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Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Therapeutic Targeting of Cancers with Loss of PTEN Function

Author(s): Lloye M. Dillon and Todd W. Miller

Volume 15, Issue 1, 2014

Page: [65 - 79] Pages: 15

DOI: 10.2174/1389450114666140106100909

Price: $65

Abstract

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is one of the most frequently disrupted tumor suppressors in cancer. The lipid phosphatase activity of PTEN antagonizes the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway to repress tumor cell growth and survival. In the nucleus, PTEN promotes chromosome stability and DNA repair. Consequently, loss of PTEN function increases genomic instability. PTEN deficiency is caused by inherited germline mutations, somatic mutations, epigenetic and transcriptional silencing, post-translational modifications, and protein-protein interactions. Given the high frequency of PTEN deficiency across cancer subtypes, therapeutic approaches that exploit PTEN loss-of-function could provide effective treatment strategies. Herein, we discuss therapeutic strategies aimed at cancers with loss of PTEN function, and the challenges involved in treating patients afflicted with such cancers. We review preclinical and clinical findings, and highlight novel strategies under development to target PTENdeficient cancers.

Keywords: Cancer, phosphatase, targeted therapy, tumor, tumor suppressor, PI3K, mTOR, synthetic lethal.


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