenge: moving from static molecular information to dynamic, adaptive, and time-resolved predictions of drug response for individual patients along their clinical history. In CRC, this challenge is compounded by extensive inter- and intratumoral heterogeneity, clonal evolution, chromosomal instability, phenotypic plasticity and tumor-microenvironment (TME) interaction

[Multimodal integration of bioinformatic data and digital pathology as a tool for precision oncology. Part 1. Development of prognostic models based on multi-omics data and machine learning].

The article reviews current methodologies for developing prognostic models in solid tumors using bioinformatics data. Primary focus is place … lular deconvolution methods (CIBERSORT, TIMER) employed to characterize the immune landscape of the tumor microenvironment. The work discusses the potential of mathematical synthesis of molecular data to enhance the objective assessment of tumor invasive potential and explores future perspectives for personalized patient stratification within precision oncology framewor …