For decades, the estrogen receptor (ER) has been the primary target in the treatment of ER-positive/luminal breast cancers. Drugs that block ER transcriptional activity and/or degrade ER or halt estrogen synthesis have been used to treat a majority of patients with ER positive breast cancers.
“These treatments are initially highly effective, but recurrence of metastatic disease remains a significant clinical challenge,” said Carol Lange, PhD, Professor of Medicine and Pharmacology, Tickle Family Land Grant Endowed Chair of Breast Cancer Research, and Associate Director of Basic Science at the Masonic Cancer Center at the University of Minnesota. “For advanced breast cancer, endocrine therapies are often combined with protein kinase inhibitors, such as drugs directed against HER2 or CDK4/6, but with limited success for a majority of women.”
Dr. Lange will moderate the Basic Science Forum, Targeting Nuclear Steroid Receptors, on Wednesday, December 8. She will be joined by a panel of investigators who will discuss the potential for targeting, or co-targeting with endocrine therapy, other steroid hormone receptors that are often co-expressed with or instead of ER.
“This is important because alternate, or non-ER, steroid hormone receptors represent a largely untapped class of molecules that may either contribute to or block breast cancer development and progression and interact with ER in complex ways,” Dr. Lange said. “Understanding their roles in breast cancer and how and when they cross talk with ER may lead to new ways to prolong life and longevity of women with ER-positive breast cancer.”
Wayne Tilley, PhD, Professor and Director of the Dame Roma Mitchell Cancer Research Laboratories at the University of Adelaide in Australia, will discuss androgen receptor (AR) action in ER-positive breast cancer, including the protective role of AR expression and how activation, rather than inhibition, of AR can be employed to improve outcomes.
Christy Hagan, PhD, Associate Professor of Biochemistry and Molecular Biology at the University of Kansas Medical Center, will talk about the role of progesterone and the progesterone receptor (PR) in breast cancer biology and treatment, and how recent advances have shown that progesterone/PR promotes cancer cell survival and shields ER-positive breast tumor cells from the surveilling immune system.
Suzanne Conzen, MD, Professor in the Department of Internal Medicine and Chief of the Division of Hematology and Oncology at UT Southwestern Medical Center, will review current understanding of how glucocorticoid receptor (GR)-mediated signaling pathways influence triple-negative (lacking both ER and PR, as well as amplification of HER2) and ER-positive breast cancer progression, and how GR activity can be modulated to alter breast cancer biology.
“At the end of this forum, I expect audience members to have a much stronger picture of the molecular and hormonal landscape of breast cancer with regard to steroid hormone receptor expression, actions, and interactions, and how this new information may be leveraged to improve clinical outcomes, largely with drugs we already have,” Dr. Lange said. “The science and the new evidence emerging in this area is really exciting because it can be rapidly translated into improved treatments that will impact women’s health.”