Related Experiment Video
Updated: Jun 16, 2026
A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma DIPG
Published on: March 7, 2017
Development of Chromosome 1q+ Specific Treatment for Highest Risk Pediatric Posterior Fossa Ependymoma
Andrea M Griesinger1,2, Annaliese J Calzadilla1,2, Enrique Grimaldo1,2
1Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children's Hospital Colorado, Aurora, Colorado.
Insights
New combination therapy shows promise for high-risk pediatric ependymoma (PFA). This approach combines 5-fluorouracil (5FU), ATRA, and radiation, targeting chromosome 1q gains (1q+) in PFA tumors, offering hope for improved survival.
Area of Science:
- Pediatric Oncology
- Cancer Genetics
- Radiation Oncology
Background:
- Highest-risk posterior fossa group A ependymoma (PFA) lacks effective treatments.
- Chromosome 1q gains (1q+) are common in PFA, especially at recurrence, and are associated with poor outcomes.
- Developing targeted therapies for 1q+ PFA is critical.
Purpose of the Study:
- To evaluate the preclinical efficacy of combined radiation and chemotherapy for 1q+ PFA.
- To investigate the role of chromosome 1q in treatment response.
Main Methods:
- Utilized in vitro and in vivo models of 1q+ PFA.
- Tested combination therapy including 5-fluorouracil (5FU), ATRA, and radiation.
- Assessed cellular proliferation and apoptosis markers.
Main Results:
- 5-fluorouracil (5FU) enhanced radiotherapy in 1q+ PFA cell lines by increasing p53 activity via UCK2 on chromosome 1q.
- Combined 5FU, ATRA, and radiation significantly reduced proliferation and increased apoptosis in vitro.
- In vivo studies showed enhanced survival in mice treated with the combination therapy.
Conclusions:
- This study identifies the first chromosome 1q+ specific therapy for 1q+ PFA.
- The established safety and dosage of 5FU and ATRA in pediatric Phase I trials support expedited clinical application in Phase II trials for high-risk PFA.
Purpose:
There are no effective treatment strategies for children with highest-risk posterior fossa group A ependymoma (PFA). Chromosome 1q gains (1q+) are present in approximately 25% of newly diagnosed PFA tumors, and this number doubles at recurrence. Seventy percent of children with chromosome 1q+ PFA will die because of the tumor, highlighting the urgent need to develop new therapeutic strategies for this population.
Experimental Design:
In this study, we utilize 1q+ PFA in vitro and in vivo models to test the efficacy of combination radiation and chemotherapy in a preclinical setting.
Results:
5-fluorouracil (5FU) enhances radiotherapy in 1q+ PFA cell lines. Specifically, 5FU increases p53 activity mediated by the extra copy of UCK2 located on chromosome 1q in 1q+ PFA. Experimental downregulation of UCK2 resulted in decreased 5FU sensitivity in 1q+ PFA cells. In in vitro studies, a combination of 5FU, retinoid tretinoin (ATRA), and radiation provided the greatest reduction in cellular proliferation and greatest increase in markers of apoptosis in 1q+ PFA cell lines compared with other treatment arms. Similarly, in vivo experiments demonstrated significant enhancement of survival in mice treated with combination radiation and 5FU and ATRA.
Conclusions:
These results are the first to identify a chromosome 1q+ specific therapy approach in 1q+ PFA. Existing phase I studies have already established single-agent pediatric safety and dosages of 5FU and ATRA, allowing for expedited clinical application as phase II trials for children with high-risk PFA.
More Related Videos
Related Concept Videos
02:56Treatment Resistant Cancers
02:56Treatment Resistent Cancers