EWS Collateral Sensitivity

The evolution of chemotherapeutic resistance can cause treatment failure in patients with Ewings sarcoma (EWS), a rare pediatric bone cancer that has no standardized second-line chemotherapy for patients with recurrent or treatment-resistant tumors. As resistance to the first-line therapy evolves, there is potential for the tumor to develop sensitivities to other chemotherapeutic agents besides the active treatment. This concept is known as collateral sensitivity, and it presents an opportunity for medical providers to plan more effective treatment regimens. However, it can be difficult to predict due to the stochastic nature of evolution. By analyzing gene expression patterns among many independent populations of an EWS cell line that have repeatedly evolved collateral responses, we aim to extract a collection of gene expression signatures that will predict states of collateral sensitivity against various existing chemotherapies.