Figure 1

The PI3K/Akt/mTOR signaling cascade. Simplified schemata of the PI3K/Akt/mTOR signaling cascade. While indisputable involved at several levels, directly as well as indirectly with cell survival, other important functions of this signaling network are also highlighted here. Key molecules which have been implicated in cancer or have been selected as potential therapeutic targets are: 1. Receptor tyrosine kinases, such as EGFR, IGFR and ALK, often overexpressed or activated by mutations in many different cancers, including glioblastoma and neuroblastoma. These transmembrane proteins are apical of several interconnected signaling cascades. 2. PI3K, phosphatidylinositol 3'-OH kinase, a lipid kinase, predominately consisting of a p110 catalytic and a p85 regulatory subunit, of which the former has been found to be mutationally activated in certain cancers. 3. PTEN, phosphatidylinositol (3,4,5)-triphosphate [PtdIns(3,4,5)P ₃ ] phosphatase and tensin homologue, is a phosphatase that counters PI3K-mediated phosphorylation and as such functions as a negative regulator of the PI3K/Akt/mTOR signaling cascade. It is among the most frequently inactivated, either by mutation or promoter methylation, proteins in cancer. 4. The serine/threonine kinase Akt, v-akt murine thymoma viral oncogene homologue (Protein Kinase B), is often considered the central downstream mediator of PI3K signaling, as it phosphorylates a diverse array of targets that are involved in all key functions of this pathway. 5. mTOR, mammalian target of Rapamycin, depending on its complex partners, can either be up- or downstream of Akt. It is frequently found to be associated with the process of autophagy, which depending on the context, can be either a survival strategy or a form of cell death. (modified from [33]).