Studies of a Ras Antagonist in Breast Cancer
Abstract
Deprivation of estrogen, called Endocrine Therapy (ET), is commonly used to treat women with estrogen receptor (ER) positive breast cancer. Resistance to ET occurs in a many women after about 18 months of treatment. Upregulation of growth factor pathways mediated by the 21 kDa Ras GTPase protein may contribute to resistance to ET. A novel Ras antagonist, farnesylthiosalicylate (FTS), causes Ras downregulation with concomitant abrogation of growth factor pathways. We tested the ability of FTS, which was complexed to a cyclodextrin moiety for solubility, to reduce the growth of ER positive breast cancer cells that were resistant to ET. FTS prevented growth of ER positive breast cancer cells by increasing apoptosis and reducing proliferation. Accompanying loss of cell growth was a significant reduction in the response to estrogen. The loss of estrogen response may have been due to an observed loss of ER protein in response FTS treatment. FTS might be causing reduced cell growth in part by increasing turnover of the ER in ER positive breast cancer cells. FTS was additive with Doxorubicin in vitro. We suggest that the FTS should enter preclinical trials against ER positive breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA425819
Entities
People
- Richard J. Santen
Organizations
- University of Virginia