Titles and Affiliations
Professor, Department of Pathology
Research area
Discovering ways to improve treatment response in patients with estrogen receptor-positive breast cancer.
Impact
Breast cancers that are driven by estrogen—called estrogen receptor (ER)-positive—have the best five-year prognosis of any breast cancer. Despite effective therapies to treat ER-positive breast cancer, one-quarter to one-third of patients will experience a breast cancer recurrence. Outcomes for advanced ER-positive breast cancer have improved substantially, especially for patients whose metastatic disease is limited to bone, thanks to newer treatments that overcome early drug resistance. However, most patients eventually develop endocrine resistance, allowing cancer cells to spread to multiple organs throughout the body. Dr. Sartorius’ research asks what features of this resistance allow tumors to survive therapy and spread, and how these features might be targeted therapeutically—a question increasingly urgent as more women live longer with advanced ER-positive disease.
Progress Thus Far
Over the past year, Dr. Sartorius and her team made progress in uncovering how certain breast cancers become resistant to hormone (endocrine) therapies and continue to grow and spread. They focused on two key molecular pathways that help resistant cancer cells survive. First, the team found that levels of an enzyme called FADS2 and its activity are much higher in endocrine-resistant breast cancer cells than in treatment-sensitive ones, and that these resistant cells depend on FADS2 to survive. When they reduced FADS2 levels, resistant cells stopped growing, while normal cells were unaffected. The team traced this dependency to the observation that resistant cells begin producing their own polyunsaturated fatty acids, molecules typically linked to anticancer activity, and that disrupting how resistant cells make them can trigger cancer cell death.
In parallel, the team found that endocrine-resistant tumors efficiently release circulating tumor cells (CTCs) into the bloodstream, and that these CTCs interact closely with blood cells in ways that may help cancer cells survive the physical stresses of circulation.
What’s next
In the coming year, Dr. Sartorius and her team will investigate in greater depth how CTCs interact with blood cells to survive in the bloodstream and go on to establish further metastases. They will also determine precisely how endocrine-resistant breast cancer cells process and store their polyunsaturated fatty acids and test further whether disrupting these pathways can reliably and selectively trigger cancer cell death. Together, these studies aim to identify new therapeutic strategies to prevent the progression of ER-positive breast cancer.
Biography
Carol A. Sartorius, PhD earned her bachelor’s degree from the University of Michigan and PhD from the University of Colorado Health Sciences Center, both in Molecular Biology. She did her postdoctoral work at the University of Colorado Boulder and is currently a Professor of Pathology at the University of Colorado Anschutz Medical Campus (UC-AMC).
Dr. Sartorius’s research studies the biology, progression, and endocrine resistance of hormone receptor positive breast cancer. Her laboratory seeks to understand the molecular basis of transcriptional regulation by progesterone receptors (PR) and how this impacts estrogen receptors (ER) and tumor cell phenotype. Current research topics include hormone regulation of cancer stem cells and tumor heterogeneity, hormone regulation of metastasis, hormone control of translation and protein synthesis, and how host obesity and metabolic syndrome specifically affect ER-positive breast cancer and endocrine resistance. Dr. Sartorius’s team also specializes in developing hormone-dependent breast cancer models. She is the co-founder and co-director (with Dr. Peter Kabos) of the breast cancer patient-derived xenograft (PDX) bank at UC-AMC. Their collection emphasizes ER and PR-positive tumors. These tumor models are being characterized by genomic and proteomic techniques to discover novel hormone receptor interactions that can be leveraged for treatment. The goal is to improve hormone-directed therapies for breast cancer.
She is an active member of the Cancer Biology Training Program at UC-AMC with an interest in training the next generation of scientists in the field of hormones and cancer. Her laboratory trains predoctoral students, and postdoctoral and clinical fellows.
