Targeted Oncology

, Volume 6, Issue 2, pp 103–117

Targeting phosphatidylinositol 3 kinase (PI3K)-Akt beyond rapalogs

Review

DOI: 10.1007/s11523-011-0176-7

Cite this article as:
Ogita, S. & LoRusso, P. Targ Oncol (2011) 6: 103. doi:10.1007/s11523-011-0176-7
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Abstract

The activation of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway is a known causal mechanism of oncogenesis and resistance to cancer treatments. The process of PI3K-Akt pathway activation is complex and includes receptor tyrosine kinase(RTK) activation, PIK3CA mutations, loss of phosphatase and tensin homolog (PTEN), Akt mutations, tuberous sclerosis complex (TSC) mutations, and Ras homologue enriched in brain (RHEB) gene amplifications. The blockage of mammalian target of rapamycin (mTOR), the key downstream pathway protein, has been successful in selected cancer types, with mTOR-targeting agents available for clinical use. Other novel drugs blocking this pathway such as PI3K inhibitors, Akt inhibitors and PDK-1 inhibitors are currently only available for investigational use, but have shown promise as cancer therapies in both preclinical and early phase clinical studies. The newer generations of these inhibitors are more specific and have improved potency and safety. The combinations of targeted treatments against this pathway, blocking multiple different steps, are under preliminary investigation. Further research is needed to identify the biomarkers that predict treatment response and resistance in order to optimize personalized medicine.

Keywords

PI3K Akt PDK-1 Inhibitor PTEN mTOR 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Karmanos Cancer InstituteWayne State UniversityDetroitUSA

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