It has been shown that the dysregulated receptor tyrosine kinase (RTK, including EGFR, MET, PDGFRα, ect.) signaling pathways have pivotal roles in the progression of gliomas, especially glioblastoma.
We also detected amplifications of epidermal growth factor receptor (EGFR) or platelet-derived growth factor receptor alpha (PDGFRalpha) in a few of the 13 cases of glioblastoma multiforme analyzed.
These results indicate that GBM growth responses to targeted therapies previously tested in clinical trials are strongly influenced by the balance of EGFR and PDGFRA activation in individual cells, which is heterogeneous at baseline.
In summary, our results show that well-tailored RNA aptamers targeting the PDGFRα-STAT3 axis have the potential to act as anti-cancer therapeutics in GBM.
We found that PDGFRα is expressed only in a subset of GBMs, while PDGFRβ is more commonly expressed in tumors but is preferentially expressed by self-renewing tumorigenic GBM stem cells (GSCs).
Phosphorylated receptor tyrosine kinase profiling showed a specific activation of platelet-derived growth factor receptor alpha/beta in EGFRvIII-transduced pediatric glioblastoma cells, and targeted coinhibition with erlotinib and imatinib leads to enhanced efficacy in this model.
The association of PDGFR-alpha expression with a distinct subset of glioblastomas characterized by loss of heterozygosity 17p further supports the differentiation of these tumors into molecular variants.