JAK/STAT Activation Drives CIC-Rearranged Sarcoma
Abstract
CIC-rearranged sarcoma is a rare but lethal tumor affecting children and young adults, which falls into the Fiscal Year 2021 Rare Cancers Research Program Focus Area Therapy this proposal will address. Currently there is no standard therapy for this aggressive disease and patients generally succumb within first 2 years of diagnosis. In this application we dissect the mechanism of the CIC-fusion proteins that are the drivers of this disease. Unfortunately, due to the rarity of the disease, very little functional work is known about how these fusion oncoproteins cause the disease. We provide strong evidence to show for the first time that the CIC fusion-induces activation of the JAK/STAT pathway, an important signaling pathway involved in cancer. Importantly, this pathway is targetable in patients. We will utilize various patient-derived CIC-fusion cultures and pre-clinical animal models to demonstrate the importance of this pathway in driving the progression of this lethal tumor. The findings from this proposal will provide promising pre-clinical drug/targets within the JAK/STAT pathway that can directly be translated into the clinic as novel therapeutics for these patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211071
Entities
People
- Severa Bunda
Organizations
- United States Army
- University Health Network