The Impact of the Intestinal Microbiome on Sarcoma Metastasis
The leading cause of death among children diagnosed with bone tumors is metastasis, or the spread of the tumor from its initial location to other places in the body. Decades of clinical trials aimed at making chemotherapy stronger or more intense have not improved the survival of children who are diagnosed with a metastatic bone tumor nor of children who suffer a metastatic relapse. The impact of the organisms living in a patient’s intestinal tract on the progression of adult cancers is being intensively studied, but there have been no such studies in children. In our mouse models, we found that altering the bacteria and fungi living in the intestinal tract of mice with bone cancer can cause the tumors to metastasize more aggressively. We found changes in the gene expression patterns in these tumors and changes in how cells from the immune system infiltrate into the tumors. It is not yet clear which of these changes is most important for making the tumors behave more aggressively, but understanding how this works will allow us to develop new approaches to the treatment of children with metastatic bone tumors.
Project Goal:
We have three main goals with this project. First, we want to make sure that our initial observations hold up when testing multiple different bone tumors to be sure that this is a general characteristic of all bone tumors. Second, we want to comprehensively analyze the alterations we are causing in the microorganisms living in the intestines of the mice. We also want to more carefully evaluate how these changes are associated with changes in the behavior of the tumors at the genetic level and how they are associated with changes in how the immune system interacts with the tumors. Finally, if we are to translate our findings from mice into human patients, we need to understand the composition of the microorganisms in the intestinal tracts of children with bone tumors, how they compare with children who do not have cancer, and how the microorganisms in the intestines of children with cancer change over time during treatment. We will accomplish this by analyzing stool collected from cancer patients at diagnosis and at set times during treatment as well as from healthy children without cancer. This valuable background information will allow us to apply what we learn in mice to human patients and help us design novel clinical trials aimed at applying our novel observations to improve the survival of children with metastatic bone cancer.
