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John Katzenellenbogen, PhD
Swanlund Professor of Chemistry
University of Illinois at Urbana-Champaign
Goal: To develop new ways to prevent resistance to anti-estrogen therapies and extend the lives of breast cancer patients.
Impact: About one third of metastatic breast cancers that are estrogen receptor (ER)-positive contain mutations in this receptor that make the cancer resistant to hormone therapies. Dr. Katzenellenbogen has been developing compounds that may inhibit the growth and spread of these breast tumors. His efforts may lead to the development of powerful anti-estrogens that will prevent recurrence of ER-positive breast cancers. His team is now examining the second estrogen receptor, named ERβ, which is found in many triple-negative breast cancers and evaluating the potential of ERβ as a therapeutic target for this difficult-to-treat and aggressive subtype of breast cancer.
What’s next: He and his colleagues have developed new hormone agents and antibodies which are specific for ERβ and will determine if ERβ could be a target for new forms of hormone therapy.
Many breast cancers can be successfully treated with anti-estrogen (endocrine) therapies that target the estrogen receptor (ER). However, these breast cancers sometimes recur with mutations in ER that make them resistant to endocrine therapy. Dr. Katzenellenbogen has been investigating how these altered receptors work and has developed new anti-estrogens that may be able to treat breast tumors that harbor these mutations.
Full Research Summary
Research area: Developing drugs that will stop the growth of recurrent ER-positive and triple-negative (TNBC) breast cancers.
Impact: Many breast cancers are hormone receptor positive and can often be treated successfully with targeted hormone therapies that block the actions of the receptors that are driving these cancers. A significant fraction of breast cancers, however, lack these receptors and are termed triple-negative breast cancer (TNBC). TNBC is difficult to treat with a high likelihood for recurrence. While TNBC lacks estrogen receptor alpha (ERα), which is the major target for hormone therapies in ER-positive breast cancers, most TNBCs contain estrogen receptor beta (ERβ). Dr. Katzenellenbogen is evaluating ERβ as a potential target for treating TNBC. Using antibodies and new compounds specific for ERβ, Dr. Katzenellenbogen and his team will determine whether targeting ERβ might be effective and beneficial for treating women with TNBC.
Current investigation: Dr. Katzenellenbogen has been developing new types of anti-estrogens that will be effective against breast cancers that no longer respond to the standard anti-estrogen therapies. He is also extending his work to study ERβ-selective compounds for treatment of TNBCs that often harbor this form of the estrogen receptor.
What he’s learned so far: Dr. Katzenellenbogen team has developed new anti-estrogen agents (selective estrogen receptor modulators, SERMs) that potently and effectively inhibit the growth of ER-positive breast cancer cells and tumors that have mutations in the estrogen receptor. In preclinical studies, they have shown that these SERMs inhibit the proliferation, growth, and metastasis of breast tumors suggesting that they are promising for further development. In preparation for other studies to evaluate ERβ as a potential therapeutic target for TNBC tumors, his team has developed several ERβ-selective compounds and antibodies. They have characterized 5 isoforms of ERβ and shown that ERβ2 and ERβ5 stimulate oncogenic and invasive features of TNBC cells and ERβ1 suppresses these features.
What’s next: Dr. Katzenellenbogen and his team will analyze the levels and activities of the different forms of ERβ that are present in TNBC and will focus on ERβ1 that appears to reduce the growth of TNBC cells and tumors thereby slowing their metastatic spread. They hope to develop new strategies to treat TNBC which could reduce the need for chemotherapy and improve outcomes for these patients.
Dr. John Katzenellenbogen, Swanlund Professor of Chemistry, directs a research program at the University of Illinois at Urbana-Champaign that spans chemistry, biology, and medical applications with a particular focus on the action of estrogens in breast cancer. He is recognized internationally as a pioneer in the development of novel diagnostic and therapeutic agents for the management of hormone-regulated cancers, including the PET imaging agents FES for estrogen receptors in breast cancers and FDHT for androgen receptor in prostate cancers, both of which are widely used in the clinical development of novel anti-hormonal agents. Through his extensive work elucidating the molecular details of estrogen action in various target tissues, he has designed novel estrogens that are being actively used to elucidate estrogen actions by numerous collaborators throughout the world.
Dr. John Katzenellenbogen has been honored as a Fellow of the American Academy of Arts and Sciences on whose National Council he served for many years, he is the recipient of the Paul Aebersold Award from the Society of Nuclear Medicine, the E. B. Hershberg Award for Important Discoveries in Medicinal Chemistry, the Esselen Award for Chemistry in the Public Service, the Portoghese Medicinal Chemistry Lectureship Award, and induction into the Medicinal Chemistry Hall of Fame of the American Chemical Society, The Royal Society of Chemistry Centenary Award, the Leading Edge Award from the Society of Toxicology, and with Dr. Benita Katzenellenbogen the Fred Conrad Koch Lifetime Achievement Award from the Endocrine Society. He has trained more than 100 doctoral students and postdoctoral fellows, and he has published more than 500 articles.
BCRF Investigator Since
The Ulta Beauty Award