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Benita S. Katzenellenbogen, PhD
Departments of Molecular and Integrative Physiology
Cell and Developmental Biology
University of Illinois at Urbana-Champaign
Goal: To identify targets for the development of drugs that would prevent drug resistance and improve breast cancer outcomes.
Impact: Dr. Katzenellenbogen is developing potential drugs that block a protein called FOXM1, a driver of breast cancer progression, drug resistance, and metastasis. Her efforts may lead to the development of treatments that restore sensitivity to endocrine therapies or chemotherapies in patients whose tumors no longer respond to these drugs.
What’s next: She and her team will explore the anti-tumor activity of FOXM1 inhibitors they’ve developed in both primary tumors and metastases. They will also examine how well each compound is able to prevent metastasis.
Dr. Katzenellenbogen has shown that blocking a protein, FOXM1, can restore sensitivity to endocrine therapies or chemotherapies—an important discovery given that estrogen-driven breast tumors can develop resistance to these therapies. She and her colleagues have identified a new class of FOXM1 inhibitors that may enhance the effectiveness of endocrine and chemotherapies.
Full Research Summary
Research area: Developing alternative treatments for patients whose tumors no longer respond to anti-estrogen therapies.
Impact: Estrogen-driven breast cancer (ER-positive) is the most common subtype of breast cancer and is treatable with anti-estrogen (endocrine) therapies such as tamoxifen and aromatase inhibitors. However, many of these tumors become resistant to endocrine therapies, which allows them to grow and metastasize (spread to other tissues). Dr. Katzenellenbogen has been studying the protein, FOXM1, which plays a role in breast cancer progression, resistance to endocrine and other cancer therapies, and metastasis. Her findings may inform the development of treatments for aggressive breast cancers.
Current investigation: Dr. Katzenellenbogen and her colleagues have been working to identify potent and effective drugs that block FOXM1. These treatments may also benefit patients with triple-negative breast cancer (TNBC).
What she’s learned so far: Dr. Katzenellenbogen found that FOXM1 is markedly elevated in breast cancers when they become resistant to endocrine therapies and chemotherapies. Her work has shown that FOXM1 regulates gene networks and signaling pathways that promote expansion of cancer stem cells that underlie the resistance to cancer treatments. Her team has optimized FOXM1 inhibitors that suppress tumor growth.
What’s next: They will now study how FOXM1 inhibitors suppress both primary tumor growth and metastasis. In addition, they will explore which whether FOXM1 inhibitors can be combined with currently used drugs, such as tamoxifen or paclitaxel, to best prevent the progression of aggressive breast cancer.
Benita Katzenellenbogen is Swanlund Professor of Physiology, Cell and Developmental 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, she has published over 350 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, Roy O. Greep Lecture Award, and Koch Lifetime Achievement 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 previously 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 approximately 100 graduate students and postdoctoral and visiting scientists.