Benita S. Katzenellenbogen, PhD

The estrogen receptor (ER) is the master regulator of over 60% of breast cancers and is the major target for endocrine therapies (e.g., tamoxifen or aromatase inhibitors). While very effective, these therapies are often compromised by the development of resistance. Dr. Katzenellenbogen and her research group are identifying new ways in which resistance to endocrine therapies may be avoided or reversed. They have investigated the biological functions of genes that they have found to be specifically regulated by tamoxifen. They have examined the correlation of these genes with disease-free survival of breast cancer patients on endocrine therapy and find that they are predictive of patient benefit from endocrine therapies.

In addition, using novel probes they have developed, they have been exploring how estrogens act from the membrane as well as the nucleus of breast cancer cells to regulate gene expression and activate cell pathways that contribute to the development of endocrine resistance. This research has identified markers that could be used to tailor treatments based on characteristics of the breast cancers of individual patients and provides leads to ways in which resistance to endocrine therapies might be prevented or reversed.

Because the effectiveness of endocrine therapy in breast cancer (generally anti-estrogens such as tamoxifen or aromatase inhibitors) is often compromised by the development of endocrine resistance, Dr. Katzenellenbogen and her research group will expand their genomic studies using novel estrogen and anti-estrogen probes they have developed to analyze how estrogen receptor actions via the nucleus and also initiated from the membrane are integrated so as to regulate gene expression patterns associated with aggressiveness and outcome of patients on endocrine therapy.

These studies, analyzing the integration of signaling pathways that link estrogen genomic and non-genomic actions and growth factor actions in breast cancer, should highlight new ways in which endocrine resistance might be reduced or reversed by identifying signaling components that could be targeted for breast cancer prevention or treatment, either alone or in synergistic combination with established endocrine therapies.

Mid-Year Progress Report:
Dr. Katzenellenbogen and her research group are using novel estrogen and anti-estrogen probes they have developed to elucidate how resistance to endocrine therapies develops in breast cancer and how it can be avoided or reversed. In genomic studies in breast cancer cells, they have found that estrogen receptor actions initiated outside the cell nucleus account for 25% of the gene regulations by estrogen, and they have shown that inputs from estrogen receptor actions via the nucleus and also initiated from the membrane are integrated so as to regulate gene expression patterns associated with aggressiveness and outcome of patients on endocrine therapy.

These studies document important cross talk in signaling pathways that link estrogen nuclear and extranuclear actions with growth factor actions in breast cancer. The findings highlight new ways in which endocrine resistance might be reduced or reversed by identifying signaling components that could be targeted for breast cancer prevention or treatment, either alone or in synergistic combination with established endocrine therapies involving anti-estrogens such as tamoxifen or aromatase inhibitors.

Bio:
Benita Katzenellenbogen is Swanlund Professor of Physiology, Cell and Structural Biology, and director of a breast cancer research group at the University of Illinois and University of Illinois College of Medicine at Urbana-Champaign. She is an internationally known endocrinologist and cancer researcher and has been a key scientist in understanding the biology of estrogen receptors and in elucidating mechanisms by which antiestrogens and SERMs, such as Tamoxifen and Raloxifene, are effective in controlling breast cancer. The work of her research group has most recently involved the development of selective hormonal agents for breast cancer treatment and prevention.

The quality and impact of Professor Katzenellenbogen's scholarly achievements are extraordinary. Since joining the faculty of the University of Illinois in 1971, she has published over 250 research articles, has contributed 30 chapters in books, and has co-edited a text on hormone-dependent cancers.

She is the recipient of numerous awards, honors and special fellowships from governmental, private and academic institutions including the MERIT Award (1991-1999) from the National Cancer Institute at the National Institutes of Health, the Jill Rose Award for outstanding research from The Breast Cancer Research Foundation, the Ernst Oppenheimer Award and Roy O. Greep Lecture Award of The Endocrine Society, the Distinguished Scientist Award from the Susan G. Komen Breast Cancer Foundation, and the National Scholar Award from the American Association of University Women.

She is a Fellow of the American Academy of Arts and Sciences and recently served as President of The Endocrine Society, the world's largest professional society representing approximately 10,000 endocrinologists. She has been active on government scientific review panels of the National Institutes of Health and the American Cancer Society, and has served on the editorial boards of several scientific journals. She directs an active research unit that has trained over 70 graduate students and postdoctoral scientists, many of whom are leading distinguished careers in academia, governmental agencies, and the pharmaceutical/biotechnology industry.