Predicting and Understanding Patient Responses to TopoII Isomerase Inhibitors in Breast Cancer
Abstract
Each year in the United States over 30,000 patients with breast cancer are treated with drugs whose mechanism of action is inhibition of TOP2 isomerase (TOP2). This protein uses energy to untangle DNA when cells try to divide. TOP2 solves an immense problem for the cell, which has over 2 yards of DNA packed into a space about 1/100 the size of a needle head. The DNA in this tiny space must be sorted and untangled within about 30 minutes in preparation for cell division. As one might expect, the class of drugs (anthracyclines) that block this vital process are plagued with complications that can be lethal, yet can also be highly effective treatments for breast cancer. Recently, we have found that we can predict whether cancer cells will respond to TOP2 inhibitors, and a major goal of this proposal will be to determine if we can save patients from the toxic effects of TOP2 inhibition with a simple genomic test. We also will determine the molecular mechanism underlying resistance to TOP2 inhibitors in breast cancer. Our long-range goals are to save patients from treatment with this highly toxic class of drugs if there is no chance that they will benefit from their use. By performing a simple genomic test on the patient s tumor sample obtained for pathologic diagnosis, we hope to be able to personalize breast cancer treatment, avoiding toxic drugs and allowing the use of other effective treatments. We anticipate that we will be able to conduct a thorough test of this idea in about 2 to 3 years for breast cancer in the United States.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1610083
Entities
People
- Gerald Crabtree
Organizations
- Stanford University
- United States Army