Benita S. Katzenellenbogen, PhD

Approximately 70% of breast cancers are positive for estrogen receptor at diagnosis, and these patients often benefit from endocrine therapies, either treatment with antiestrogens such as tamoxifen or aromatase inhibitors such as letrozole, which block estrogen stimulation of these cancers by inhibiting the estrogen receptor. The effectiveness of endocrine therapies is often lost with time, however, because the tumor cells become resistant. Dr. Katzenellenbogen and her research group have shown that effective endocrine therapy involves integration of estrogen receptor actions both in the nucleus and outside of the nucleus of breast cancer cells, and that resistance involves increased activity of kinases and growth factors that work along with the protein 14-3-3ζ(zeta) to increase tumor cell growth and survival. Preliminary studies indicate that high levels of the 14-3-3ζ protein are associated with tumors that show a poor clinical outcome on endocrine therapy. Further, high levels of this protein bypass the blockade of estrogen receptor action by endocrine therapies. These results suggest that targeting 14-3-3ζ could be a useful approach for enhancing and prolonging the effectiveness of endocrine therapies.

In the year ahead, the researchers will examine the levels and subcellular distribution of this protein in human breast tumors as a marker of tumor aggressiveness and loss of endocrine responsiveness, and will explore ways to inhibit the activity of 14-3-3ζ in order to maintain or restore sensitivity to endocrine therapies. The hope is that blocking the action of 14-3-3ζ and the kinases whose activity it supports, would prove to be a new approach to improving endocrine sensitivity in breast cancer, thereby making endocrine therapies more effective for many breast cancer patients.

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.