Department of Molecular and Integrative Physiology
Cell and Structural Biology
University of Illinois at Urbana-Champaign
Area of Focus: Metastasis, Treatment and Tumor Biology
- Seeking new therapeutic targets for the development of drugs to prevent drug resistance and improve breast cancer outcomes.
- Laboratory studies are focused on the development of drugs to block a protein called FOXM1 as a strategy to improve response to anti-estrogen therapies.
- These efforts have the potential to deliver more powerful anti-estrogen drugs to patients whose tumors have become resistant to these therapies.
Most breast cancers require estrogen to grow. While 5-year prognosis of early stage, estrogen-driven breast cancers (called ER-positive) is very good, late recurrence and resistance to anti-estrogen therapies reduce overall survival for many patients. Dr. Katzenellenbogen is developing alternative therapeutic approaches to benefit women whose tumors no longer respond to anti-estrogen therapy.
Full Research Summary
Estrogen-driven breast cancer (ER-positive) is the most common breast cancer and is treatable with anti-estrogen (endocrine) therapies, such as tamoxifen and aromatase inhibitors. In spite of excellent treatment options and good prognosis, many tumors acquire resistance to these therapies and continue to grow or spread to other tissues, a process called metastasis.
The Katzenellenbogen lab has shown that resistance to endocrine therapies and breast cancer aggressiveness are associated with up-regulation and overexpression of the protein FOXM1.
Dr. Katzenellenbogen’s team has shown that blocking FOXM1 can restore sensitivity to endocrine therapies or chemotherapies. Although drugs exist to target this protein, there are several limitations to their clinical use.
The research group has successfully identified a new class of FOXM1 inhibitors that are potent and effective in blocking FOXM1 actions and tumor growth. They will now expand their studies to examine the ability of these new inhibitors to prevent metastasis. They will also evaluate the the ability of these inhibitors to synergize with current standard-of-care treatments to enhance the suppression of breast cancer growth and tumor invasiveness using laboratory models of breast cancer.
These approaches should enhance the effectiveness of endocrine therapies, as well as other chemotherapies, and reduce the risk of recurrence for many breast cancer patients.
Benita Katzenellenbogen is Swanlund Professor of Physiology, Cell and Structural Biology, and director of a breast cancer research group at the University of Illinois 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.
Since joining the University of Illinois in 1971, she has published over 250 research articles, contributed 30 chapters in books, and co-edited a text on hormone-dependent cancers. She is the recipient of numerous awards and honors from governmental and private institutions including the MERIT Award (1991-1999) from the National Cancer Institute, Jill Rose Award from The Breast Cancer Research Foundation, Ernst Oppenheimer Award and Roy O. Greep Lecture Award of The Endocrine Society, Distinguished Scientist Award from the Susan G. Komen Breast Cancer Foundation, and 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. 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. The research unit she directs has trained over 70 graduate students and postdoctoral scientists.