Breast cancer is a heterogeneous disease that can be subdivided into at least six subtypes. These subtypes are defined by their unique gene expression profiles, or transcriptomes. The transcriptomes specific to each subtype of breast cancer are well-characterized, but how these gene expression profiles are controlled remains to be determined. A few transcription factors have been linked to the expression of gene signatures in certain subtypes. However, the master regulatory mechanisms that control these differing phenotypes of breast cancer subtypes are not known.
In both normal cells and cancer cells, cellular phenotypes are not dictated by DNA sequence alone. Epigenetic modifications play a critical role in the regulation of gene expression which in turn dictates how cells behave. Epigenetics refers to various reversible changes to DNA that alter gene expression without changing the DNA sequence. Epigenetic gene regulation plays a critical role in development as well as in disease. In cancer, many epigenetic regulators have been found to be mutated and to drive various cancer types.
Epigenetic modification proteins are currently being studied as potential drug targets. Many drugs have been developed against epigenetic “writers” (proteins that add epigenetic marks), “erasers” (proteins that remove epigenetic marks), and “readers” (proteins that allow the cell to interpret epigenetic marks) and have entered into clinical trials. Our lab is currently investigating a number of drugs targeting the epigenome—in particular, those that inhibit eraser and reader proteins—to determine their efficacy in the most aggressive subtypes of breast cancer. We are also studying a number of epigenetic regulators to elucidate their function in mammary gland development and breast cancer. We hope these studies will lead to a greater understanding of the maintenance of breast cancer transcriptomes and the identification of novel therapeutic targets for the treatment of breast cancer.