Accession Number:

ADA478482

Title:

Fatty Acid Synthase Inhibitors Engage the Cell Death Program Through the Endoplasmic Reticulum

Descriptive Note:

Annual rept. 1 Dec 2006-30 Nov 2007

Corporate Author:

WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF HEALTH SCIENCES

Personal Author(s):

Report Date:

2007-12-01

Pagination or Media Count:

106.0

Abstract:

Fatty acid synthase FAS, the enzyme that synthesizes the 16-carbon fatty acid palmitate, in highly expressed in prostate cancer. Because of a corresponding lack of expression in normal prostate, FAS is an attractive drug target. We have described the endoplasmic reticulum ER stress response as a critical mediator of the anti-tumor effects of FAS inhibitors. In this report we also describe a novel connection between the FAS pathway and the proteasome pathway. This feedback between the two pathways can further be antagonized by co-treatment with the FDA-approved proteasome inhibitor Velcade. Velcade synergizes with FAS inhibitors to induce cell death and increase ER stress related signaling. These aspects will be followed up in vitro and in vivo. The importance of these studies is underscored by the potential relevance of FAS as a drug target in prostate cancer. Several FAS inhibitors have been developed, but none have been translated into the clinic thus far. These studies will be valuable as FAS inhibitors move toward a clinical setting.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE