2008 UALC
E Thompson, PhD
Mayo Clinic Cancer Center, Jacksonville
Research Project:
The Role of Phospholipase D1 in EGFR Addiction
Summary:
Dr. E. Aubrey Thompson studies a protein called phospholipase D1 (PLD1). He has observed that inhibition of PLD1 results in death of lung cancer cells that are dependent on EGFR even when they are resistant to EGFR inhibitors. He will determine whether drugs that can inhibit PLD1 cooperate with EGFR inhibitors to improve the killing of tumor cells.
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Final Report
Dr. Thompson has gained important insight into how PLD1 is involved in cell growth and invasion. The data shows a complex relationship between PLD1 and the protein kinase c (PKC) pathway to control cell invasion. Furthermore, the activity of PLD1 seems to control a subset of responses in the PKC pathway, only involved in invasion and metastasis. With this understanding of PLD1’s mechanism, Dr. Thompson investigated lung cancer cells with EGFR mutations to determine if a PLD1 inhibitor could cooperate with EGFR inhibitors. In cells with EGFR-activating mutations, depletion of PLD1 completely blocked the growth of unanchored cells — the cells involved in metastasis and invasion.