Pten-Deficient Mouse Models for High-Grade Astrocytomas

Despite vigorous efforts in clinics and laboratories, the overall prognosis for patients with glioblastoma multiforme (GBM), the most common and aggressive glioma, has not greatly improved over the last few decades. Innovative new therapies based on detailed molecular mechanisms of glioma biology are highly desired. Mutation or loss of PTEN (phosphatase tensin homolog deleted on chromosome ten), a key phosphatase that antagonizes the PI3K/AKT pathway, is one of the most frequent abnormalities found in high-grade astrocytomas. Whether this genetic alteration is causal or consequential to the tumorigenic process has begun to be elucidated through tumor genetics and new mouse models. This chapter describes the key findings from mouse astrocytoma models involving Pten deficiency or Akt activation, with specific emphasis on the recently reported Pten-heterozygous mouse models. In addition, future directions to inform the design of novel therapeutics for this devastating disease are discussed.