Dr. Prachi Kothari Research Project as the 2019 Kristen Ann Carr Medical Oncology Fellow
Tumor profiling is often done by studying a sample of tumor tissue. As biopsies are invasive and often risky in patients who are severely ill, obtaining a blood sample to determine this same molecular information would be beneficial. The development of noninvasive molecular profiling strategies is essential for guiding targeted therapies and assessing response or relapse. It has been proven that a tumor can shed fragments of DNA, circulating tumor DNA (ctDNA), into a person’s circulation.
The objective of our investigation is to determine the feasibility of evaluating ctDNA in pediatric patients with solid tumors such as neuroblastoma, wilms tumor, and osteosarcoma. Its potential to be applied in the pediatric cancer setting is highly dependent on the genetic landscapes in the particular pediatric cancers in question. By studying the molecular profiles of tumor tissue in these different pediatric cancers, we are trying to understand concordance of mutations noted in the ctDNA at the same time point. With longitudinal sampling, we are gaining understanding on tumor heterogeneity and clonal evolution. We are also working on optimizing methods of collection, processing, and sequencing of cell-free DNA from plasma as well as urine samples from pediatric patients at different time points throughout treatment. Our project’s goal is to develop a powerful approach that will not only provide more efficient noninvasive molecular profiling, but will also provide a platform for studying response to therapy and resistance mechanisms in a variety of pediatric cancers.