The Development of Novel Small Molecule Inhibitors of the Phosphoinositide- 3-Kinase Pathway through High-Throughput Cell-Based Screens
Abstract
The PTEN/MMAC/TEP-1 tumor suppressor gene (hereafter referred to as PTEN) is a target of somatic mutation in prostate cancer as well as in endometrial cancer, glioblastoma and melanoma (reviewed in (Sansal and Sellers, 2004)) Biallelic loss of PTEN has been demonstrated in both primary and metastatic prostate tumors (reviewed in (Sansal and Sellers, 2004)). In metastatic disease, PTEN loss approaches 50%-60% (Suzuki et al., 1998). Together, these data suggest that loss of PTEN is an important step for those prostate tumors associated with a lethal outcome. Moreover, the loss of PTEN has been intimately linked to deregulation of the PI3K pathway connecting growth and survival signals both to the regulation of the mTOR kinase as well as to the regulation of the FOXO transcription factors. A significant effort is now being expended in the pharmaceutical industry in trying to develop regulators of the PI3K pathway (or more specifically inhibitors) that can reverse the molecular consequences of PTEN loss.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2007
- Accession Number
- ADA467904
Entities
People
- Wiliam R. Sellers
Organizations
- Dana–Farber Cancer Institute