Combining Proteomic, Bioinformatic and Primary Cell Culture Approach for Pancreatic Cancer Drug Discovery and Evaluation

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer due to the lack of diagnostic tools at the early stage and low efficiency of current chemotherapeutic approaches. The present study combines proteomic analysis of PDAC surgical specimens and drug testing in patient-derived primary cell culture in search for effective PDAC treatment. We performed high-throughput differential proteomic analysis of tissue samples taken during operations of patients with PDAC, chronic pancreatitis and those without these diseases. Differentially expressed PDAC-specific proteins enabled us to identify biological processes specific to pancreatic cancer but not pancreatitis patients. Moreover, by comparing our proteomic data to the database of gene expression perturbation with drugs from the Library of Integrative Network-based Cellular Signatures we extrapolated potential chemotherapeutic agents for PDAC treatment. The efficiency of the drugs was evaluated using primary patient-derived PDAC cell cultures. We have also extracted from the data a number of already known as well as new potential PDAC-specific biomarkers. The results show the promising potential of this bioinformatic approach for anticancer drug discovery and evaluation.

This work was supported by DiaKASA project (Nr. SEN-01/2016) of the Research Council of Lithuania.