Identifying the Mechanism of Action of YW-155 against Survivin in Synovial Carcinoma

Background

Synovial sarcoma is a deadly soft-tissue malignancy with a predilection for adolescents and young adults. The tumor is associated in most cases with one of the SS18-SSX fusion oncogenes resulting from the characteristic t(X; 18) balanced chromosomal translocation. In recent years, YM-155 has been increasingly used as an anti-cancer agent, due to its inhibitory effect on survivin, a member of the inhibitor of apoptosis gene family. Survivin is absent in most terminally differentiated tissues, and its expression in tumors is associated with a more aggressive phenotype, shorter survival time, and decreased response to chemotherapy. YM-155 has recently been reported to block the expression of survivin via inhibition of the survivin promoter. However, recent data questions that this is the sole and main effect of this drug, which is already being tested in ongoing clinical studies.

Project Goal

Mike will work to conduct research that will revolve around understanding how the drug works in synovial sarcoma. They believe that the compound may function upstream of survivin and not necessarily at the promoter or via Caspase 8, as shown in leukemia. To test this hypothesis, they will examine relative protein abundance upstream of survivin. They hope that this will help gain a better understanding of treatment of synovial sarcomas.