Ewing Sarcoma

The patient received the first cycle of the chemotherapy regimen of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VAC/IE) and was discharged in a stable condition. This case emphasizes the need to consider EES in the differential diagnosis of nasal masses and highlights the necessity of molecular testing for EWSR1 rearrangements to confirm the diagnosis and guide therapy. Increased awareness and reporting are vital to enhancing diagnosis and management of this rare entity.

Collectively, these findings demonstrate that distinct miRNA profiles can differentiate pediatric sarcoma types and subtypes and offer clinically relevant insights into tumor biology, prognosis, and potential diagnostic application.

P1, N=171, Recruiting, SEED Therapeutics, Inc. | Not yet recruiting --> Recruiting

Although the activity of single-agent checkpoint inhibitors remains disappointing in pediatric bone tumors, rational tyrosine kinase inhibitor-chemotherapy combinations, improved biologic risk stratification (ctDNA; MYC in OS; STAG2 in ES), recycling chemotherapeutic agents, and standardized local-control frameworks are being developed to reshape care. Near-term priorities include biomarker-anchored upfront trials and supportive-care measures that preserve cure while reducing late effects. Clinical trials provide access to potentially paradigm-shifting therapeutic strategies.

As a result, we identified Torin 2, talazoparib, and trabectedin as top 3 candidates with potent anti-Ewing sarcoma activity. Mechanistically, exogenous TGF-β1 was sufficient to induce resistance in tumor-only spheroids, whereas pharmacological inhibition of TGF-β1 signaling restored drug sensitivity in heterotypic spheroids. These findings establish the DCMiC platform as a low-cost, physiologically relevant system for modeling tumor-stroma interactions and enabling scalable drug discovery in clinically relevant contexts for Ewing sarcoma and other solid tumors.

These findings underscore the need for continued collaboration to standardize diagnostic approaches across Latin America, aiming to improve treatment outcomes for ES patients.

Furthermore, we demonstrate that combined inhibition of these factors with MSC778 induces synergistic killing of cancer cells. Together these data highlight FEN1 inhibition as an attractive precision oncology strategy either as monotherapy or as a combination therapy with a broad range of current and next generation DDR-targeting agents.

We present the case of a 42-year-old female with recurrent ES with pulmonary metastases who, after progressing on anti-IGF-1R monotherapy with figitumumab (CP-751,871, NCT00560235), achieved complete remission in a phase I clinical trial (NCT00976508) that combined figitumumab IGF-1R-inhibition with growth hormone receptor antagonist pegvisomant. The impressive response observed highlights the clinical synergy of this combination which warrants further clinical exploration as well as the potential of IGF-1R inhibition for ES. Additionally, this case suggests that targeted therapy discontinuation might be an option for select patients with long-term complete remission.

P2/3, N=437, Active, not recruiting, Children's Oncology Group | Recruiting --> Active, not recruiting | Initiation date: Jul 2026 --> Nov 2025

P1/2, N=90, Recruiting, St. Jude Children's Research Hospital | Active, not recruiting --> Recruiting | N=46 --> 90

This case highlights the diagnostic complexities of round cell sarcoma of bone, which can mimic other benign bone lesions. It underscores the importance of multidisciplinary evaluation, genetic testing, and timely oncological intervention to improve patient outcomes.

Next-Generation Sequencing (NGS) revealed EWSR1::FLI1 rearrangement in all three tested PCES cases (100%). In conclusion, the accurate diagnosis of PCES requires a comprehensive approach, integrating detailed morphologic assessment with immunohistochemical studies and potentially cytogenetics/molecular assays.