The transcriptional regulatory circuit as a driver and therapeutic target in CML blast crisis Patients with blast crisis in chronic myeloid leukemia (CML) exhibit an extremely poor prognosis, with median survival of only a few months and limited therapeutic options. Dysregulated transcriptional regulation plays a pivotal role in driving blast crisis progression. In this study, we performed histone modification and transcriptomic high-throughput sequencing on bone marrow cells derived from chronic and blast-phase CML patients,… bioRxiv Cancer Biology November 7, 2025 Original source
IMMUNIA: A Multi-LLM Reasoning Agent for Immunoregulatory Surfaceome Discovery Biomarker discovery for immunotherapy often requires reasoning across complex immune contexts. We present IMMUNIA, a multi-large-language-model (multi-LLM) reasoning agent designed to identify immunoregulatory surfaceome genes through interpretable, biologically grounded analysis. The term IMMUNIA originates from the fusion of Immune and Noeia (the Greek concept of perception and understanding), defining an AI system that perceives, reasons, and interprets the immune landscape… bioRxiv Cancer Biology November 7, 2025 Original source
Suppression of Glucosylceramide Synthase Reverses Drug Resistance in Cancer Cells Harbor Homozygous p53 Mutants Glucosylceramide synthase (GCS) catalyzes ceramide glycosylation in response to cell stress that produces glucosylceramide and other glycosphingolipids. GCS overexpression is a cause of drug resistance and enriches cancer stem cells (CSCs) during cancer chemotherapy. Previous studies showed that GCS modulates expression of p53 mutants and oncogenic gain-of-function (GOF) in heterozygous knock-in cell models (TP53 R273H-/+). However, it is unclear whether… bioRxiv Cancer Biology November 7, 2025 Original source
Cytoskeleton remodeling caused by keratin dysregulation triggers tumor aggressiveness via promoting genomic instability and cellular adaption Cellular architecture depends on keratin intermediate filament as a fundamental component, which offers essential mechanical support to fight environmental stresses. Our previous research demonstrated that keratin fusion variants increase tumor aggressiveness through enhanced cancer stemness in oral squamous cell carcinoma. The proper functioning of keratins plays an essential role in maintaining cell structure while determining cell fate. The present study… bioRxiv Cancer Biology November 7, 2025 Original source
AXL mediates mast cell survival and resistance to tyrosine kinase inhibitors in mastocytosis Mastocytosis is a clonal disorder driven by KIT mutations, but resistance to tyrosine kinase inhibitors (TKIs) remains a major challenge. Following the discovery of an AXL L197M mutation in a patient with congenital aggressive mastocytosis, we demonstrated unexpected wild-type AXL expression in neoplastic mast cells (MCs) across mastocytosis subtypes, challenging current views concerning mastocytosis pathophysiology. AXL was undetectable in steady-state… bioRxiv Cancer Biology November 7, 2025 Original source
Design and Development of DNA Damage Chemical Inducers of Proximity (DD-CIP) for Targeted Cancer Therapy Many chemotherapies are effective against cancers that display high levels of genome instability by disrupting or overwhelming the DNA damage response to induce cell death. PARP inhibitors (PARPi) exploit this vulnerability by stalling DNA repair particularly in homologous recombination (HR)-deficient cancer cells. Although PARPi are now used to treat BRCA1/2-mutated cancers such as ovarian and breast cancers, they are still… bioRxiv Cancer Biology November 7, 2025 Original source
Agent-based simulations of lung tumour evolution suggest that ongoing cell competition drives realistic clonal expansions Computational simulations of tumour evolution are increasingly used to infer the rules underlying cancer growth, with the goal of one day recommending tailored treatments. To make reliable inferences, such models must be able to reflect the properties of real tumours. Recent work has shown that lung tumours undergo frequent and late subclonal expansions, which are associated with poor prognosis. This… bioRxiv Cancer Biology November 7, 2025 Original source
Mineralocorticoid and glucocorticoid receptor interaction drives TGFB1-induced triple-negative breast cancer progression to metastasis In triple-negative breast cancer (TNBC), p38 MAPK phosphorylates the glucocorticoid receptor (GR) at N-terminal Ser134 in response to cytokines, such as TGF{beta}1. Phospho-Ser134-GR (pSer134-GR) regulates genes that promote migratory/invasive behavior and altered metabolism. In addition to acting as ligands for GR, glucocorticoids also activate closely-related mineralocorticoid receptors (MR). Elevated MR activity via its physiological ligand aldosterone (aldo), mediates hypertension, inflammation… bioRxiv Cancer Biology November 7, 2025 Original source
Integrative transcriptomic analysis identifies miR-642a-5p as a regulator of POFUT1 expression in colon cancer Background: Colorectal cancer (CRC) is one of the most common and deadly cancers worldwide, underscoring the urgent need for novel biomarkers and therapeutic targets. Protein-O-fucosyltransferase 1 (POFUT1) is increasingly recognized as an oncogenic driver in CRC, but the upstream regulatory mechanisms responsible for its overexpression remain poorly understood. Objective: We aimed to identify a reproducible miRNA signature potentially regulating POFUT1… bioRxiv Cancer Biology November 7, 2025 Original source
TAK1 is a key regulator of oncogenic signaling and differentiation blockade in rhabdomyosarcoma Rhabdomyosarcoma (RMS) is a malignant soft tissue sarcoma with a skeletal muscle phenotype, accounting for approximately 50% of all pediatric soft tissue sarcomas and 8% of all childhood cancers. Although RMS cells express myogenic regulatory factors, they fail to undergo terminal differentiation into mature muscle cells. Transforming growth factor {beta}-activated kinase 1 (TAK1) is a major signaling protein that activates… bioRxiv Cancer Biology November 7, 2025 Original source
Therapeutic Eradication of Cancer-associated Fibroblasts Inhibits in vivo progression of Pancreatic Cancer Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with an unmet medical need. therapeutic elimination of cancer associated fibroblasts (CAFs), key drivers of tumor aggressiveness, has been the focus of recent studies. However, the inherent heterogeneity and plasticity of CAFs have hampered the development of CAF-targeted therapies. Clemastine, an FDA-approved cationic amphiphilic drug, is known to elicit cytotoxic lysosomal membrane… bioRxiv Cancer Biology November 7, 2025 Original source
Immune infiltration is linked to increased transcriptional activity and distinct metabolic profiles in chordomas Chordomas are ultra-rare cancers from the axial skeleton with limited treatment options. Chordomas can exhibit immunogenic features, and immune checkpoint blockade has demonstrated clinical activity in some patients, yet the determinants of these responses remain poorly understood. We aimed to elucidate the biological basis of immunogenicity in chordomas through spatial transcriptomic and metabolomic analyses. We applied GeoMx digital spatial profiling… bioRxiv Cancer Biology November 7, 2025 Original source
Identification and validation of liquid biopsy-based methylation biomarkers: a germ cell tumor subtype-specific study Human germ cell tumors (GCTs) occur in infants, children, and adults, and present as germinomatous and/or non-germinomatous (embryonal carcinoma, teratoma, yolk sac tumor (YST), and choriocarcinoma) histologies at gonadal or extragonadal locations. Accurate subtyping is crucial for prognosis and treatment, but current clinical biomarkers lack sensitivity and specificity (serum proteins) or require a tissue biopsy (immunohistochemistry). Hence, less-invasive and improved… bioRxiv Cancer Biology November 7, 2025 Original source
Longitudinal investigation of prostate tumor spheroid proliferation with dynamic line-field optical coherence tomography Recently, it has become widely recognized that culturing cancer cells in vitro in small, 3D aggregates known as tumor spheroids provides a more physiologically relevant model of in vivo tumor behavior compared to 2D monolayer cultures. Dynamic optical coherence tomography (dOCT) is a non-invasive imaging modality that, by analyzing temporal fluctuations in the light scattered from biological tissue, does not… bioRxiv Cancer Biology November 7, 2025 Original source
Differential Wnt/β-Catenin Signaling via TCF7L2/LEF1 Binding Specificity Shapes Cellular and Tumor Phenotypes The mechanisms by which Wnt/{beta}-catenin signaling regulates gene expression in a tissue- and context-specific manner remain poorly understood, limiting our ability to target the aberrant cell growth typical of many Wnt-driven cancers. Here we focus on malignant liver tumors driven by activating CTNNB1 ({beta}-catenin) mutations that nevertheless display distinct phenotypic states and Wnt outputs. By profiling patient-derived organoids via single-cell… bioRxiv Cancer Biology November 7, 2025 Original source
Cell-line specific role of Cathepsin B in triple-negative breast cancer growth, invasion and response to chemotherapy Cathepsins are papain-family cysteine proteases known to play a cell-intrinsic role in protein degradation in the lysosome, as well as in digesting ECM and surface proteins after being secreted. Both of these functions are known to mediate pro-tumorigenic effects of CTSB in a range of cancers. Here, we specifically investigate the role of CTSB in TNBC, an aggressive subtype of… bioRxiv Cancer Biology November 7, 2025 Original source
Bronsted-basic small molecules activate GTP hydrolysis in Ras Q61 mutants The RAS oncogenes (KRAS, HRAS, NRAS) are among the most frequently mutated genes in human cancer, affecting over three million patients annually. Therapeutic development has largely focused on inhibitors for KRAS codon 12 mutations (G12C/D/V/S/R) which are key drivers in lung, colorectal, and pancreatic cancers. In contrast, mutant-selective inhibitors for Q61 variants remain elusive. A common mechanistic feature of G12… bioRxiv Cancer Biology November 7, 2025 Original source
A switch from histone methyltransferase-EZH2 to demethylase KDM6A activity marks reinitiation of proliferation of drug treated colorectal cancer cells Colorectal cancer (CRC) is one of the deadliest cancers, ranking third in cancer incidence worldwide. These tumor cells often adopt unique strategies under drug stress to attain a reversible drug-tolerant state and evade cell death. However, the molecular adaptations associated with this transitory emergence of the drug-tolerant state remain elusive. Herein, epigenetic alterations often dictate such reversible dynamic changes, and… bioRxiv Cancer Biology November 7, 2025 Original source
Cascade-Targeting Nanoparticles for Reversing Chemoresistance in Osteosarcoma Osteosarcoma is the most common primary malignant bone tumor in adolescents. Despite significant progress in multimodal therapies, its clinical efficacy remains severely limited by chemotherapy resistance. To overcome the barriers of DNA repair and drug efflux associated with resistance, we developed a biomimetic nanoplatform with cascade targeting capability, termed TAT-mPDO@cRGD-M. This system employs a polydopamine (mPDA) core with strong photothermal… bioRxiv Cancer Biology November 7, 2025 Original source
Phospho 394Y LCK flow-cytometry readout predicts dasatinib sensitivity in paediatric T-cell acute lymphoblastic leukaemia Children with T-cell acute lymphoblastic leukaemia (T-ALL) who relapse or fail induction have poor outcomes. A subset of cases show glucocorticoid resistance reversible by dasatinib through inhibition of LCK-dependent signalling. To identify a practical biomarker of dasatinib response, we compared in-vitro drug sensitivity with basal phosphorylation of pre-TCR pathway proteins in 28 paediatric T-ALL patient-derived xenografts (PDX). Phospho-flow cytometry quantified… bioRxiv Cancer Biology November 7, 2025 Original source