A number of agents have begun testing for this project. One agent, a MEK inhibitor, has been evaluated as a radiation sensitizer both in vitro and in vivo. The agent was found to sensitize three histologies to radiation in vitro and to sensitize two tested cell lines to radiation in subcutaneous xenografts. Additional mechanistic work has revealed that the cause of this senstization appears to be related to abrogation of the G2 checkpoint after irradiation. Additional work with this compound is focusing on possible biomarkers of effect to identify candidate markers of efficacy for clinical translation. In addition, we are currently testing the agent in combination with other targeted agents or with chemotherapy. A clinical trial has recent;y been initiated with this compound with myself as the Pricipal Investigator. Two additional agents are currently undergoing testing for efficacy as radiation sensitizers. These include a small molecule poly(ADP-ribose) polymerase (PARP) inhibitor and a multi-target tyrosine kinase inhibitor. The preliminary in vitro clonogenic assays have been promising for these two compounds. Additional in vitro work, in vivo work, and mechanistic work will be ongoing. The eventual goal for these compounds is clinical translation into trials as radiation sensitizers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010849-04
Application #
8157502
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2010
Total Cost
$612,188
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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