Atypical PKCι as target for glioblastoma therapy.

ABSTRACT

Glioblastoma (grade IV astrocytoma) is an aggressive and incurable form of brain tumor. It invariably shows extensive invasion at the time of diagnosis, often involving both hemispheres. Recent studies have given us a very detailed picture of glioblastoma genetics. These paint a picture of a disease with extensive heterogeneity, both between patients and within individual patients. This within patient heterogeneity presents a major challenge in the design of targeted therapies. One approach is to identify targets that are common downstream elements in signaling pathways that are aberrantly activated in glioblastoma. Here we review the evidence that the atypical protein kinase C family member PKCι may fulfill this role. Our current understanding of PKCι activation mechanisms is discussed and related to common genetic changes in glioblastoma. The data showing an essential role for PKCι in multiple aspects of glioblastoma pathology are also reviewed. Finally, data on the role of PKCι in normal brain function are reviewed for insights into potential side effects of PKCι inhibition in the central nervous system.