Chemoresistance remains a major challenge in addressing T-cell lymphoblastic lymphoma/leukemia (T-LBL/ALL), underscoring the necessity for novel strategies to unravel the molecular factors driving resistance. Through transcriptomic profiling, circBPTF was found to be markedly overexpressed in chemoresistant samples. Further functional experiments demonstrated that BPTF-665aa, the...
The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) pathway is critical for innate immunity, as it detects cytoplasmic DNA and drives type I interferon signaling. Pharmacological stimulation of this pathway has been recognized as a valuable approach for cancer immunotherapy, especially when used together with immune checkpoint inhibitors (ICIs). Preclinical...
Embryonic Transcription Factors (TFs) are often reactivated in cancer, driving developmental gene programs that support phenotypic plasticity. Metabolic adaptation fuels this plasticity by supplying energy and molecular building blocks for growth. RUNX2, the master regulator of bone morphogenesis, is ectopically expressed in epithelial cancer, promoting metastasis through trans...
Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer with limited therapeutic options. Although cisplatin is recommended as a first-line treatment, its clinical efficacy is hindered by the rapid development of drug resistance, highlighting the urgent need for effective strategies to overcome cisplatin resistance. We established a NEPC mouse allograft...
Protein phosphatase 2A plays a central role in modulating multiple signaling pathways, including PI3K, EGFR, Myc, WNT, JAK/STAT, RAS/MAPK, and NF-κB, which are frequently dysregulated in cancer. Although PP2A is broadly considered a tumor suppressor due to its frequent functional loss in tumors, its biological role is highly context-dependent and varies across cancer types and...
Malignant pleural mesothelioma (MPM) responds poorly to chemotherapy and is a highly progressive malignancy with a median survival time of only 6–9 months. Therefore, the development of anti-MPM tumor agents with high efficacy and low toxicity is urgent and addresses an unmet need for MPM patients. Medicinal chemistry synthesis of small molecules based on the FL118 drug platform...
Resistant mutations and amplification of the epidermal growth factor receptor (EGFR), followed by the upregulation of its translated protein undermines the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung adenocarcinoma (LUAD). This underscores that promoting EGFR protein degradation may be a promising strategy for treatment. Ubiquitin ligases database...
Acute myeloid leukemia (AML) remains a challenging hematological malignancy, with chemoresistance contributing significantly to treatment failure and relapse. The bone marrow microenvironment, particularly mesenchymal stem cells (MSCs), plays a critical role in AML cell survival and drug resistance. Although previous studies have extensively explored the MSCs differentiation, the...
Human dihydroorotate dehydrogenase (DHODH) is the rate-limiting enzyme in pyrimidine de novo synthesis and represents a promising target for cancer therapy. However, current inhibitors of DHODH have limited clinical effectiveness and adverse effects. Herein, we report NK-A 17E-233I, a novel small-molecule inhibitor of the human DHODH enzyme, identified through a prospective...
The high intra-patient heterogeneity in multifocal primary prostate cancer (PCa) has curtailed the efficacy of current treatment options. By employing twin biopsies from multiple lesions with matched patient-derived organoids (PDO) models, the PCa molecular heterogeneity was investigated. We utilized genomics, transcriptomics and machine learning (ML) approaches to elucidate and...
Increasing studies have reported that dysregulated lipid metabolism is an independent risk factor for breast cancer (BC); it would be, therefore, enlightening to investigate the relationship between metabolic reprogramming and the tumor microenvironment in the future. Ferroptosis, a novel form of programmed cell death, is characterized by glutathione (GSH) depletion and...
To spatially characterize the single-cell tumor microenvironment (TME) of salivary gland carcinomas (SGC) and identify prognostic biomarkers. SGC, including salivary duct carcinomas (SDC), acinic cell, mucoepidermoid, and secretory carcinomas, were analyzed using a 13-marker imaging mass cytometry panel. Multichannel image data from 54 primary cases and nodal metastases were...
Aberrant alternative splicing (AS) contributes to cancer stemness and progression in hepatocellular carcinoma (HCC). However, the regulatory roles of long noncoding RNAs (lncRNAs) in linking AS dysregulation to tumor stemness remain elusive. We performed integrated bulk and single-cell RNA-Seq analyses combined with functional assays to identify key lncRNAs associated with...
Gastric carcinoma ranks as the fifth most common cause of cancer-related mortality globally. Chemoresistance remains a critical barrier to treatment efficacy, driving poor survival outcomes in gastric cancer patients. Cyclin-dependent kinase 1 (CDK1) is overexpressed in several malignancies. SOX9 transcription factor plays critical roles in gastric tumorigenesis and therapeutic...
Gastric cancer remains a leading cause of cancer-related mortality in world, with advanced-stage patients facing poor prognosis despite emerging therapies. SUMOylation modification is a major post-translation modification, which is essential for cellular behaviors. However, the potential function of SUMOylation in gastric cancer (GC) and the underlying molecular mechanisms remain...
Colorectal cancer (CRC) continues to be a predominant cause of cancer-related mortality worldwide, with existing therapies constrained by systemic toxicity, resistance, and inadequate tumor targeting. While immunotherapy has potential in specific CRC subtypes, its overall effectiveness is still limited. The cyclic GMP‒AMP synthase-stimulator of interferon genes (cGAS‒STING...
Cancer-associated fibroblasts (CAFs) are key drivers of neural invasion in pancreatic cancer, yet their regulatory mechanisms remain elusive.This study explores the role of circular RNAs (circRNAs) in CAFs and their involvement in regulating neural invasion in pancreatic cancer. CAF-derived circRNAs were identified through circRNA high-throughput sequencing and quantitative real...
Ovarian cancers are the second cause of death from gynecological cancers worldwide, due to a late diagnosis combined with the development of resistance to chemotherapy. However, half of these cancers present alterations in Homologous Recombination (HR), making them sensitive to inhibitors of the PARP protein (PARPi), involved in DNA repair. Nevertheless, identifying patients who...
Genetic and epigenetic profiles are critical in managing brainstem gliomas (BSG), whose heterogeneity is far beyond the realm of the Diffuse midline glioma, H3K27 altered. Cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA)-based liquid biopsy provides minimally-invasive strategies to acquire molecular information for brain tumors, whereas there is a deficiency in techniques...
Peripheral nerve damage is intricately linked to the progression of various solid tumors. However, its effect on antitumor immunity and precise underlying mechanisms remain poorly understood. This study aimed to elucidate the effect of peripheral nerve damage and its subsequent immune-modulating effects influence on breast cancer progression. We analyzed nerve injury markers in...
Despite significant advances in targeted (BRAFi + MEKi) and immune (anti-PD1/PD-L1, anti-CTLA4, and anti-LAG3) therapies, treatment options for NRASmut melanoma remain limited. Currently, NRASmut patients rely on immune checkpoint inhibitors, classical chemotherapy, and off-label MEK inhibitors, with over 50% experiencing rapid disease progression. One of the key challenges in...
Melanoma, a highly heterogeneous malignancy, remains refractory to conventional therapies due to poorly defined molecular and metabolic drivers. Short-chain fatty acid (SCFA) metabolism influences tumor progression, yet its role in melanoma subtypes and clinical outcomes is unclear. This study aims to delineate melanoma subgroups driven by SCFA metabolic dysregulation and...
Glioblastomas (GBMs) are highly vascularized cancers. Transdifferentiation of GBM stem-like cells (GSCs) into GSC-derived endothelial cells (GdECs) contributes to GBM neovascularization. To dissect the molecular mechanisms and the signaling pathways underlying GSC contribution to tumor vascularization, we identified a three miRNA signature able to discriminate GSCs from GdECs by...
MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are key regulators of gene expression and play a crucial role in cancer progression. Recent studies have highlighted miR-423-5p as a potential modulator in hepatocellular carcinoma (HCC), especially in patients responding to sorafenib treatment. A functional interaction with the oncogenic lncRNA MALAT-1 has been hypothesized...