Project Update (7/2016)

Researchers have discovered that altering the process of autophagy can change the way tumor cells respond to therapy, but as my own research has found not all cancer cells respond the same way to blocking this survival pathway. Therefore, a one-size-fits-all approach to altering autophagy is not appropriate for cancer treatment, particularly in kids. It is a complex process, which makes studying its role in tumor cell death challenging. This project built on exciting data I uncovered that showed I am able to identify specific pediatric tumors that are dependent this survival pathway, making those patients potentially ideal candidate for future clinical trials incorporating autophagy inhibition drugs.

Using novel laboratory techniques in addition to using patient tumor samples and a mouse model of pediatric brain tumors, the combination of these research approaches is the first step in the development of future clinical trials. I have been able to show that cancer cells with specific genetic mutations in the BRAF pathway are more sensitive to autophagy inhibition than cells without the mutation, and that blocking autophagy in combination with other drugs improves tumor cell killing. Moving beyond treating cancer cells in a plastic dish, I generated brain tumors in a mouse model which allowing me to mimic as near as possible how tumors would responds in a pediatric patient, and treat them in mini-clinical mouse trials. I have also been able to test primary patient tumor samples to show effectiveness directly on fresh human tumors. Early results from the mini-clinical mouse trials and testing of primary patient tumors are encouraging that the combination therapies improve tumor cell kill in our mouse patients.