Journal
ANNALS OF ONCOLOGY
Volume 21, Issue 4, Pages 683-691Publisher
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdp347
Keywords
biomarker; clinical trials; mTOR inhibitor; PI3K inhibitor; PI3K pathway; PTEN
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Funding
- European Society of Medical Oncology
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The phosphatidylinositol 3-kinase (PI3K) signalling pathway is integral to diverse cellular functions, including cellular proliferation, differentiation and survival. The 'phosphate and tensin homologue deleted from chromosome 10' (PTEN) tumor suppressor gene plays a critical role as a negative regulator of this pathway. An array of genetic mutations and amplifications has been described affecting key components of this pathway, with implications not only for tumorigenesis but also for resistance to some classic cytotoxics and targeted agents. Emerging preclinical research has significantly advanced our understanding of the PI3K pathway and its complex machinations and interactions. This knowledge has enabled the evolution of rationally designed drugs targeting elements of this pathway. It is important that the development of suitable biomarkers continues in parallel to optimize use of these agents. A new generation of PI3K inhibitors is now entering early clinical trials, with much anticipation that they will add to the growing armamentarium of targeted cancer therapeutics.
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