Oncogenes and Tumor Suppressor Genes, Gene Regulation and Transcription Factors, Tumor progression, invasion and metastasis and Cellular and Tumor Microenvironment
Hormone related malignancies and microRNAs
University of Colorado Anschutz Medical Campus, Dept of Pathology, Aurora
To determine the molecular mechanisms whereby the female hormones estrogen and progesterone affect breast, unterine, and ovarian cancers.
Some current areas of focus include:
The role of androgen receptor (AR) in both estrogen receptor alpha (ERa) positive and negative breast cancer. We recently discovered that the ratio of AR to ER protein in breast cancers may play a role in response to traditional ER directed endocrine therapies such as tamoxifen and aromatase inhibitors. We find that a new generation anti-androgen that acts by excluding AR from the nucleus, has anti-tumor activity in vivo in both ER+ and ER- breast cancers that retain AR expression. Our efforts in the laboratory recently led to the initiation of a phase 1 clinical trial in breast cancer with the anti-androgen enzalutamide which has been demonstrated to be effective in castrate resistant prostate cancer.
The role of microRNAs in breast and gynecologic cancers. Previous studies in the lab have identified specific microRNAs that are different in ER+ versus negative breast cancers. ER+ breast cancers have much higher levels of Dicer, a protein involved in microRNA biogenesis and express more abundant and higher levels of miRNAs in general. We have identified specific miRNAs that influence the clinical behavior of women’s cancers by affecting hormone receptor status, loss of epithelial characteristics, gain of mesenchymal and neuronal traits, tumor metabolism and chemosensitivity. Our goal is to conduct further pre-clinical studies to evaluate the potential therapeutic value of specific microRNA based therapies for aggressive breast, endometrial and ovarian cancers in preclinical models.