Monique Spillman, MD, PhD
University of Colorado, Denver
Modulation of Estrogen Response in a Mouse Xenograft Model of Steroid Hormone Sensitive Ovarian Cancer
Project Summary
Women are exposed to estrogen, the female steroid hormone, throughout their reproductive lives. As natural levels of estrogen fall in menopause, some women have taken hormone replacement therapy containing estrogen. When estrogen alone is taken in the menopause, it appears to increase the risk of developing ovarian cancer.
Estrogen acts through the estrogen receptor (ER). At least 60% of ovarian cancers express the estrogen receptor, but it appears to act differently in ovarian cancers than in breast cancers. My research project is designed to identify estrogen regulated genes in ovarian cancers that may differ from those in breast cancers. We are also investigating drugs that inhibit estrogen receptor action in breast cancer, such as tamoxifen and letrozole in ovarian cancers.
Extended use of estrogen is difficult to mimic in short term cell culture models. For this reason, I have developed a unique ovarian cancer mouse model which allows rigorous, long-term, control of the steroid hormone (estrogen) microenvironment. When ER+ ovarian cancer cells are introduced into the model, they grow significantly. ER- cells in the same model demonstrate some growth, but lag behind the ER+ cells.
Women with advanced ovarian cancer are initially treated with a combination of surgery, followed by chemotherapy. Several maintenance chemotherapies have been tried to decrease the risk of recurrence; however, antiestrogen or aromatase inhibitor therapy has not been tried in this setting as a secondary preventative agent. We will use the mouse model to test the antiestrogen tamoxifen and aromatase inhibitor letrozole for effectiveness in inhibiting growth of ovarian tumors. In addition, we will examine ovarian tumors treated with estrogen, tamoxifen and letrozole to identify different patterns of gene expression.
Development of the mouse model has placed my research in a unique position to define the role of estrogen in the development and recurrence of ovarian cancer. The goal of this project is to identify new drug targets from the sets of estrogen regulated genes identified in our model system. In addition, our research may define a subset of women with ovarian cancer who may benefit from the addition of a hormonal agent to the standard chemotherapy.
Bio
Dr. Spillman was born in Victorville, California, the daughter of Lt. Col. (Ret.) James A. Spillman and Alice G. Spillman. She graduated from Santa Anna High School in Santa Anna, Texas, as the valedictorian. She enrolled in the University of Texas at Austin in the Dean’s Scholars Honors Program of the College of Natural Sciences. After graduating with a Bachelor of Arts in Biochemistry with High Honors, she enrolled in the University of Texas Southwestern Medical School in Dallas, Texas.
At UT Southwestern, Dr. Spillman participated in the combined Medical Scientist Training Program which culminated in the awarding of both the MD and PhD degrees. Her PhD thesis was entitled, “Estrogen Regulated Genes in Breast and Ovarian Cancer.”
She pursued clinical training in Obstetrics and Gynecology at the Brigham and Women’s/Massachusetts General Hospital Integrated Residency Program in Boston, Massachusetts. She completed a fellowship in gynecologic oncology at Duke University Medical Center in Durham, North Carolina.
Dr. Spillman has been an Assistant Professor of Obstetrics and Gynecology at the University of Colorado Denver since 2003. She also serves as a Women’s Reproductive Health Research Fellow at UCD. She continues to pursue her interest in hormone regulated genes within the Program of Excellence in Cancers of the Ovary in Colorado (PECOC).
Press
"Spillman's Liz Tilberis Scholars Award." University of Colorado Cancer Center Director's Message, April 7, 2009.
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