Investigating the Interactions of Glutamine Amidotransferases and MEK ERK Signaling to Develop Novel Therapeutic Strategies for NF1-Associated Tumors
Abstract
People with the genetic condition neurofibromatosis type I (NF1) have a considerably increased risk for cancer compared to the general population. Many such tumors cannot be removed with surgery and do not respond well to traditional chemotherapy. The goal of the proposed research is to investigate whether a new type of medicine called a glutamine amidotransferase inhibitor can effectively treat tumors in NF1 patients. Glutamine amidotransferases, of which there are at least 8 in human cells, are metabolic proteins that use the amino acid glutamine to build nutrients that cancer cells need to grow and survive. Our prior research has shown that glutamine amidotransferase inhibitors, including the compound DRP-104, are effective treatments in tumor models, but this finding has not yet been explored thoroughly in NF1-associated tumor models including malignant peripheral nerve sheath tumor or glioma. The goal of the proposed research is to investigate the interactions of glutamine amidotransferases with signaling pathways that are active in NF1-associated tumors and to examine how effective DRP-104 is as a single agent or in rational combinations in NF1-associated tumor models both in cells and in animal models. In this Year 1 progress report we describe efforts to date in these investigations. Both cell based studies and animal studies using DRP-104 have been initiated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1218480
Entities
People
- Kathryn Lemberg
Organizations
- Johns Hopkins University