Childhood cancer arises from disrupted developmental processes driven by genetic and epigenetic changes, making them fundamentally different from adult malignancies. Understanding this unique biology requires models that faithfully capture the complexity of pediatric cancer. Patient-derived organoids (PDOs) have emerged as a transformative tool in this space, preserving the heterogeneity, plasticity and microenvironmental features of the [...]

Smith KH, Trovillion EM, McKinney KQ, Gourabathini P, Wells K, Gandra D, Sholler C, Votruba I, Oesterheld J, Saulnier Sholler GL. In Vitro and In Vivo Efficacy of Romidepsin Alone and in Addition to Standard of Care for Treatment of Ewing Sarcoma. Cancers (Basel). 2025 Dec 17;17(24):4018. doi: 10.3390/cancers17244018. PMID: 41463266; PMCID: PMC12730613. In Vitro and [...]

Osteosarcoma is the most common type of primary malignant bone tumor in children, adolescents and young adults and remains a significant clinical challenge, especially in the context of metastatic disease. Here we report the case of a 9-year-old female with refractory metastatic osteoblastic osteosarcoma with disease progression in the lungs following neoadjuvant chemotherapy, local control [...]

Approved treatments for patients with refractory and/or relapsed (R/R) high-risk (HR) neuroblastoma are limited, and there is a need for new treatment combinations. In this case series, 4 patients were treated with the anti-GD2 monoclonal antibody naxitamab and granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with cyclophosphamide and topotecan between August 2021 and December 2022. This [...]

Neuroblastoma is a common childhood malignancy, and high-risk presentations, including an MYCN amplified status, continue to result in poor survival. Difluoromethylornithine (DFMO) is a new and well-tolerated treatment for high-risk neuroblastoma. This review article discusses preclinical and clinical data that resulted in the establishment of DFMO as a treatment for neuroblastoma. The review of preclinical [...]

There has been little improvement in Ewing sarcoma survival rates over the past several decades and new therapeutic options are desperately needed. Histone deacetylases (HDACs) are known to play a role in cancer development and progression. We show that HDAC2 is overexpressed in Ewing sarcoma cells and that an HDAC inhibitor, Panobinostat, is cytotoxic to [...]

Most high-risk neuroblastoma patients who relapse succumb to disease despite the existing therapy. We recently reported increased event-free and overall survival in neuroblastoma patients receiving difluoromethylornithine (DFMO) during maintenance therapy. The effect of DFMO on cellular processes associated with neuroblastoma tumorigenesis needs further elucidation. Previous studies have shown cytotoxicity with IC50 values >5–15 mM, these doses [...]

A total of 186 eligible patients were enrolled with 144 evaluable for safety and 124 evaluable for response. The average number of days from biopsy to initiation of the MTB‑recommended combination therapy was 38 days. Patient benefit was exhibited in 65% of all subjects, 67% of neuroblastoma subjects, 73% of CNS tumor subjects, and 60% [...]

High risk neuroblastoma (HRNB) accounts for 15% of all pediatric cancer deaths. Despite aggressive therapy approximately half of patients will relapse, typically with only transient responses to second-line therapy. This study evaluated the ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) as maintenance therapy to prevent relapse following completion of standard therapy (Stratum 1) or after salvage therapy [...]

Eslin D, Zage PE, Bergendahl G, Lewis E, Roberts W, Kraveka J, Mitchell D, Isakoff MS, Rawwas J, Wada RK, Fluchel M, Brown VI, Ginn K, Higgins T, BeeravallyNagulapally A, Dykema K, Hanna G, Ferguson W, Saulnier Sholler GL. A phase II trial of nifurtimox combined with topotecan and cyclophosphamide for refractory or relapsed neuroblastoma and [...]