eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2026-04-27 19 2 71572 article Binoy Varghese Cheriyan 1 Kaniga Pandi 1 Kunal Rupesh Kumar Kataria 1 Yokesh Shanmugam 2 Maha Swetha Kannuchamy 2 Mahalakshmi Sundarraj 1 Department of Pharmaceutical Chemistry, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India. Department of Pharmacology, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India. Pancreatic cancer is one of the most lethal malignancies, accounting for approximately 3–4% of all cancers but nearly 7–8% of cancer-related deaths worldwide, with a 5-year survival rate of less than 12%. Its aggressive biology, early metastatic spread, and profound resistance to chemotherapy contribute to poor clinical outcomes. Due to these challenges, in vitro pancreatic cancer cell line models have become indispensable tools for elucidating molecular mechanisms underlying tumor progression and drug resistance. This review comprehensively evaluates three widely used pancreatic cancer cell lines PANC-1, MiaPaCa-2, and BxPC-3 highlighting their distinct molecular, phenotypic, and genetic characteristics and their relevance in anticancer drug discovery. PANC-1 cells, characterized by KRAS mutations and high mesenchymal marker expression, are extensively utilized to study epithelial–mesenchymal transition (EMT), migration, and invasiveness. MiaPaCa-2 cells exhibit enhanced glycolytic activity, stemness-associated markers, and pronounced chemoresistance, making them valuable for investigating cancer stem cell behavior and metabolic adaptations. In contrast, BxPC-3 cells, which are KRAS wild-type, serve as an important model for assessing drug sensitivity and therapeutic response mechanisms, particularly to gemcitabine and targeted agents. Comparative analyses across these models have significantly advanced understanding of key drug resistance pathways, including EMT-driven resistance, altered metabolic signaling, and survival pathway activation, and have facilitated preclinical screening of standard chemotherapeutics and emerging novel compounds. Furthermore, cross-model comparisons provide insights into tumor heterogeneity and support the identification of predictive biomarkers for therapeutic outcomes. Although conventional cell lines remain essential molecular tools, their inability to fully recapitulate the tumor microenvironment limits translational relevance. Therefore, integrating advanced systems such as organoids, patient-derived xenografts, and co-culture models is crucial to bridge the gap between preclinical research and clinical application and to improve therapeutic strategies for pancreatic cancer. https://biomedpharmajournal.org/vol19no2/mechanisms-of-tumor-progression-and-drug-resistance-in-pancreatic-cancer-models-panc-1-miapaca-2-and-bxpc-3-a-review/ Anticancer drug screening BxPC-3 Drug resistance MiaPaCa-2 Pancreatic cancer PANC-1 Targeted therapy