2008 UALC
Esther Black, PhD
University of Kentucky
Research Project:
Dual targeted therapy: Can MEK inhibition improve response and reduce acquired resistance in EGFR-dependent NSCLC?
Summary:
While EGFR inhibitors can be very effective in initial treatment of patients harboring EGFR mutations, patients quickly develop resistance to these treatments. Dr. Black is investigating a drug targeting another pathway (MAPK) that may improve patient responses to EGRF-targeting drugs. This work will provide initial data for a future clinical trial testing a MAPK inhibitor in combination with an EGFR inhibitor.
More Content:
Final Report
Dr. Black has completed the in vivo analysis of combination treatment of the MEK inhibitor and Iressa in xenograft models. While initial in vitro studies showed synergism, Dr. Black was unable to replicate significant differences in treatment. Further analysis of the molecular mechanisms showed some unexpected results, demonstrating that there may be other compensatory mechanisms controlling down-regulation of the EGFR protein in vivo, in addition to MEK signaling. Dr. Black and her team are continuing to investigate how this pathway regulates EGFR, and how tumors become resistant to treatment.
Notable Accomplishments
Dr. Black was awarded $25,000 from the Peter Bradley Carlson Charitable Trust and a $25,000 Developmental Award from the NIH. Studies from Aim 1 have been published in Cancer Biology & Therapy, and Dr. Black has a second manuscript in preparation.