Jeffrey A Toretsky


Molecular Oncology Program Leader


Lombardi Comprehensive Cancer Center (LCCC)


Dr. Jeffrey Toretsky has been studying Ewing sarcoma since 1992. His early work investigated minimal residual disease, antisense oligonucleotide growth inhibition, and novel EWS-FLI1 targets and protein interactions. The Toretsky laboratory continues to focus on Ewing sarcoma, since the tumors contain a unique target, EWS-FLI1, which is not found in non-tumor cells. This unique target offers an opportunity to create new medicines that will more specifically eliminate tumor growth while sparing normal cells. In addition to being a unique cancer target, EWS-FLI1 has the biochemical properties of an intrinsically disordered protein (IDP).

Direct screening for small molecules that bind to EWS-FLI1 required recombinant protein along with surface plasmon resonance technology. Once a lead compound was identified, a network of collaborators in medicinal chemistry, biochemistry, structural biology, and pharmacology helped advance the molecule YK-4-279, as an inhibitor of EWS-FLI1, towards a clinical trial. In 2014, Dr. Toretsky co-founded Oncternal Therapeutics, Inc. which created TK216, an analog of YK-4-279, and has opened a Phase 1 clinical trial for patients with relapse Ewing sarcoma (

The oncologic process set in motion by EWS-FLI1 remains relatively cryptic despite the identification of many transcriptional targets. The Toretsky laboratory identified RNA Helicase A (RHA) as a partner of EWS-FLI1 in 2006, thus the effects of EWS-FLI1 upon RHA function as a helicase is a current topic of research. Most recently, the Toretsky laboratory has shown EWS-FLI1 is a significant regulator of mRNA splicing.

This combination of studying the biochemistry of EWS-FLI1 and its role as an oncogene has led our research to the world of intrinsically disordered proteins and a process called Phase Separation. Fortunately, Georgetown University has a world-recognized center, Institute for Soft Matter Synthesis and Metrology that has welcomed Dr. Toretsky as a member. (

Dr. Toretsky continues to practice as a pediatric hematologist/oncologist by co-directing a multidisciplinary sarcoma clinic at Children’s National Medical Center along with regular inpatient attending. In addition to Ewing sarcoma, his clinical interests include osteosarcoma (bone cancer), synovial sarcoma, rhabdomyosarcoma, and many other related tumors. He hopes to prescribe more effective and precisely targeted therapies for his patients in the future.