Research Knowledgebase

Dorraya El-Ashry, Ph.D. Associate Professor of Internal Medicine View full faculty profile

Description of Research

Breast cancer presents as either estrogen receptor α-positive (ERα+) or –negative
(ERα-), and the presence of ERα correlates with a better prognosis and response to hormonal therapy while the absence of ERα correlates with more aggressive and metastatic phenotypes, no response to hormonal therapies, and overexpression of growth factor receptors (GFRs) such as EGFR or c-erbB-2. Dr. El-Ashry's laboratory focuses on understanding the interaction between ERα signaling and GFR signaling in breast cancer progression. Using cell line models developed by her lab, scientists discovered that the overexpression of c-erbB-2 or EGFR directly induces the ERα- phenotype via the resultant hyperactivation of MAPK. Importantly, this MAPK induced down-regulation of ERα is reversible via abrogation of MAPK activity. Using genomic approaches, scientists were able to ascribe a major role for upregulation of MAPK activity in the biology of ERα- breast cancer and have identified specific MAPK substrates that are important for this biology. In addition, the lab also is establishing key EGFR and c-erbB-2 signaling substrates specifically in breast cancer cells as this is important for investigating interactions between ERα and GFR signaling pathways that may be responsible for initiating the generation of tumor cells that are either ERα+ or ERα-. The lab's cell line models are ideal to determine why high expression of ERα and EGFR/c-erbB-2 are mutually exclusive in breast cancer and thus the mechanisms that underlie the generation of the ERα+ versus ERα- phenotype. Most exciting is the very recent finding that inhibition of MAPK in primary cultures and explants from ERα- breast tumors can result in re-expression of ERα in a significant subset of specimens. Importantly, scientists have recently demonstrated that the re-expression of ERα in ERα- breast cancer cell lines and tumor cells via inhibition of MAPK activity was able to restore anti-estrogen sensitivity. These findings have tremendous implications for future therapeutics. Translating these laboratory studies to patient practice has the potential of being one of the most significant advances in breast cancer treatment for ERα- breast cancer.

Selected Cancer-Related Publications

Brinkman JA, El-Ashry D. ER re-expression and re-sensitization to endocrine therapies in ER-negative breast cancers. J Mammary Gland Biol Neoplasia 14:67-78, 2009. PubMed link

Bayliss J, Hilger A, Vishnu P, Diehl K, and El-Ashry D. Reversal of the Estrogen-Negative Phenotype and Restoration of Anti-Estrogen Response in Breast Cancer. Clinical Cancer Research, 13: 7029-7036, 2007. PubMed link

For full description of Multidisciplinary Research Program(s), Breast Cancer Program.