Single-Cell Sequencing Unravels Pancreatic Cancer: Novel Technologies Reveal Novel Aspects of Cellular Heterogeneity and Inform Therapeutic Strategies

作者：Kexin Chen, Zeyu Chen, Jinai Wang, Mo Zhou, Yun Liu, Bin Xu, Zhi Yu, Yiming Li, Guanhu Yang, Tiancheng Xu · 发表于：Biomedicines · 年份：2025 · DOI：10.3390/biomedicines13123024 · 被引用次数：8 · 研究领域：Single-cell and spatial transcriptomics、Pancreatic and Hepatic Oncology Research、Cancer Cells and Metastasis

Single-cell sequencing (scRNA-seq) has emerged as a pivotal technology for deciphering the complex cellular heterogeneity and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC), positioning it as a critical tool for informing novel therapeutic strategies. This review explores how scRNA-seq reveals diverse cellular subpopulations and their functional roles within the PDAC TME, including malignant epithelial cells with transitional phenotypes, heterogeneous cancer-associated fibroblasts (CAFs), functionally distinct immune cells such as tumor-associated neutrophils (TANs) and macrophages (TAMs), and actively participating neural components like Schwann cells. These cellular constituents form specialized functional units that drive tumor progression, immune evasion, neural invasion, and therapy resistance through metabolic reprogramming, immunosuppressive signaling, and cellular plasticity. The review further examines technological advances in single-cell sequencing from 2023 to 2025, focusing on sample preprocessing innovations, multi-omics integration (combining transcriptomics with epigenomics and proteomics), spatial resolution enhancements, and customized computational tools that address PDAC-specific challenges. Clinically, single-cell sequencing enables precise cellular subtyping, identification of novel biomarkers, and development of personalized therapeutic approaches, including combination therapies targeting specific cellular subpopulations and th...