Prevention and Treatment Strategies for Recessive Dystrophic Epidermolysis Bullosa-Associated Squamous Cell Carcinoma
Abstract
This proposal will address the Fiscal Year 2017 (FY17) Peer Reviewed Medical Research Program (PRMRP) topic area of Epidermolysis Bullosa (EB). Specifically, the FY17 PRMRP area of encouragement focused on squamous cell carcinoma (SCC) in patients with EB. EB is an often devastating skin disease caused by genetic mutation that disrupts structural components of the skin leading to extreme skin fragility and frequent trauma-induced wounds. These wounds are often hard to heal and in the case of patients with recessive dystrophic EB (RDEB) more often than not lead to skin cancers (SCC) that will very rapidly progress and cause death. New treatments or preventative measures are urgently needed for this disease. The first goal of our project proposal is based on previous work by us that has uncovered an unexpected cause of EB skin cancers, namely a biological process usually associated with the immune system called “APOBEC.” APOBEC is an enzyme that helps our immune system to attack bacteria and viruses in a normal situation but seems to go wrong in cancer by attacking the DNA of skin cells. This DNA damage leads to cancer-causing mutations. Our project will identify what causes APOBEC to go wrong in skin cells and will try to prevent DNA damage by using drugs that interfere with APOBEC activity. At the same time, we propose to identify new drugs that might prove useful for treating APOBEC in cancers. Our second goal is also based on previous work by us identifying that the skin wounds create an environment in an RDEB patient that helps the cancer to grow and attack areas of the body away from the skin (a process called metastasis). We have identified a molecule, called thrombospondin-1, which is greatly increased in RDEB patients, particularly RDEB patient skin cancers. We aim to understand more about how this molecule leads to deadly skin cancers. Ultimately, we aim to test treatment approaches that target thrombospondin-1 to stop RDEB skin cancers from spreading. Lastly, our previous work has identified a new experimental drug that may be able to treat RDEB patients with skin cancer. Very little is known about how this drug works in RDEB skin cancer, and our third and final aim will therefore try to understand how this drug works. By doing so, we will better understand RDEB skin cancer and we may also discover certain signs that will help identify those patients that will benefit from such a treatment and those patients that potentially will not.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810382
Entities
People
- Andrew P South
Organizations
- Thomas Jefferson University
- United States Army