Accession Number:

ADA509136

Title:

Targeting Signal Transducers and Activators of Transcription-3 (STAT3) as a Novel Strategy in Sensitizing Breast Cancer to EGFR-Targeted Therapy

Descriptive Note:

Annual rept. 1 Jun 2008-31 May 2009

Corporate Author:

DUKE UNIV DURHAM NC

Personal Author(s):

Report Date:

2009-06-01

Pagination or Media Count:

10.0

Abstract:

Our research effort in the past award year has resulted in several interesting findings that support the study hypothesis deregulated EGFR and STAT3 pathways synergistically contribute to the malignant biology of breast cancer and that combined uses of anti-EGFR and anti- STAT3 treatments result in significantly increased breast cancer cell death compared to single agent treatments. First, we have created isogenic breast cancer cell lines to stably express modestly activated and highly activated STAT3, STATCA. Second, using these established isogenic breast cancer cell lines, we found that increased STAT3 activation rendered breast cancer cells resistant to EGFR targeted therapy. Third, we showed that STAT3 expression knock-down sensitized EGFR-expressing breast cancer cells to anti-EGFR therapy. Finally, our in vitro results showed that combined used of a STAT3 small molecular weight inhibitor AG490 and a clinically used EGFR inhibitor Iressa synergistically targeted EGFR-expressing breast cancer cells to anti-EGFR therapy.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE