Exploiting Stress Dependencies in Ewing Sarcoma
Ewing sarcoma is the second most common bone cancer in children and young adults, with 5-year survival rates of only 15-30% for metastatic and relapsed patients. Despite aggressive multimodal treatment, current therapies fail to effectively target the EWSR1::FLI1 fusion protein that drives up to 90% of cases. A major untapped opportunity lies in the cellular stress pathways this fusion oncogene exploits for tumor survival. We are targeting endoplasmic reticulum stress and the unfolded protein response to develop a new class of therapies for this devastating disease.
Our Discoveries
Findings in our lab are making a difference to the understanding and treatment of Ewing sarcoma. Our work has led to the following discoveries:
Targeting STAG2-mutant Ewing sarcoma cells with novel compounds
Selective inhibition of STAG2-mutant Ewing sarcoma cells reveals exploitable cohesin complex vulnerabilities for precision therapy
Exploiting ER stress as a therapeutic vulnerability in Ewing sarcoma
Activation of endoplasmic reticulum stress and unfolded protein response selectively induces cell death in Ewing sarcoma cells.
StagX1 selectively targets CES1-positive Ewing sarcoma cells
CES1 expression defines a molecular vulnerability that enables selective targeting of Ewing sarcoma cells with the isoquinolinone compound StagX1.
Help us turn fundamental biology into the next breakthrough cancer treatment
