2. Academic Validation
  3. Non-chemotherapy adjuvant agents in TP53 mutant Ewing sarcoma

Non-chemotherapy adjuvant agents in TP53 mutant Ewing sarcoma

  • Sci Rep. 2023 Sep 1;13(1):14360. doi: 10.1038/s41598-023-40751-z.
Jin-Ah Kim 1,  Kenneth A Crawford 2,  Piero A Spada 2,  Leah R Martin 2,  Jiaqi Zhang 2,  Rain Wong 2,  Joel M Reid 3,  Clinton F Stewart 4,  Timothy M Frank 2,  Qianqian Liu 5,  Joel E Michalek 5,  Charles Keller 6
Affiliations

Affiliations

  • 1 Children's Cancer Therapy Development Institute, 9025 NE Von Neumann Drive Ste 110, Hillsboro, OR, 97006, USA. [email protected].
  • 2 Children's Cancer Therapy Development Institute, 9025 NE Von Neumann Drive Ste 110, Hillsboro, OR, 97006, USA.
  • 3 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
  • 4 Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, 38105-2794, USA.
  • 5 Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio, TX, 78229, USA.
  • 6 Children's Cancer Therapy Development Institute, 9025 NE Von Neumann Drive Ste 110, Hillsboro, OR, 97006, USA. [email protected].
PMID: 37658148 DOI: 10.1038/s41598-023-40751-z
Abstract

Ewing sarcoma (EWS) is a malignant tumor arising in bone or soft tissue that occurs in adolescent and young adult patients as well as adults later in life. Although non-metastatic EWS is typically responsive to treatment when newly diagnosed, relapsed cases have an unmet need for which no standard treatment approach exists. Recent phase III clinical trials for EWS comparing 7 vs 5 chemotherapy drugs have failed to improve survival. To extend the durability of remission for EWS, we investigated 3 non-chemotherapy adjuvant therapy drug candidates to be combined with chemotherapy. The efficacy of these adjuvant drugs was investigated via anchorage-dependent growth assays, anchorage-independent soft-agar colony formation assays and EWS xenograft mouse models. Enoxacin and entinostat were the most effective adjuvant drug in both long-term in vitro and in vivo adjuvant studies. In the context that enoxacin is an FDA-approved Antibiotic, and that entinostat is an investigational agent not yet FDA-approved, we propose enoxacin as an adjuvant drug for further preclinical and clinical investigation in EWS patients.

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