Ewing sarcoma is a cancer that mainly grows in the bones of children and teenagers. If found early, it can be cured with surgery, radiation and chemotherapy, however these treatments have serious side effects in young people, and are often ineffective. We propose to lay the groundwork for a new therapy that has less side effects, and could also be effective when the standard treatment fails. Our proposed strategy may achieve that by developing a drug that decreases the amount of a protein, EWS-FLI1 that is only produced by Ewing sarcoma cells, and essential for these cancer cells to grow and survive. We previously found that ERG, a protein very similar to the FLI1 part of EWS-FLI1, is stabil...

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Ewing sarcoma is a cancer that mainly grows in the bones of children and teenagers. If found early, it can be cured with surgery, radiation and chemotherapy, however these treatments have serious side effects in young people, and are often ineffective. We propose to lay the groundwork for a new therapy that has less side effects, and could also be effective when the standard treatment fails. Our proposed strategy may achieve that by developing a drug that decreases the amount of a protein, EWS-FLI1 that is only produced by Ewing sarcoma cells, and essential for these cancer cells to grow and survive. We previously found that ERG, a protein very similar to the FLI1 part of EWS-FLI1, is stabilized by an enzyme called USP9X, which can be blocked with a chemical compound (our drug candidate) resulting in rapid loss of ERG. We hypothesize that USP9X has the same function to stabilize EWS-FLI1, and therefore we expect that the chemical compound that blocks USP9X would also cause rapid loss of EWS-FLI1 in Ewing sarcoma cells. We have already obtained some preliminary results that support this hypothesis, and now plan to further study how USP9X affects EWS-FLI1 stability and test the effects of the chemical inhibitor in Ewing sarcoma cells grown in a dish and when implanted in mice to evaluate the therapeutic potential of our drug candidate.

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