This thesis investigates the pharmacodynamic interactions of the FOLFIRINOX regimen and the role of microRNAs (miRNAs) in pancreatic cancer models. FOLFIRINOX, a combination of 5-Fluorouracil, oxaliplatin, and SN-38, was evaluated for its pharmacodynamic interactions across various pancreatic cancer cell lines. Synergistic interactions were observed between oxaliplatin and SN-38 in PANC-1 and MIAPaCa-2 cells, while the triple combination showed strong synergy in MIAPaCa-2 and borderline additive effects in PANC-1. Antagonistic interactions were noted in primary PIN-127 and 3D PANC-1 models, underscoring the complexity of these drug interactions and the need for further optimisation in clinical settings. Parallel studies focused on the role of miRNAs in pancreatic cancer. A global comparison of miRNAs in pancreatic tumours, adjacent normal tissue, and patient-derived xenograft models identified several differentially expressed miRNAs which have not been previously linked to pancreatic cancer. Investigation into one miRNA, miR-6831-5p in particular showed that its overexpression in PANC-1 cells altered mitochondrial bioenergetics, purine nucleotide homeostasis, and apoptosis, potentially affecting gemcitabine sensitivity. These findings highlight the intricate interplay between miRNAs, metabolic pathways, and drug responses, offering new insights into pancreatic cancer. Further investigations revealed differential miRNA processing efficiencies of stably transfected pancreatic cancer cells. While vectors successfully increased miR-708 levels, they failed to elevate mature forms of miR-29b, -1290, -2467, and -6831 due to a block at the pre-miRNA stage. However, synthetic pre-miRNA mimics effectively generated mature miRNAs, indicating potential strategies to overcome miRNA processing barriers. These results demonstrated the distinct behaviour of different miRNAs with the same vector in the same cell line, the same miRNA between the two vector designs, and with the same miRNA across different cell lines. In addition, these findings on the structural and sequence differences between successful and non-successful vector designs could help inform future chimeric miRNA design strategies and act as a guide to other researchers on the intricate processing dynamics that can impact vector efficiency. By linking the investigation of drug interactions with insights into the role of miRNA, this thesis contributes to a more nuanced understanding of pancreatic cancer treatment and provides actionable strategies for enhancing therapeutic efficacy.