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The PTEN/PI3 Kinase Pathway in Human Glioma

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CNS Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Phosphoinositide 3-kinase (PI3K) was discovered over 20 years ago as an enzyme that was active in growth factor-stimulated and oncogene-transformed cells. Ten years later, the PTEN gene was isolated by its deletion in a large proportion of human cancers, including glioblastoma. These two areas of research converged when it was shown that PTEN dephosphorylated the lipid product of PI3K activity, phosphatidylinositol (3,4,5) trisphosphate, or PIP3. Furthermore, it has since become clear that PTEN has tumor-suppressive activities that are independent of its lipid phosphatase activity. This chapter reviews the importance of PI3K activity in the development of glioblastoma, by describing the different genetic and epigenetic alterations that occur to deregulate the activity of this pathway. It will also describe the regulation of PTEN expression and activity, by transcriptional and posttranslational processes. Recent results implicating PI3K activity and PTEN in the cells that are thought to initiate early brain tumor development (brain tumor stem cells) are also reviewed. Finally, the possibilities of using this pathway both as a direct therapeutic target and as a way of predicting response to recently developed drugs are discussed.

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Authors and Affiliations

  1. Ludwig Institute for Cancer Research, University of California-San Diego School of Medicine, 9500 Gilman Drive CMM-East Rm. 3020, 92093-0660, La Jolla, CA, USA

    David Stokoe & Frank B. Furnari

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  1. David Stokoe
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  2. Frank B. Furnari
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Correspondence to Frank B. Furnari .

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  1. School of Medicine, Emory University, Clifton Road 1365C, Atlanta, 30322, U.S.A.

    Erwin G. Meir

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Stokoe, D., Furnari, F.B. (2009). The PTEN/PI3 Kinase Pathway in Human Glioma. In: Meir, E. (eds) CNS Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60327-553-8_15

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