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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: Dr. Katzenellenbogen has been developing compounds that may inhibit the growth and spread of breast tumors in patients who have estrogen receptor (ER)-positive breast cancer. His efforts may lead to the development of powerful anti-estrogens that will prevent recurrence of ER-positive breast cancers.
What’s next: He and his colleagues are studying a form of the estrogen receptor called ER-beta (ERβ), found in some triple negative breast cancers (TNBCs). Dr. Katzenellenbogen plans to use new hormone agents and antibodies he and his team have developed that are specific for ERβ to determine whether 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 the 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: Approximately one third of ER-positive metastatic breast cancers contain mutated forms of the estrogen receptor that are continuously “turned on” and thus more difficult to treat with current anti-estrogen drugs such as tamoxifen or fulvestrant. Dr. Katzenellenbogen is pursuing new treatments that would prevent the growth and spread of breast cancers with these mutations.
In addition, he is investigating a less common form of the estrogen receptor, ERβ—found in many TNBCs—in order to determine whether it may be a useful target for new therapies for this aggressive form of breast cancer.
His efforts could lead to more effective ways of treating patients who have recurrent ER-positive breast cancer and 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 triple negative breast cancers that often harbor this form of the estrogen receptor.
What he’s learned so far: Dr. Katzenellenogen’s team has developed new anti-estrogen agents that potently and effectively inhibit the growth of ER-positive breast cancer cells and tumors that have mutations in the estrogen receptor. They have shown that these new drugs can suppress breast cancer metastasis and extend survival in preclinical models of breast cancer.
What’s next: Dr. Katzenellenbogen will conduct laboratory tests of both the ERβ-selective compounds and antibodies he and his team have developed.
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, and Portoghese Medicinal Chemistry Lectureship Award from 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.