Metabolic Liabilities and Hematopoietic Fate Decisions in PIK3CA/KDR Co-Mutant Angiosarcoma
Abstract
Angiosarcoma is a rare and aggressive type of cancer that has poor outcomes. Our research aims to understand this cancer better and find ways to treat it more effectively. We focus on studying how specific changes in the genes of angiosarcoma cells affect their metabolism, which is how they get energy and grow. By understanding these changes, we hope to develop new treatments that target the metabolic changes in angiosarcoma cells. Currently, there is not enough information about the genetic causes of angiosarcoma, and it is difficult to study how these genes, metabolism, and cell behavior are related. We also lack good models to mimic angiosarcoma in the laboratory, which makes it harder to understand how the cancer works. For this project, we will test our scientific hypothesis that metabolic pathways are perturbed in angiosarcomas harboring PIK3CA/KDR co-mutations, and they govern hematoendothelial progenitors to develop vascular malignancy. Our project has two main goals. First, we aim to investigate how specific genetic changes in angiosarcoma cells impact their metabolism, leading to abnormal growth. Second, we intend to develop new disease models to test this concept, thereby facilitating the advancement of targeted treatments that can specifically address the metabolic alterations in angiosarcoma cells. This research addresses the Fiscal Year 2022 Rare Cancer Research Program s Focus Areas Biology and Etiology and Research Model. The ultimate goal of our research is to make a meaningful impact on the lives of patients with angiosarcoma. By uncovering the metabolic vulnerabilities associated with specific genetic mutations in angiosarcoma, we aim to develop targeted treatments that can effectively inhibit the growth and progression of the cancer. Our findings will contribute to a better understanding of angiosarcoma, leading to the development of personalized treatment strategies tailored to the unique characteristics of this cancer. While the direct clinical application of our research may take time, the insights gained from our study will have important implications for rare cancer research as a whole. By delving into the relationship between genetic mutations, metabolic processes, and cell fate decisions in angiosarcoma, we will generate valuable knowledge that can be applied to other rare cancers with similar underlying mechanisms. This will help fill the existing gap in research resources for rare cancers and provide a foundation for future studies in this field. Our research involves the use of advanced gene editing techniques and stem cells to create a model of angiosarcoma. Through this modeling system, we will investigate how genetic mutations impact the metabolic pathways and gene expressions within the cells. By utilizing gene engineering technology, we can precisely modify specific genes associated with angiosarcoma. These modifications will allow us to understand the effects of these mutations on the metabolic behavior of the cells and identify new molecules that control tumor metabolism. The interdisciplinary nature of our project, combining biology, genetics, and computational analysis, will lead to the generation of comprehensive omics data for angiosarcoma. This extensive dataset will contribute to the establishment of a preclinical modeling platform that can be used to further explore the genetic features, metabolic pathways, and molecular programs in angiosarcoma and other rare cancers. Such platforms are critical for the development of effective treatment strategies and the evaluation of potential therapeutic targets. In summary, our research aims to uncover the metabolic vulnerabilities of angiosarcoma and explore their potential as targets for therapy. By advancing our understanding of this rare cancer, we hope to improve outcomes for patients and make significant contributions to the field of rare cancer research. Through our work, we aspire to develop personaliz
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310905
Entities
People
- Jong Hyuk Kim
Organizations
- United States Army
- University of Florida