Novel Research on Invasive Breast Cancers
There are currently three main NIH-funded projects in Dr. Steven Ethier’s laboratory in the Developmental Cancer Therapeutics Program. The first project focuses on the 8p11-p12 genomic region which is amplified in approximately 15% of breast cancers and is associated with aggressive forms of estrogen receptor positive disease. Their working hypothesis is that this genomic region harbors a number of important breast cancer oncogenes that are responsible for the aggressive nature of this subset of diseases and provides novel therapeutic targets for patients who fail conventional endocrine therapy.
The second project is focused on triple negative breast cancers that over express the epidermal growth factor receptor (EGFR). One goal of this research is to determine the mechanisms by which altered EGFR activation by amphiregulin in SUM149 cells alters the biology of these cells and contributes to the aggressive phenotype observed in basal-type and triple-negative breast cancers.
The third main project in the laboratory focuses on the use of genome-wide shRNA libraries to identify genetic vulnerabilities in cancer cells, and to identify novel oncogenes in breast cancer. They are currently screening a panel of breast cancer cell lines developed in our lab using an shRNA library that targets ~16,000 human genes with a minimum of 5shRNAs per gene. Data from these screens are being combined with other genome-scale data sets to identify novel oncogenes and to unconver synthetic lethal interactions in cancer. The identified synthetic lethal interactions will be used to guide combination therapies that will enhance the effectiveness of and prevent the development of resistance to targeted therapies that are currently in use.