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.
Watch this short animation, which highlights our exciting discovery that medulloblastoma cancer cells can spread through the blood, driven by the protein CCL2.
Help us advance the next generation of targeted cancer therapies.
