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. The goal of Dr. Sartorius’ BCRF research is to identify and test vulnerabilities in a common but understudied group of cells in ER-positive tumors that are ER-negative. This population of cells may be responsible for drug resistance and recurrence and behaves like cancer stem cells, which can initiate and drive cancer progression. By understanding how these cells promote tumor growth and identifying their weaknesses, she hopes to identify strategies to turn them off and prevent recurrence.
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. In parallel, they discovered that a surface protein called SDC2 is also enriched in resistant breast cancer cells. This protein helps cells adhere to their surroundings and interact with blood components, potentially aiding metastasis. The team explored this by reducing SDC2 levels in fulvestrant-resistant breast cancer cells and found reduced metastases in a model system. Finally, the team has begun to study a key ER mutation to better understand how this mutation fuels resistance and whether restoring ER function can re-sensitize tumors to hormone therapy.
What’s next
In the coming year, Dr. Sartorius and her team will build on their work understanding how FADS2 and SDC2 help breast cancers resist hormone therapy and spread. They will study how FADS2 supports cancer cell survival and test whether blocking FADS2 activity can make tumors more vulnerable. They will use gene editing tools to precisely turn off SDC2 in hormone? resistant cancer models and test whether a small peptide can block its activity. They will also explore how SDC2 helps cancer cells stick to platelets in the blood, a step that may help them travel and form metastases. Finally, they will create new cell models to compare hormone-sensitive and resistant tumors, helping the team to pinpoint how specific gene mutations drive resistance and identify new ways to overcome it.
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.
