Our Mission

The D-Feet Cancer Mission Statement

The mission of D-Feet Cancer The Dalton Fox Foundation is to help discover targeted therapies and treatments for Ewing Sarcoma, a pediatric bone cancer, through increased awareness and charitable funding.

The First D-Feet Cancer Beneficiary

All donations will directly benefit Ewing Sarcoma researchers. Our goal is to directly fund promising Ewing Sarcoma research, no matter where it occurs, and find a cure for this horrible disease. With only 4% of the billions of dollars our government spends annually on cancer research going to treating pediatric cancers, more funding and research is needed to cure Ewing Sarcoma and pediatric cancers in general.

The first recipient of funding from D-Feet Cancer is the Toretsky Lab at Georgetown University. Dr. Jeff Toretsky is a renowned Ewing Sarcoma researcher and practicing pediatric oncologist at Georgetown University in Washington D.C. He 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 focuses on influencing a protein, EWS-FLI1, only present in Ewing Sarcoma tumor cells. Researchers at the Toretsky lab created the first small molecule to directly target EWS-FLI1, YK-4-279, which is a useful laboratory probe. The drug made from YK-4-279, called TK216, is in Phase 2 clinical trials and sponsored by Oncternal Therapeutics, Inc Dr. Toretsky co-founded this drug company. Learn more about TK216.

A Message from Dr. Toretsky

The major focus of my laboratory is to evaluate the role of chromosomal breakpoint- generated fusion proteins in oncogenesis and tumor maintenance. My laboratory focuses on the Ewing’s sarcoma (ES), which contain pathognomonic EWS-ets fusion proteins. These fusion proteins are the ideal cancer target as they exist only in ES cells and their elimination in laboratory models is toxic to the tumors. The Toretsky Laboratory has developed novel therapies that are now implemented in the clinic to improve the survival of children with ES and reduce morbidity. While early results show some promise, too few patients benefit. Ongoing research in the laboratory includes trying to find out why some patient tumors regress and others appear resistant.

An ideal cancer therapeutic target is a molecule that is unique to the cancer cell. EWS-FLI1 is a unique protein that is only found in ES cells. Reduction of EWS-FLI1 leads to the death of ESFT cells. Therapy directed towards EWS-FLI1 might eliminate a repopulating stem cell and render chemotherapy more effective towards the cure of ES patients. In order to take advantage of the uniqueness of EWS-FLI1, my lab identifies protein partners of EWS-FLI1. The interaction points between these protein partners and EWS-FLI1 have the potential to be unique in three-dimensional space. These unique interaction points could then be targets for EWS-FLI1 inactivation.

Our laboratory utilizes recombinant EWS-FLI1 to directly screen small molecules as potential probes of EWS-FLI1 function. Small molecules that bind to EWS-FLI1 and inhibit EWS-FLI1 function are now in clinical trial as anti-tumor agents. High throughput screening of compound libraries will be initially conducted using surface plasmon resonance. These screening assays will directly measure the dissociation of full-length EWS-FLI1 from key protein partners.

The oncologic process set in motion by EWS-FLI1 remains relatively cryptic. Projects that elucidate the mechanism includes investigation of transcription, alternative splicing, helicase regulation, and histone alterations that modify chromatin access by transcription factors. Active collaborations include physicists, chemists, and informaticians to answer questions in a multidisciplinary fashion.

D-Feet Cancer, The Dalton Fox Foundation Initial Gift

Dalton’s family and friends, affectionately known as Team Dalton, donated over $30,000 to help him fight Ewing Sarcoma over the past year of his life. Shortly before Dalton died in May 2021, both of his parents, Will and Jen, promised D that they would not stop fighting on his behalf. With much help, Will and Jen created D-Feet Cancer to help find better treatments and a cure for Ewing Sarcoma.

The initial donation to D-Feet Cancer, in the amount of $30,000 is Team Dalton’s gift to Ewing Sarcoma research. Will and Jen chose Dr. Toretsky and his lab at Georgetown to receive D-Feet Cancer’s first grant primarily for his passion and success in researching Ewing Sarcoma. Additionally, Dr. Toretsky consulted on Dalton’s care with Dr. Pegram, Dr. File, and the fabulous local healthcare team at The Children’s Hospital of the King’s Daughters in Norfolk, Virginia. Dalton was also enrolled in the TK216 clinical trial during the late summer of 2020. Unfortunately, the new drug wasn’t successful in D’s case. Will and Jen are hopeful that Team Dalton’s gift will help Dr. Toretsky and his team further their research and help current and future Ewing Sarcoma patients beat this awful disease.

Dr. Toretsky’s Intent For The Initial Gift, In His Own Words

Many of the experiments that are performed in the Toretsky Laboratory require analysis in multiwell plates. This allows for up to 96 mini test tubes to run experiments in a single plate, with the completeness of testing conditions in triplicate, or more. To collect data from the 96 well plates, a device, called a plate reader, is required to detect light from a chemical reaction, detect color changes, or show fluorescence. A multiwell plate reader can now measure a wide range of signals, however the current plate reader in the Toretsky lab is over 10 years old and needing replacement. We are grateful to the D- Feet Cancer, the Dalton Fox Foundation for supporting this upgraded replacement to continue our experimental quest to cure Ewing Sarcoma.

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