Silpa Gampala, PhD

Patients with Neurofibromatosis Type 1 (NF1) disease are at a higher risk of developing malignant peripheral nerve sheath tumors (MPNSTs) than the general population (10% vs 0.01%, respectively). 10-20% of these are diagnosed in children. Complete surgical removal of the tumor is the mainstay of treatment. For tumors that are located in deeper parts of the nervous system, surgery is not possible. In such cases, chemotherapy can be used, but MPNSTs respond poorly to existing standard of care therapies like ifosfamide and doxorubicin. Therefore, there is need for new therapies and approaches. Nf1 gene, which suppresses a protein called RAS, is lost in these patients and the resulting overactive RAS reprograms growth-promoting pathways including metabolism. RAS dependent cancers like MPNSTs are highly aggressive and metastatic as the tumor and surrounding cells are constantly metabolizing energy sources like glucose and glutamine for their growth and spread. Therefore, we hypothesize that metabolism plays a critical role in driving MPNST progression and that obstructing nutrients required for the growth and spread of these tumors will slow or suppress this disease. In this study we propose to decode the dependencies of tumor cells and cells surrounding the tumor on different energy sources like glucose, glutamine, and others. With this information, it is possible to intercept the pathways that generate energy prior to disease progression to prohibit tumor growth and spread.