Because their aberrant activity is implicated in human cancer, ErbB receptor tyrosine kinases (ErbB1/EGFR, ErbB2/HER2/neu, ErbBS, and ErbB4) have become targets of cancer therapeutics designed to interfere with their signaling by inhibiting ligand binding, receptor dimerization, and kinase activity. While the first generation of these drugs shows promise, we are just beginning to appreciate the details of how they work (e.g., alterations to receptor trafficking) and in which contexts (i.e., ErbB expression profiles) particular agents (or combinations thereof) may be most effective. To enhance this understanding, we propose an experimental and modeling approach. Using cell lines with known ErbB profiles, we will measure the ability of various inhibitors to interrupt ErbB-mediated signaling and the effects of those inhibitors on ErbB trafficking (internalization, recycling, degradation). Using measured parameters, we will develop an ErbB trafficking and signaling model to enable prediction of which therapeutics will be most effective for a given ErbB profile. Ultimately, this work portends enhanced understanding of how to better design ErbB-targeted agents and how to best treat individuals with available therapies based on their ErbB expression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA117721-01
Application #
6997989
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Lohrey, Nancy
Project Start
2005-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$48,296
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139