Effect of VEGFR, PDGFR and PI3K/mTOR Targeting in Glioblastoma.

ABSTRACT

Resistance to targeted therapy is a well known obstacle in cancer therapy. The cross-talk between several growth factor receptors generates redundancy in their intracellular pathways that usually mediates resistance to receptor targeted therapy. Simultaneous inactivation of two or more growth factor receptors has been suggested to prevent the cross-talk between their signaling pathways and to better eliminate malignant cells. Here we found that targeted therapy against these receptors induced moderate cell death in glioblastoma cells. More important, dual PDGFR and VEGFR inactivation induced more pronounceable cell death compared to inactivation of each receptor alone but failed to induce synergistic cell death in glioblastoma. PI3K/mTOR dual targeting has been identified as an efficient therapeutic approach in several malignant diseases, including glioblastoma. Therefore, we also investigated the PI3K/mTOR pathways inhibition effect in glioblastoma cells. Our results showed that inactivation of PI3K/mTOR pathways were more efficient than PDGFR or VEGFR single targeting or their dual inhibition.