Enhancing the Efficacy of Precision Oncology-Based Therapy in Rhabdomyosarcoma
Abstract
My research proposal seeks to address the Fiscal Year 2020 Peer Reviewed Cancer Research Program (PRCRP) topic areas of pediatric, adolescent, young adult cancers as well as the PRCRP military health focus area of mission readiness. Rhabdomyosarcoma (RMS) is a devastating pediatric soft-tissue cancer. The survival rate for children suffering from RMS is poor. Current treatment options, including chemotherapy and radiation, have proven to be ineffective for patients at the advanced stage of this cancer and are shown to cause serious side effects and complications such as second cancers. There remains an urgent need to identify more effective therapy options for RMS. Based on a number of previous researches, multiple gene mutations, which are permanent alterations in DNA, have been identified in RMS cancer samples. However, whether these mutations play a key role in the growth of cancer cells is unknown. As several recent clinical trials have shown, treating certain cancer types based on the presence of specific mutations in individual cancer patients has yielded positive results in improving survival outcomes. Therefore, characterizing the effects of specific mutations on cancer growth in RMS will, in the same vein, inform better tailored treatment options. My proposed research aims to determine the functional consequences of specific gene mutations of cancer cell growth in RMS. Since there currently is no cost-effective mammalian RMS model for large-scale testing of gene mutations, we will use the zebrafish model, which mimics the features of the human disease and is amenable to large-scale and cost-effective experimental studies in order to characterize the biological effects of gene mutations on RMS cancer growth. In parallel, we will test the same mutations in human RMS cancers cells grown in a Petri dish. For the gene mutations that affect RMS cancer growth, we will also assess whether they affect how the cancer cells respond to the drugs that inhibit specific gene activities. Since only a subset of these mutations exhibit abnormal activity in RMS cancer cells, therapies that target these mutations will eliminate the cancer cells while leaving the normal cells intact, thereby producing no significant complications, in contrast to the damages in both cancerous and normal cells seen in patients treated with conventional treatments. Finally, by using an animal model for large-scale functional testing of gene mutations to identify the ones with biological relevance in RMS, our proposed research will facilitate the process of prioritizing drug therapy options based on the mutations present in each RMS patient and consequently improve the survival outcomes of RMS patients. For the military Service Members that have children with RMS, taking care of these children can exert substantial emotional, financial, and social tolls, incurred not only by the disease itself but also by the serious side effects or complications that conventional treatment options introduced. By identifying effective therapies that not only improve survival outcomes of RMS patients but also produce minimal side effects and complications, the proposed study will allow Service Members to continue on active duty and responsibilities, improve their quality of life, and alleviate their emotional and financial burdens.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110795
Entities
People
- Eleanor Chen
Organizations
- United States Army
- University of Washington