Grants - V Scholar Grants - Minnesota - 2015

Branden Moriarity, Ph.D.

Funded by the Dick Vitale Gala in memory of Dillon Simmons

Cancer is a disease genetic in origin and a major cancer causing gene is MYC. Many human cancers, including pediatric sarcomas such as osteosarcoma, rhabdomyosarcoma, Ewing’s, and synovial sarcoma, are driven by MYC. It has been argued a major leap towards finding a cure for these cancers will be the development of therapies that target MYC. Unfortunately, MYC has been notoriously challenging to target therapeutically. We have recently found a new regulator of MYC called PVT1. We demonstrated PVT1 helps sustain MYC at elevated levels in adult cancer cells, and when PVT1 is removed MYC returns to levels seen in non-cancer cells. This reduction in MYC drastically reduces the cancerous potential of these cells. Thus, the purpose of this work is to investigate this phenomenon in pediatric sarcomas. We have preliminary demonstrating this interaction indeed occurs in pediatric osteosarcoma cancer cells and removing PVT1 leads to reduced MYC levels; which we previously demonstrated leads to diminishes growth and viability of cancer cells. Accordingly, this work will investigate if this phenomenon occurs in many pediatric sarcomas and develop a therapeutic approach to inhibit PVT1 in pediatric cancer patient tumors, leading to loss of MYC and regression of tumors. This would be a breakthrough for the treatment of pediatric sarcoma as this disease has seen little to no advances in targeted therapy over the last several decades. If an effective therapeutic is developed, a clinical trial using this therapeutic approach will be carried out in pediatric sarcoma patients in the future.