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Annals of Oncology Advance Access published online on August 27, 2009
Annals of Oncology, doi:10.1093/annonc/mdp347
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

review

Status of PI3K inhibition and biomarker development in cancer therapeutics

B. Markman, F. Atzori, J. Pérez-García, J. Tabernero and J. Baselga*

Medical Oncology Service, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain

* Correspondence to: Dr J. Baselga, Medical Oncology Service, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain. Tel: +34 93 274 6077; Fax: +34 93 274 6059; E-mail: jbaselga{at}vhebron.net

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.

biomarker, clinical trials, mTOR inhibitor, PI3K inhibitor, PI3K pathway, PTEN

Received for publication April 17, 2009. Revision received May 28, 2009. Accepted for publication May 29, 2009.


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