Investigating the effects of PAK4 as therapeutic targets for Ewing Sarcoma
Mentor Name: Jason Yustein
Doxorubicin and vincristine are commonly used in chemotherapy protocols designed for Ewing sarcoma patients: doxorubicin works by disrupting DNA replication and RNA transcription, while vincristine interferes with the formation of microtubules. Previous research has shown that two drugs working together are more effective in killing cancer cells than either of them individually. Currently, these two drugs are being used in combination with one another, yet despite these advancements there is still a risk for relapse after initial diagnosis. Through this project, the effects of these drugs combined with the effects of PAK4 inhibition will be investigated, potentially offering insight into the challenges currently associated with Ewing sarcoma treatment. The project will explore the metastatic mechanisms of Ewing Sarcoma as well as the effects of knocking out the PAK4 gene in Ewing Sarcoma cell models using a variety of methods to investigate (1) the effect of PAK4 on cell line models, (2) the effectiveness of potential pharmacological treatments, and (3) subsequent tumor and metastatic mechanisms in vivo. By culturing TC71 and A673 Ewing sarcoma cells obtained from in vivo lung tumors models, we can investigate the mechanisms of Ewing sarcoma metastasis. These cell cultures will provide insight for the effect of targeting PAK4 in tumors by using methods that model the metastatic properties of Ewing sarcoma cells, comparing them with their counterparts with PAK4 knock out.
