In Vitro Elucidation of Drug Combination Synergy in Treatment of Pancreatic Ductal Adenocarcinoma

Background/Aim: Advances in therapies targeting proteins and pathways affected by genetic alterations has raised the possibility of personalized cancer treatments. Materials and Methods: The efficacy of targeting molecular aberrations was determined in the pancreatic ductal adenocarcinoma (PDAC) cell line, CAPAN2. Two mutations were targeted, KRAS (p.G12V) and ABL1 (p.G1060D), and cells were treated with regorafenib and trametinib, individually and in combination. Results: Exposure to either drug significantly increased cell death compared to the current standard of care, gemcitabine. Treatment with combinations of the drugs led to significant increases in cell death compared to either monotherapy. Strong additive/synergistic interactions were observed across a range of dosages and ratios, reducing dose requirements with potential clinical relevance. Conclusion: The data obtained in this PDAC cell model: i) support the use of matched monotherapies; ii) indicate the effectiveness of matched combination therapies; and iii) provide potential proof-of-concept for precision medicine approach to cancer treatment.