Abstract
Rhabdomyosarcoma is the most common soft tissue sarcoma diagnosed in children and adolescents. Patients that are diagnosed with advanced or relapsed disease have exceptionally poor outcomes. The Children’s Oncology Group (COG) convened a rhabdomyosarcoma new agent task force in 2020 to systematically evaluate novel agents for inclusion in phase 2 or phase 3 clinical trials for patients diagnosed with rhabdomyosarcoma, following a similar effort for Ewing sarcoma. The task force was comprised of clinicians and basic scientists who collectively identified new agents for evaluation and prioritization in clinical trial testing. Here, we report the work of the task force including the framework upon which the decisions were rendered and review the top classes of agents that were discussed. Representative agents include poly-ADP-ribose polymerase (PARP) inhibitors in combination with cytotoxic agents, mitogen-activated protein kinase (MEK) inhibitors in combination with type 1 insulin-like growth factor receptor (IGFR1) inhibitors, histone deacetylase (HDAC) inhibitors, and novel cytotoxic agents.
Highlights
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents, with approximately 350 children diagnosed annually in the United States [1].Historically, the two main subtypes of RMS were classified by histologic characteristics and designated as alveolar RMS (ARMS) and embryonal RMS (ERMS) [2,3]
Pathway, which has been shown to be involved in both fusionpositive RMS (FP-RMS) and fusion-negative RMS (FN-RMS) oncogenesis
Entinostat was administered daily at dose of 4 mg/kg for 21 days [78,80]. This dosing schedule led to decreased growth of FN-RMS and FP-RMS tumors in mice, and in FP-RMS PDX models the combination of entinostat with vincristine was more effective than either agent alone [78]
Summary
Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
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