INDER VERMA, Ph.D.
The Salk Institute for Biological Studies
“Novel Therapies for Glioblastoma”
It is widely believed that the development of animal models that are more predictive of therapeutic efficacy in humans, and identification of key molecular drivers of tumor growth and malignancy will lead to significant clinical advances in the treatment of Glioblastoma Multiforme (GBM). The focus of Dr. Verma’s translational research project is two-fold: 1) evaluate the still largely unknown role of Aurora-A in gliomagenesis, and 2) determine if Aurora-A kinase is a key driver of the cancer cell behavior and hence may serve as a target for therapeutic intervention for GBM.
Many fundamental processes in cancer cells are regulated by phosphorylation of proteins, including the cell’s response to DNA damage, DNA replication, cell cycle regulation, and signaling pathways that govern a cell's commitment to either live or die. Proteins are phosphorylated by a specific class of proteins comprised of many different enzymes called protein kinases.
Dr. Verma and his lab found that Aurora-A kinase is overexpressed in many human GBM tissues and cell lines and hypothesize that this overexpression may play a critical role in tumor formation in glioma. They will test this idea in a novel GBM model they developed by stereotactically injecting Aurora-A into the brains of mice with a p53+/- genetic background using a Cre-inducible lentiviral vector and examining impact on tumor formation.
If Aurora-A kinase plays a key role in the genesis of malignant glioma, it may be possible to change the course of the disease by inhibiting its function. Dr. Verma will use his novel mouse GBM model to test the in vivo antitumor efficacy of two Aurora-A kinase inhibitors currently in clinical trial in patients with other malignant solid tumors. The lab isolated the tumor cells derived from the GBM mouse models and found they possess properties of brain tumor-initiating cells, or cancer stem cells (CSCs). Therefore, CSCs should be the targets of the Aurora-A kians inhibitor therapy.
In summary, Dr. Verma and his team will evaluate the still largely unknown role of Aurora-A in gliomagenesis. In this study, Dr. Verma’s team will determine if Aurora-A kinase is a key driver of the cancer cell behavior and hence may serve as a target for therapeutic intervention for GBM.