Presentation description

Approximately 30% of women who have been diagnosed with early-stage breast cancer develop metastatic disease, posing a significant challenge for treatment. A class of enzymes called tyrosine kinases are proteins that control many cellular functions and have roles in cancer promotion. Among the proteins implicated in promoting aggressiveness in breast cancer, short-form RON (sfRON) is a tyrosine kinase that promotes growth and metastasis when overexpressed in breast cancer cells and is associated with poor survival in patients. Developing strategies to inhibit the function of sfRON is crucial for better treatment of breast cancer. To inhibit sfRON signaling in breast cancer we will test different tyrosine kinase inhibitors as well as treatments named PROTACS (Proteolysis-Targeting Chimeras) that link enzymes to the protein of interest to ubiquitinate and degrade the targeted protein. We used the human embryonic kidney cell line 293T with overexpression of sfRON to test two different treatments with variable doses. We treated the cells with either PROTACs or tyrosine kinase inhibitors and harvested the cells to evaluate the expression and phosphorylation of sfRON through western blotting. We hypothesize that both PROTACs and tyrosine kinase inhibitors will lead to a significant reduction in the activity of sfRON in the 293T cell line. These experiments provide proof-of concept that sfRON can be targeted with our novel compounds. Future directions include testing these drugs in breast cancer cell lines as well as treatment in vivo in mice.