TS-005604 — This new process of treating fusion-driven pediatric sarcomas centers around the nuclear receptor NR0B1, which has the ability to impede and suppress the response of other nuclear receptors to their natural ligands. Currently there are no targeted therapies approved for fusion-driven pediatric sarcomas, establishing what is likely the first demonstration that disrupting NR0B1 can unmask nuclear receptor–dependent therapeutic responses in a pediatric cancer, offering a novel and potentially safer treatment approach for fusion‑driven sarcomas.

TS-000856 — Alveolar Rhabdomyosarcoma is a malignancy that forms in a muscle, stemming from a soft tissue and residing in the lungs. A team of researchers led by Dr. Benjamin Stanton have developed an initial characterization of PAX3-FOXO1 that is localized across the genome associated with this disease. PAX3-FOXO1 localizes to both repressed and active regions of the tumor genome and is initially targeted as a driver oncogene. Additionally, the immediate-early targets of localization encode metabolic genes and cell cycle genes. By understanding this rare tumor oncogene, caregivers will be able to identify target genes and implement FDA-approved therapies.

TS-000506 — We have targeted core catalytic subunits of ATP-dependent chromatin remodeling complexes in each major subtype of rhabdomyosarcoma with PROTAC degraders (SMARCA4-31, DL-dS2-4) to enable concomitant degradation of (1) the driver oncogene in the alveolar subtype, PAX3-FOXO1, and (2) the FOXO1 transcription factor in the embryonal subtype. These effects are accompanied by defects in rhabdomyosarcoma cell proliferation. The degradation of PAX3-FOXO1 is only partially rescued with removal of the PROTACS. To our knowledge, FOXO1 or PAX3-FOXO1 fusions have not been targeted for rapid degradation previously. This is a (1) new process of BAF-proximity degradation, and (2) a new process of PAX3-FOXO1 degradation. We are not aware of other methods of targeted degradation of FOXO1 or PAX3-FOXO1 in rhabdomyosarcoma, or other tumors.