Several features make the PI3K/Akt/mTOR pathway one of the most significant in human cancers:
- Mutations in PI3Ka and/or PTEN occur in a majority of human tumors.
- Dysregulation or over-expression of PI3K and Akt occur frequently.
- PI3Kβ mediates PTEN-deficient tumorigenesis, as well as, tumor-associated GPCR signaling, such as S1P and LPA
- Recent studies have delineated specialized functions in tumorigenesis for PI3Kα and PI3Kβ
- Activation of the PI3K/Akt/mTOR pathway contributes to cell growth, cell cycle entry, cell survival, angiogenesis, ribogenesis, metabolism and cell motility - all critical aspects of tumorigenesis.
- Persistent signaling through the PI3K/Akt/mTOR pathway shown to be a major mechanism of resistance.
Several features make the PI3K/Akt/mTOR pathway one of the most druggable pathways in cancer:
- The preclinical science and experimental medicine of PI3K/Akt/mTOR inhibitors is evolving rapidly.
- The first-generation, selective inhibitors have taught some valuable lessons for the design of best-in-class candidates.
- The PI3K/mTOR/Akt pathway is highly amenable to biomarker-driven clinical trial design.
- There is a significant opportunity to use inhibitors of the PI3K/Akt/mTOR pathway in combination therapy regimens.
These data underscore the widespread potential utility of inhibitors of the PI3K/Akt/mTOR pathway as agents for the treatment of human cancers.
Intellikine has developed selective TORC1/2 kinase inhibitors and PI3Kα/β inhibitors to treat cancers driven by the PI3K/Akt/mTOR pathway.