Background: Gemcitabine is the standard chemotherapeutic drug administered in advanced
Pancreatic Ductal Adenocarcinoma (PDAC). However, due to drug resistance in PDAC patients, this
treatment has become less effective. Over the years, clinical trials for the quest of finding novel compounds
that can be used in combination with gemcitabine have met very little success.
Objective: To predict the driving factors behind pancreatic ductal adenocarcinoma, and to understand
the effect of these components in the progression of the disease and their contribution to cell growth
Methods: With the help of systems biology approaches and using gene expression data, which is generally
found in abundance, dysregulated elements in key signalling pathways were predicted. Prominent
dysregulated elements were integrated into a model to simulate and study the effect of gemcitabine-
Results: In this study, several transcription factors in the form of key drivers of cancer-related genes
were predicted with the help of CARNIVAL, and the effect of gemcitabine-induced hypoxia on the
apoptosis pathway was shown to have an effect on the downstream elements of two primary pathway
models; EGF/VEGF and TNF signalling pathway.
Conclusion: It was observed that EGF/VEGF signalling pathway played a major role in inducing drug
resistance through cell growth, proliferation, and avoiding cell death. Targeting the major upstream
components of this pathway could potentially lead to successful treatment.