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Kathryn B. Horwitz, PhD
University of Colorado Denver
Goal: To discover ways to improve treatment response in patients with estrogen receptor (ER)-positive breast cancer.
Impact: Drs. Horwitz and Sartorius focus on a rare population of cells found in ER-positive breast tumors, called luminal breast cancer stem cells, that may play a role in some recurrences of cancer. Targeting these cells could improve patients’ response to endocrine therapy and prevent recurrence.
What’s next: The team will continue to conduct laboratory tests of luminal breast cancer cells that exploit the cells’ weaknesses as a means of targeted therapy.
While there are several effective therapies available for estrogen receptor (ER)-positive breast cancer, one-quarter of patients will experience a recurrence of their disease. New drugs are now used in combination with endocrine therapy (such as tamoxifen or aromatase inhibitors) to treat patients with recurrent breast cancer. These prolong survival, but do not save lives. Drs. Sartorius and Horwitz are studying ER-negative cells—which often co-exist with the ER-positive cells—and may be the cells driving recurrence in ER-positive breast cancer.
Full Research Summary
Research area: Identifying the underlying causes of drug resistance and breast cancer recurrence and strategies to improve outcomes.
Impact: Breast cancers that are driven by estrogen—called estrogen receptor (ER)-positive breast cancers, have the best five-year prognosis of any breast cancer. In spite of 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’s and Sartorius’ BCRF research is to identify and test vulnerabilities in a common but understudied group of cells in ER-positive tumors that may be responsible for drug resistance and recurrence. By understanding how these cells drive tumor growth and identifying their weaknesses, they hope to identify strategies to turn them off and prevent recurrence.
Current research: Drs. Horwitz and Sartorius are studying the role of ER-negative breast cancer stem cells in drug resistance and recurrence of ER-positive breast cancers.
What they’ve learned so far: The research team identified a small group of ER-negative cells that co-exist with ER-positive cells in breast cancer. These cells are resistant to anti-hormone (endocrine) therapies and have stem cell-like qualities that make them resistant to other drugs used in combination with endocrine therapies in patients with advanced breast cancer. They have discovered that these ER-negative cells have unique proteins that regulate cell shape and movement, which might explain why they lead to disease progression, and could be potential therapeutic targets.
What’s next: They will build on recent findings to target vulnerabilities in these ER-negative cells with the goal of developing unconventional strategies to improve response to endocrine therapy by targeting these cancer stem cells.
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.