The Development of Novel Small Molecule Inhibitors of the Phosphoinositide- 3-Kinase Pathway through High-Throughput Cell-Based Screens
Final rept. 12 Jan 2004-11 Jan 2007
DANA-FARBER CANCER INST BOSTON MA
Pagination or Media Count:
The PTENMMACTEP-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.
- Medicine and Medical Research