Targeting Noncoding RNAs in Advanced Uveal Melanoma
Abstract
The proposed research addresses two of the Focus Areas Biology and Etiology and Therapy. Uveal melanoma (UM) is a rare tumor arising from melanocytes in the eye (iris, ciliary body, and choroidal). Although recent advances in targeted therapy and immunotherapy have improved the survival of skin melanoma patients, they are not as effective for UM. The long-term survival rate for patients with UM is poor. Nearly half of primary UM tumors migrate to other organs; the chief target is the liver. Furthermore, there are no effective therapies for metastatic UM. Because cancer cells resemble embryonic cells in many ways, such as ability to invade adjacent tissues and migrate to remote places, our lab focuses on understanding biological processes that are common for malignant tumors and early embryos. We have identified RNAs produced by genes on the X chromosome (Xq26.3). These RNAs enable embryonic cells to change shape, lose contact with neighboring cells, and migrate to other places during embryonic development. Elevated levels of these RNAs are linked to poor prognosis in UM. Therefore, we will study whether these RNAs are responsible for the invading and migratory properties of UM cells. We will test whether UM cells will migrate and form a tumor in the liver after we neutralize these RNAs. We expect that our work will lead to a new therapeutic approach for UM patients. Because half of UM patients will experience tumor metastasis, we must interfere with the metastatic process while treating the primary tumor. The neutralizing agents, oligonucleotide, have been widely studied and some have been approved by Food and Drug Administration for other diseases. Testing the use of them in UM animal models is a critical step in moving this approach to clinical trials. We expect that this research will result in a prototype drug within 5 years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210992
Entities
People
- Yu Liu
Organizations
- United States Army
- University of Houston