Inflammatory Cell Death in Uveal Melanoma
Abstract
Melanoma of the eye occurs in the uveal tract (composed of the choroid, ciliary body and the iris) and is referred to as uveal melanoma (UM). UM is the most common malignancy of the eye in adults and accounts for 5% of all melanomas, with approximately 2,000 adults diagnosed every year. Some UM is associated with an ultraviolet-A (UVA) mutational signature. The high-level exposure of our military personnel to UV radiation increases their risk of melanoma compared to the general population; hence, our work is directly relevant to active-duty Service Members, Veterans, and other military beneficiaries. UM is a highly aggressive cancer; however, little is known about the causes and factors that contribute to disease progression. Half of UM patients develop advanced stage disease (metastasis) within 15 years of diagnosis, typically in the liver. UM that spreads through the body (metastasizes) to the liver is invariably fatal. Despite recent breakthroughs in skin melanoma, there are no Food and Drug Administration-approved targeted therapies for UM to date. Importantly, UM frequently do not respond to immune checkpoint therapies such as Yervoy plus either Keytruda or Opdivo. The goal of this application is to identify ways to attract immune cells to UM and, thus, make UM more responsive to immune therapies. The potential clinical benefit is the development of new, improved treatment options for UM patients. Our proposed research is complemented by the clinical strengths in UM at the Wills Eye Hospital and Thomas Jefferson University, especially in liver-directed therapies for metastatic disease. We have access to unique UM resources, large patient populations, and a strong collaborative network, which will all help us successfully complete the proposed studies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110958
Entities
People
- Andrew E Aplin
Organizations
- Thomas Jefferson University
- United States Army