The phosphoinositide 3-kinase signaling pathway as a therapeutic target in grade IV brain tumors

Höland, K; Salm, F; Arcaro, A (2011). The phosphoinositide 3-kinase signaling pathway as a therapeutic target in grade IV brain tumors. Current cancer drug targets, 11(8), pp. 894-918. Hilversum: Bentham Science Publishers

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Brain tumors comprise a wide variety of neoplasia classified according to their cellular origin and their morphological and histological characteristics. The transformed phenotype of brain tumor cells has been extensively studied in the past years, achieving a significant progress in our understanding of the molecular pathways leading to tumorigenesis. It has been reported that the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway is frequently altered in grade IV brain tumors resulting in uncontrolled cell growth, survival, proliferation, angiogenesis, and migration. This aberrant activation can be explained by oncogenic mutations in key components of the pathway or through abnormalities in its regulation. These alterations include overexpression and mutations of receptor tyrosine kinases (RTKs), mutations and deletions of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene, encoding a lipid kinase that directly antagonized PI3K activity, and alterations in Ras signaling. Due to promising results of preclinical studies investigating the PI3K/AKT pathway in grade IV brain tumors like glioblastoma and medulloblastoma, the components of this pathway have emerged as promising therapeutic targets to treat these malignant brain tumors. Although an arsenal of small molecule inhibitors that target specific components of this signaling pathway is being developed, its successful application in the clinics remains a challenge. In this article we will review the molecular basis of the PI3K/AKT signaling pathway in malignant brain tumors, mainly focusing on glioblastoma and medulloblastoma, and we will further discuss the current status and potential of molecular targeted therapies.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Höland, Katrin; Salm, Fabiana and Arcaro, Alexandre

ISSN:

1568-0096

Publisher:

Bentham Science Publishers

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:24

Last Modified:

06 Dec 2013 13:29

PubMed ID:

21861842

Web of Science ID:

000298244600001

URI:

https://boris.unibe.ch/id/eprint/8324 (FactScience: 213845)

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