Peptide-Drug Conjugate as a Targeted Therapeutic for Malignant Peripheral Nerve Sheath Tumor
Abstract
This project addresses the area of emphasis on Therapy: Identify novel therapeutic strategies, including drug repurposing. Malignant peripheral nerve sheath tumors (MPNST) is considered a high-grade sarcoma with a fairly poor prognosis (5-year survival of less than 50%) and is a leading cause of increased death for neurofibromatosis type 1 patients. The occurrence of MPNST is rare with an estimated incidence of 1.46 per 1,000,000 individuals, which falls under Congressionally Directed Medical Research Programs rare cancers definition. Although surgery to remove neurofibromas is the main treatment for MPNST, its complete surgical removal is almost impossible. For unresectable or metastatic diseases, chemotherapeutic drugs are only marginally effective (with a response rate of less than 21%), and initial responses to therapy are usually short-lived with a recurrence rate of 40%-65%, followed by rapid progression and death. As such, 5-year overall survival rates remain low (the 5-year survival is less than 50%). Currently, there are no effective systemic therapies for MPNST patients. Therefore, novel efficacious therapeutic approaches are urgently needed. In this proposed research, we will develop and test peptide-drug conjugate (PDC), a new type of targeted therapeutic that could help treat patients with MPNST. PDC is a chemical combination of two types of molecules – a peptide capable of selectively binding MPNST cells and a chemotherapy drug that is toxic to cancer cells. Such approach will make the drugs primarily accumulate in the tumors while simultaneously decreasing the off-target effects. At the end of this project, we will obtain proof in vitro that this approach works. We expect that another 4 years will be needed for further optimization and animal testing before putting into human clinical trials. If successful, PDC will make chemotherapy more efficacious and much safer, and will have a tremendous impact on the improvement of survival rate and quality of life of patients with MPNST.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210941
Entities
People
- Tsung Shih
Organizations
- United States Army
- University of California, Davis