In vitro and in vivo modeling systems of supratentorial ependymomas

Emily A Hatanaka; Joshua J Breunig

doi:10.3389/fonc.2024.1360358

In vitro and in vivo modeling systems of supratentorial ependymomas

Front Oncol. 2024 Feb 26:14:1360358. doi: 10.3389/fonc.2024.1360358. eCollection 2024.

Authors

Emily A Hatanaka^{1

2}, Joshua J Breunig^{1

2

3

4

5}

Affiliations

¹ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
² Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
³ Center for Neural Sciences in Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
⁴ Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
⁵ Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Abstract

Ependymomas are rare brain tumors that can occur in both children and adults. Subdivided by the tumors' initial location, ependymomas develop in the central nervous system in the supratentorial or infratentorial/posterior fossa region, or the spinal cord. Supratentorial ependymomas (ST-EPNs) are predominantly characterized by common driver gene fusions such as ZFTA and YAP1 fusions. Some variants of ST-EPNs carry a high overall survival rate. In poorly responding ST-EPN variants, high levels of inter- and intratumoral heterogeneity, limited therapeutic strategies, and tumor recurrence are among the reasons for poor patient outcomes with other ST-EPN subtypes. Thus, modeling these molecular profiles is key in further studying tumorigenesis. Due to the scarcity of patient samples, the development of preclinical in vitro and in vivo models that recapitulate patient tumors is imperative when testing therapeutic approaches for this rare cancer. In this review, we will survey ST-EPN modeling systems, addressing the strengths and limitations, application for therapeutic targeting, and current literature findings.

Keywords: CNS tumor; brain cancer; glioma; oncofusion proteins; pediatric tumor; rare cancer; tumor modeling.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. We acknowledge support from the Board of Governors RMI of Cedars-Sinai (to JB). JB was supported by DoD grant HT9425-23-1-0269, NIH grant R33CA236687, American Cancer Society grant RSG-16-217-01-TBG. EH was supported by the CIRM Fellowship EDUC4-12751.