University of Colorado
Discovering ways to improve treatment response in patients with estrogen receptor-positive breast cancerDiscovering ways to improve treatment response in patients with estrogen receptor-positive breast cancer.
Breast cancers that are driven by estrogen—called estrogen receptor (ER)-positive, have the best five-year prognosis of any breast cancer. Despite effective therapies to treat ER-positive breast cancer, one-quarter to one-third of patients will experience a breast cancer recurrence. The goal of Drs. Horwitz and Sartorius’ BCRF research is to identify and test vulnerabilities in a common but understudied group of cells in ER-positive tumors that are ER-negative. This population of cells may be responsible for drug resistance and recurrence and behaves like cancer stem cells, which can initiate and drive cancer progression. By understanding how these cells promote tumor growth and identifying their weaknesses, she hopes to identify strategies to turn them off and prevent recurrence.
In the last year, Drs. Horwitz and Sartorius finished developing endocrine and drug-resistant variants of ER-positive breast cancer from her new breast cancer model system. Her team has identified prospective mechanisms for expansion of ER-negative “stem cell” populations that may drive tumor progression and have found that these cells often increase in number during the course of hormonal therapies and can interact with other cells that enable their travel through the bloodstream to form sites of metastasis. The team have also pinpointed changes in tumor DNA that confer therapeutic resistance in ER-positive breast cancer.
The team will use their ER-positive breast cancer model system to analyze the features and metastatic potential of circulating tumor cells and how long-term hormonal therapy affects them. In addition, Drs. Horwitz and Sartorius are analyzing changes in tumor cell DNA caused by a combination of long-term treatment with endocrine therapies and being in the bone environment, a common site of breast cancer metastasis. Understanding how hormone and drug environments impact ER-positive and metastatic breast cancer cells is imperative to stop disease progression.
Kathryn B. Horwitz, PhD joined the faculty at the University of Colorado after undergraduate studies at Barnard College, graduate studies at the UT Southwestern Medical School and postdoctoral work at UT San Antonio.
Research in her laboratory is both basic and translational. It focuses on the role of women’s hormones – estradiol and progesterone – and their receptors, on luminal breast cancer cell heterogeneity, growth, treatment, metastasis and stem cells. Her lab has extensive expertise in molecular and tumor-cell biology, using in vitro and in vivo models and clinical samples. Long-term goals are to improve the strategies and outcomes of therapies for luminal disease. Research topics include: transcriptional mechanisms of progesterone receptors; epigenetic and post-transcriptional receptor modifications and signaling cross-talk; hormones in cancer growth; mechanisms of resistance to endocrine therapies; hormones and regulation of breast cancer stem cells; intratumoral cell heterogeneity in luminal disease; hormonal regulation of metastasis and the stromal microenvironment; development of new breast cancer models, and translation of laboratory findings into clinical practice.
She has mentored numerous trainees who hold senior faculty posts at many US medical centers. She is a well-known national and international scholar, has served on multiple society boards, study sections and editorial boards, was elected President of the Endocrine Society, received its Fred Conrad Koch Award for exceptional contributions to endocrinology, and recently received the National Cancer Institute’s Rosalind E. Franklin Award for commitment to cancer research.
University of Colorado Anschutz Medical Campus
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