Revealing and Targeting Lipidomic Vulnerabilities to Treat Metastatic Melanoma
Abstract
The major reason melanoma causes death in patients is because melanoma cells can travel to lymph nodes or into the blood to spread to organs (e.g., lung, liver) and cause organ failure. However, the harsh blood environment kills most melanoma cells during cancer progression. Only melanoma cells that have specific changes that protect them against cellular stress in the blood survive to form cancer in organs. Our lab recently made a breakthrough discovery that melanoma cells in lymph nodes acquire a fatty acid (oleic acid) that protects them from cellular stress. We believe melanoma cells can undergo many more different kinds of lipid changes in lymph nodes that shield them from cellular stress in the blood and allow them to survive. These changes remain to be discovered. The goal of our proposal is to study the lipid changes in melanoma cells in lymph nodes that protect melanoma cells from cellular stress. Then our lab will work to block these changes to prevent melanoma cells from spreading to distant organs. If we can identify the lipid changes that protect melanoma cells and prevent those changes from occurring, we will be able to develop new treatments for early-stage melanoma in patients. Cancer cells from lymphatics have been largely ignored because it is difficult to isolate cancer cells from lymphatics. Our laboratory has developed innovative approaches to isolate melanoma cells from lymph and to conduct extensive lipid analyses on these cells, which has previously been impossible to do. We propose to use these new, highly innovative techniques and tools to study the lipid changes in melanoma cells in lymph nodes to identify which changes allow the melanoma cells to spread from lymph nodes to organs. Our proposal addresses the fiscal year 2022 (FY22) Melanoma Research Program (MRP) Challenge Statement, as it redefines prevention to include impending the initiation and progression of primary melanoma earlier in the disease cycle at the point of melanoma spread to lymph nodes. We will focus our research studies on eliminating lymph node progression of cutaneous and rare nodular melanomas using melanomas from patient surgical samples. Our proposal addresses several of the key FY22 MRP Focus Areas. Our work will identify methods to decrease risk of melanoma development beyond sunscreen and protective clothing, as success in our project will lead to prevention of melanoma progression by targeting melanoma spread from lymph nodes to organs. We will determine how manipulating the lipids in the lymph node will impact melanoma cell spread to organs, thus identifying how the tumor microenvironment…impacts tumor progression. We will conduct comprehensive lipid analyses of melanoma cells from the initial tumor and from lymph nodes of patients to identify lipid changes that occur in melanoma cells in the lymph node. We will test if targeting these changes can stop melanoma cells from spreading to and from lymph nodes, thereby, understanding mechanisms that underlie metastatic spread to…nodal sites. Success in our line of investigation will advance the field of melanoma research and patient care and contribute to immediate identification and understanding of risk factor determinants for melanoma metastasis. By identifying lipid factors that cause melanoma cells to spread from lymph nodes to other organs, we should be able to predict patients that are more likely to benefit from therapies targeting the lymph node or find ways to make current therapies work better for patients who might harbor cancer cells in their lymph nodes. We believe this proposal has impactful clinical application and benefit because by developing new approaches to understanding melanoma spread to lymph nodes, we will lay a foundation to accurately identify and help patients with melanoma detected in their lymph nodes who are likely to have progression to distant metastasis and to treat these patients before metastasis oc
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310765
Entities
People
- Jessalyn Ubellacker
Organizations
- President and Fellows of Harvard College
- United States Army