Guest Editors
Prof. Seiji Okada
Email: okadas@kumamoto-u.ac.jp
Affiliation: Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-0811, Japan
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Research Interests: innate immunity, hematopoietic stem cells, tumor microenvironment, NK cell-based immunotherapy, humanized mouse models, viral-associated malignancies, cellular differentiation and plasticity, epigenetic regulation in cancer
Dr. Kulthida Vaeteewoottacharn
Email: Kulthidava@kku.ac.th
Affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
Homepage:
Research Interests: cholangiocarcinoma, drug resistance, glycosylation, natural compounds, PI3K/AKT/mTOR signaling, tumor microenvironment, angiogenesis inhibition, immunotherapy
Summary
Cholangiocarcinoma (CCA) is a highly aggressive and heterogeneous malignancy characterized by complex cellular and molecular mechanisms driving its progression. Despite recent advances, the understanding of CCA cell origin, differentiation pathways, tumor microenvironment interactions, and drug resistance mechanisms remains incomplete, posing significant challenges for developing effective therapies. This special issue aims to bring together cutting-edge research that dissects the cellular biology of CCA, elucidates its regulatory molecular networks, and explores novel therapeutic strategies at the cellular level.
We welcome original research and review articles that focus on the cellular and molecular mechanisms of CCA, including but not limited to:
1. Cell Origin, Differentiation, and Transformation Mechanisms of CCA
· Cellular origin of CCA: Cholangiocytes, hepatic progenitor cells, or dedifferentiated hepatocytes.
· Role of epigenetic modifications (DNA methylation, histone modifications, non-coding RNAs) in CCA differentiation.
· Epithelial-mesenchymal transition (EMT) and its impact on CCA invasion and metastasis.
· Single-cell sequencing studies revealing CCA heterogeneity and plasticity.
2. Key Signaling Pathways Involved in CCA Progression
· Notch signaling in cholangiocyte fate determination and tumor progression.
· Wnt/-catenin activation and its role in CCA stemness and proliferation.
· Hippo-YAP/TAZ signaling in CCA growth, survival, and drug resistance.
· PI3K/AKT/mTOR pathway in metabolic adaptation and targeted therapy responses.
· Crosstalk between TGF-, MAPK/ERK, JAK/STAT, and other signaling cascades in CCA progression.
3. Impact of Tumor Microenvironment on CCA Cell Behavior
· Role of cancer-associated fibroblasts (CAFs) in extracellular matrix remodeling and tumor progression.
· Immune evasion mechanisms: PD-L1 regulation, T-cell infiltration, and tumor-associated macrophages (TAMs).
· Hypoxia-driven metabolic reprogramming and its effects on CCA cell survival and therapy resistance.
· Interaction between immune cells, stromal components, and CCA cells in shaping tumor progression.
4. Mechanisms of Drug Resistance and Metabolic Adaptation in CCA
· Molecular mechanisms underlying chemotherapy and targeted therapy resistance.
· ABC transporters and efflux-mediated drug resistance.
· Metabolic rewiring: Glycolysis, glutamine metabolism, and lipid biosynthesis in CCA survival.
· Epigenetic regulators (miRNAs, lncRNAs, circRNAs) in CCA drug resistance and adaptation.
5. Development and Application of Preclinical Cellular Models for Drug Screening and Mechanistic Studies
· 3D organoid models and patient-derived CCA cell lines for disease modeling.
· Co-culture systems integrating CCA cells with CAFs, immune cells, and extracellular matrix components.
· High-throughput drug screening platforms for personalized therapy development.
· Application of CRISPR/Cas9 and single-cell sequencing to identify novel therapeutic targets.
By focusing on the cellular mechanisms driving CCA progression and resistance, this special issue aims to provide novel insights into the biology of CCA and its therapeutic vulnerabilities. We encourage contributions that leverage innovative cellular models and mechanistic studies to advance translational research and precision medicine approaches for CCA treatment.
Keywords
cholangiocarcinoma (CCA), cellular mechanisms, tumor microenvironment, drug resistance, preclinical models, signal pathways, metabolic reprogramming, therapeutic strategies
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