Compositions and methods for identification assessment, prevention, and treatment of Ewing sarcoma using TP53 dependency biomarkers and modulators
AssigneeDana-Farber Cancer Institute, Inc.
InventorKimberly Stegmaier
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Abstract
The present invention is based, in part, on the identification of TP53 dependency biomarkers, including MDM2, MDM4, USP7, and Wip1/PPM1D, as well as modulators and methods of use thereof, for identifying, assessing, preventing, and treating Ewing sarcoma.
Claims18
A method of treating a subject afflicted with Ewing sarcoma, wherein cancer cells of the Ewing sarcoma encode intact tumor-suppressor 53 (p53), comprising administering to the subject i) a mouse double minute 2 (MDM2) inhibitor, wherein the MDM2 inhibitor is ATSP-7041, and ii) a ubiquitin specific peptidase 7 (USP7) inhibitor or a protein phosphatase, Mg2+/Mn2+-dependent 1D (PPM1D) inhibitor, wherein the USP7 inhibitor is P5091 or the PPM1D inhibitor is GSK2830371, thereby treating the subject afflicted with Ewing sarcoma.
A method of inhibiting hyperproliferative growth of Ewing sarcoma cancer cells, wherein the Ewing sarcoma cancer cells encode intact tumor-suppressor 53 (p53), comprising contacting the Ewing sarcoma cancer cells with i) a mouse double minute 2 (MDM2) inhibitor, wherein the MDM2 inhibitor is ATSP-7041, and ii) a ubiquitin specific peptidase 7 (USP7) inhibitor or a protein phosphatase, Mg2+/Mn2+-dependent 1D (PPM1D) inhibitor, wherein the USP7 inhibitor is P5091 or the PPM1D inhibitor is GSK2830371, thereby inhibiting hyperproliferative growth of the Ewing sarcoma cancer cells.
Dependencies are inferred from the claim text.