Towards Targeting PI3K-Dependent Regulation of Gene Expression in Brain Cancer.

The PI3K pathway is one of the most highly perturbed cell signaling pathways in human cancer, including the most common malignant brain tumors, gliomas, where either activating mutations of positive pathway effectors or loss/inactivation of pathway inhibitors occurs. Knowledge of the precise transcription factors modulated by PI3K in tumor cells remains elusive but there are numerous PI3K-responsive signaling factors, including kinases, which can activate many transcription factors. In the context of cancer, these transcription factors participate in the regulation of target genes expression networks to support cancer cell characteristics such as survival, proliferation, migration and differentiation. This review focuses on the role of PI3K signaling-regulated transcription in brain cancer cells from a series of recent investigations. A deeper understanding of this regulation is beginning to provide the hope of developing more sophisticated anti-cancer targeting approaches, where both upstream and downstream components of the PI3K pathway may be targeted by existing and novel drugs.