Rapid Drug Sensitivity Profiling via a Novel High-Success-Rate Culture Method for Patient-Derived Pancreatic Cancer: An Exploratory Preclinical Platform for Advancing Clinical Applications and Drug Development

Highlights: What are the main findings? A cost-effective, hydrogel-free adherent culture system for patient-derived pancreatic cancer cells was established with a high success rate exceeding 90%. The cultured cells maintain essential oncogenic KRAS mutations and exhibit a consistent six-gene malignancy signature, including fibroblast activation protein (FAP) and WNT5A. What are the implication of the main findings? This platform enables rapid and accurate drug sensitivity profiling that shows potential associations with clinical trends, serving as a practical tool for functional precision medicine. The high-purity cancer cell population supports an exploratory preclinical platform and biomarker validation for novel therapeutics, such as antibody–drug conjugates and immune checkpoint inhibitors. Pancreatic cancer is a highly intractable malignancy that necessitates personalized treatment strategies. Conventional patient-derived models, such as three-dimensional organoids, are often limited by intellectual property constraints and high costs. In this study, we developed an affordable adherent culture system for patient-derived pancreatic cancer cells using a proprietary medium and laminin-coated dishes. Primary cultures were successfully established from 28 patients with pancreatic ductal adenocarcinoma, exceeding a 90% success rate. Validation of eight samples confirmed maintenance of epithelial cell adhesion molecule expression and preservation of oncogenic KRAS mutations. Transcriptomic profiling revealed consistent upregulation of a six-gene signature (FAP, IGFBP5, PRRX1, SPARC, WNT5A, and ADAMTS12), which is associated with malignancy. In vitro drug sensitivity assays revealed interpatient heterogeneity with preliminary clinical associations. In conclusion, this simplified platform provides high-purity cancer cells and serves as a functional precision medicine tool. Beyond conventional chemotherapy, this platform has the potential to support applications ranging from biomarker validation and exploratory preclinical testing of novel therapeutics, including immune checkpoint inhibitors and antibody–drug conjugates. This optimization can lead to personalized therapeutic strategies for pancreatic cancer.