Pediatric Glioma: Role of Platelet-Derived Growth Factor Receptor

Abstract

Abundant evidence exists, especially in adult patients, implicating a critical role for PDGFR in the pathogenesis of human gliomas, including induction of primary oncogenesis as well as the maintenance of established glioma survival, growth, invasive spread, angiogenesis, and progression from lower to higher grades. More recent evidence also points towards a central role for PDGFR in maintaining neural stem cells in adults and in the possible recruitment of cancer stem cells and other CNS progenitor and facilitating cells leading to the development and progression of gliomas. Although the data are more limited in comparison to that described in the adult literature, emerging evidence now indicates that PDGFR amplification is the single most common genetic alteration in pediatric high-grade gliomas, including diffuse intrinsic pontine gliomas. However, the expression patterns and potential functional roles of PDGFR in gliomas may be distinct between adults and children. Investigations to establish the functional role and clinical relevance of PDGFR expression and PDGFR activity in childhood glioma are ongoing. Despite the lack of success to date of targeted PDGFR inhibitors in clinical trials for the treatment of high-grade gliomas, PDGFR remains an attractive target for the development of novel therapeutic strategies for gliomas given the critical role that PDGFR signaling plays in oncogenic growth- and survival-promoting pathways.