Dissecting the Difference in the Pathogenesis and Immune Microenvironment of Pediatric and Adult Osteosarcoma
Abstract
Osteosarcoma is a type of bone cancer that usually occurs in teenagers (pediatric osteosarcoma) or in elderly adults (adult osteosarcoma). In pediatric osteosarcoma, the cancer typically starts in the long bones of the leg during a period of rapid growth. In adult osteosarcoma, the tumor forms in the axial skeleton. The axial skeleton is subject to lots of weight-bearing stress and, as people age, they may experience painless microfractures in the spine, ribs, pelvis, or neck bones. The differences observed in pediatric and adult osteosarcoma presentations hint at distinct biological drivers of the disease but very little is known about what causes osteosarcoma. Despite the observed clinical differences, pediatric and adult osteosarcoma are treated with the same types of traditional chemotherapy. Outcomes for all patients with osteosarcoma have not improved significantly over the last 40 years. There is a clear need to understand what drives pediatric and adult osteosarcoma to improve and expand treatment options for patients with this disease. This proposal focuses on the divergent biology and etiology of pediatric and adult osteosarcoma. We will investigate the different cellular programs found in osteosarcoma patient tumor samples from both adult (>60 years old) and pediatric (<21 years old) patients. We will utilize a novel sequencing technology that allows for interrogation of accessible regions of the genome (DNA) coupled with sequencing of active genes (RNA) within each cell of a sample. This information will allow us to understand what signals are driving tumor growth and how the immune system response is dampened by these signals. We will also utilize advanced imaging technology to further investigate tumor-immune cell interactions that lead to the cancer s ability to escape immune surveillance. With the discovery of the key cellular programs driving the subtypes of osteosarcoma, we may uncover new therapeutic targets for drug development and consider repurposing already approved targeted agents to improve outcomes for all patients with osteosarcoma. Clinical trials investigating the use of currently approved therapies that target identified pathways in osteosarcoma are possible within the next 5 years. For patients with this rare tumor type, the project will increase the understanding of the causes of osteosarcoma and may offer expanded treatment options. For patients with other types of rare cancers, successful application of this novel sequencing technique coupled with hypothesis-driven interrogation of the data will expand our ability to rigorously study cancers for which there are no clinically relevant model systems. Additionally, discovery of the drivers of osteosarcoma may parallel the beginnings of other sarcoma subtypes, increasing our understanding of rare cancers more broadly.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310610
Entities
People
- Erica Pimenta
Organizations
- Dana–Farber Cancer Institute
- United States Army