STUDIES OF AXL, HER2, AND PDGFRβ RECEPTOR TYROSINE KINASES IN MUTANT KRAS-DRIVEN PANCREATIC CANCER IN VITRO

Abstract

This project proposes to demonstrate the overexpression of the selected tyrosine kinase receptor, RTK, (AXL, HER2, and PDGFRβ) and their participation in oncogenic KRAS driven pancreatic cancer in vitro. The experimental design is to analyze the mRNA expressions of using q-PCR and protein expression using flow cytometry and ELISA. The participation of these selected RTK in this type of cancer will be demonstrated after knockout of their genes separately using the CRISPR/Cas9 gene editing system followed by an MTT proliferation assay to monitor any change in the proliferation rate after inactivating these genes. The inhibition of the selected RTK using their inhibitors, which are currently available for pancreatic cancer treatment, will also be used to demonstrate the participation of these selected RTK and will be evaluated to determine if further future drug development is needed. Therefore, R428, Lapatinib, and Sunitinib inhibitors will be used to inhibit AXL, HER2, and PDGFRβ, respectively. The confirmation of this hypothesis depends on the reduction of the proliferation rate in cell lines and may lead to new therapeutic strategies for pancreatic cancer.