Children's Cancer Therapy Development Institute, 9025 NE Von Neumann Drive Ste 110, Hillsboro, OR, 97006, USA.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
Sci Rep. 2023 Sep 1;13(1):14360. doi: 10.1038/s41598-023-40751-z.
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.
尤因肉瘤（EWS）是一种起源于骨骼或软组织的恶性肿瘤，发生于青少年和年轻成年患者以及生命后期的成年人。虽然新诊断的非转移性 EWS 通常对治疗有反应，但复发病例的需求尚未得到满足，目前尚无标准的治疗方法。最近针对 EWS 的 III 期临床试验比较了 7 种与 5 种化疗药物，未能提高生存率。为了延长 EWS 缓解的持久性，我们研究了 3 种非化疗辅助治疗药物候选物，以与化疗联合使用。通过锚定依赖性生长测定、锚定非依赖性软琼脂集落形成测定和 EWS 异种移植小鼠模型研究了这些辅助药物的疗效。依诺沙星和恩替诺特在长期的体外和体内辅助研究中是最有效的辅助药物。鉴于依诺沙星是一种获得 FDA 批准的抗生素，而恩替诺特是一种尚未获得 FDA 批准的研究性药物，我们建议依诺沙星作为 EWS 患者进一步的临床前和临床研究的辅助药物。
