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Ewing sarcoma: investigational mono- and combination therapies in clinical trials
Jessica Gartrell1, Carlos Rodriguez-Galindo1,2
1Department of Oncology, St. Jude Children's Research Hospital, Memphis, United States of America.
Introduction:
Over the last decades, multi-institutional clinical trials have resulted in significant improvements in the outcomes of patients with localized Ewing sarcoma; however, those with metastatic and recurrent diseases continue to fare poorly. More recently, advancements made in understanding the biology of the disease and mechanisms of response to therapy have opened the door for the incorporation of targeted therapies. Here we review the current state of treatment for Ewing sarcoma and the most recent preclinical advancements that have the potential to translate to improved care.
Areas Covered:
This review provides a general overview of the most recent clinical trials completed in Ewing sarcoma, as well as the preclinical and translational data that has the potential to be incorporated into clinical trials. A PubMed review as well as a review of published meeting abstracts was used to compose this review.
Expert Opinion:
While dose-intenstifying strategies have failed to lead to improvements in outcomes for patients with the highest-risk disease, recent preclinical advancements have shed light on potential new targeted strategies. The lack of early-phase clinical trial responses should not deter us from further developing these agents, but instead should guide us in designing novel combination strategies.
Insights
While localized Ewing sarcoma outcomes have improved, metastatic and recurrent cases remain challenging. New targeted therapies show promise for improving care, guiding future treatment strategies.
Area of Science:
- Pediatric Oncology
- Sarcoma Research
- Translational Medicine
Background:
- Multi-institutional trials improved localized Ewing sarcoma outcomes.
- Metastatic and recurrent Ewing sarcoma patients still have poor prognoses.
- Understanding disease biology fuels targeted therapy development.
Purpose of the Study:
- Review current Ewing sarcoma treatments.
- Highlight recent preclinical advancements.
- Identify potential clinical trial candidates.
Main Methods:
- Literature review of PubMed and meeting abstracts.
- Overview of completed clinical trials.
- Analysis of preclinical and translational data.
Main Results:
- Dose-intensification failed to improve high-risk disease outcomes.
- Preclinical research reveals novel targeted strategies.
- Early-phase trials show limited responses.
Conclusions:
- Targeted therapies offer new avenues for Ewing sarcoma.
- Lack of early response necessitates novel combination strategies.
- Future research should focus on innovative therapeutic approaches.
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